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Biomedical subjects

A Jaeger

Publications and source records attributed to A Jaeger.

At least 19 recordsLinked to original sources

Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.

UNLABELLED: We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia-euglycemia clamp, rats in glucose-insulin-digoxin (GID) group (n=10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n=10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p<0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15+/-12min whereas in GID group the survival period was significantly increased to 38+/-3min (p<0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p<0.001). Animal death occurred after a digoxin infusion volume of 7.7+/-0.6ml and 3.0+/-2.4ml in GID and digoxin group respectively (p<0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1+/-2mmol/l versus 4.4+/-0.4mmol/l (p<0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137+/-40min whereas death of rats in the digoxin group occurred within 80+/-10min (p<0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9+/-0.5mmol/l versus 4.9+/-0.3mmol/l (p<0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7+/-1.6ml versus 3.3+/-0.4ml (p<0.001) and 10.7+/-8.3mg/l versus 8.5+/-4.6mg/l. CONCLUSION: Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity.

Animals↗

Mutually dependent secretion of proteins required for mycobacterial virulence.

The ESX-1 locus is a region critical for full virulence in Mycobacterium tuberculosis, which encodes two secreted proteins as well as other genes involved in their secretion. The mechanism of secretion of the two proteins, ESAT-6 and CFP-10, and their function remain unknown. Using proteomic methods to search for additional proteins secreted by the ESX-1 locus, we discovered that a protein encoded by a chromosomally unlinked gene, espA, is also secreted by strains that contain the ESX-1 locus but not by strains with ESX-1 deletions. Mutations in individual ESX-1 genes, including those that encode ESAT-6 and CFP-10, were found to block EspA secretion. Surprisingly, mutants that lack espA reciprocally failed to secrete ESAT-6 and CFP-10 and were as attenuated as ESX-1 mutants in virulence assays. The results indicate that secretion of these proteins, which are each critical for virulence of pathogenic mycobacteria, is mutually dependent. The results further suggest that discerning the nature of the interaction and the structure of macromolecular complexes will provide insights into both an alternative mechanism of protein secretion and mycobacterial virulence.

Animals↗

[Spontaneous anaerobic osteomyelitis with necrotizing fasciitis of femur: two reasons for the use of hyperbaric oxygenotherapy].

This is a case report of a 50-year-old male patient who had septic shock with anaerobic bacterial septicaemia coming from a spontaneous left femoral osteomyelitis. The combined treatment with antibiotics, surgery and hyperbaric oxygenotherapy restored normal mobility of the lower limb. Two years later, there was no recurrence. Despite many efforts the aetiology of the disease is unknown. The authors, discuss the relevance of hyperbaric oxygenotherapy in such cases.

Anti-Bacterial Agents↗

Rationales of arthroscopic shoulder stabilization.

Arthroscopic reconstruction of glenohumeral instability has become more common during the past decade. Compared with open reconstruction, which is still the gold standard in the treatment of shoulder instability, arthroscopic techniques allow for improved diagnosis of numerous intraarticular findings. This review presents an appropriate system for the arthroscopic classification of most pathological findings in patients with anterior shoulder instability. Based on the presented classification, a rationale for arthroscopic reconstruction under special conditions is given. Several operative techniques and implants are discussed and their use in certain circumstances analyzed. Special emphasis is targeted on techniques of realizing sufficient capsular shift or plication. Arthroscopic procedures remain technically demanding and require skills to address the great variety of possible situations. On the other hand, arthroscopic techniques in shoulder reconstruction benefit patients by avoiding the morbidity of open surgery. However, the surgeon must be prepared to address numerous conditions beyond a mere Bankart lesion, especially those involving capsular laxity, rotator interval lesions, and SLAP (superior labrum lesions from anterior to posterior) lesions. Nowadays, considering all the new technical possibilities of arthroscopic shoulder reconstruction including capsular shift procedures, most cases of anterior shoulder instability are suitable for arthroscopic reconstruction. Further studies are necessary to validate the continued efficacy of arthroscopic stabilization.

Arthroscopy↗

Fatal allergic vasculitis associated with celecoxib.

We report on the occurrence of a rare and as yet unforseeable adverse reaction to treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective, non-steroidal, anti-inflammatory drug. A previously healthy adult suffered fatal acute multiple organ failure presumably after diffuse allergic vasculitis with diffuse necrotic purpura. Although no conclusive proof is available, such a reaction could have been triggered by at least one of two mechanisms: an allergic reaction linked to the chemical structure of celecoxib; or an interaction of the drug with synthesis of endothelial eiconasoids leading to an imbalance between vasoactive end products, resulting in widespread rise to local thrombosis.

Anti-Inflammatory Agents, Non-Steroidal↗

An experimental ecotoxicological study and its application to the behavioural study of organic mercury (CH3HgCl) in the environment: influence of temperature and pH.

Laboratory experiments were carried out to study the influence of temperature (24, 28 and 30 degrees C) and pH (1-10) on organic mercury (CH3HgCl) transfer and accumulation in an experimental ecotoxicological model. We followed the evolution of CH3HgCl in a basic model (water + air) by varying temperature and pH. In a second step, we completed the model by adding sediment and fish. We added CH3HgCI to water at the beginning of each experiment which was repeated at least three times. Results demonstrated that mercury was released from methylmercury into the air regardless of water pH and its concentration in the air increased with increasing pH. By contrast, in presence of sediment, almost all the mercury was fixed onto the sediment and no mercury was traced in air or in water. Interestingly, in the presence of sediment, the life span of fish under methylmercury exposure lasted longer despite their higher mercury body level content at their death. These results indicate that water is a bad exposure indicator for aquatic pollution. In case of chronic pollution, sediments, fish and aquatic plants are more appropriate indicators.

Animals↗

Treatment of acute methanol poisoning with fomepizole.

OBJECTIVE: To assess the efficacy and safety of fomepizole, a competitive alcohol dehydrogenase inhibitor, in methanol poisoning and to test the hypothesis that fomepizole obviates the need for hemodialysis in selected patients. DESIGN AND SETTING: Retrospective clinical study in three intensive care units in university-affiliated teaching hospitals. PATIENTS: All methanol-poisoned patients admitted to these ICUs and treated with fomepizole from 1987-1999 (n=14). MEASUREMENTS AND RESULTS: The median plasma methanol concentration was 50 mg/dl (range 4-146), anion gap 22.1 mmol/l (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate 17.5 mmol/l (3.0-25.0). Patients received oral or intravenous fomepizole until blood methanol was undetectable. The median cumulative dose was 1250 mg (500-6000); the median number of twice daily doses was 2 (1-16). Four patients underwent hemodialysis for visual impairment present on admission. Four patients with plasma methanol concentrations of 50 mg/dl or higher and treated without hemodialysis recovered fully. Patients without pretreatment visual disturbances recovered, with no sequelae in any case. There were no deaths. Fomepizole was safe and well tolerated, even in the case of prolonged treatment. Analysis of methanol toxicokinetics in five patients demonstrated that fomepizole was effective in blocking methanol's toxic metabolism. CONCLUSIONS: Fomepizole appears safe and effective in the treatment of methanol-poisoned patients. If our results are confirmed in prospective analyses, hemodialysis may prove unnecessary in patients presenting without visual impairment or severe acidosis.

Adolescent↗

Repeated measurements of aldicarb in blood and urine in a case of nonfatal poisoning.

A nonfatal case of poisoning involving aldicarb, an extremely toxic carbamate pesticide, is presented. A 39-year-old female ingested an unknown amount of aldicarb, together with alprazolam and sertraline. On admission to ICU (T0), she displayed marked cholinergic symptoms and a deep coma. The patient was given pralidoxime and atropine. Her condition gradually improved on days 2 and 3 and she was discharged at T0+80 h. Aldicarb was assayed by high-performance liquid chromatography on 21 blood and 8 urine samples successively taken during hospitalization. At the same time, serum pseudocholinesterase activity was followed on 21 successive samples. Blood aldicarb level was 3.11 microg/mL at T0 and peaked at T0+3.5 h (3.22 microg/mL), then followed a two-slope decay with a terminal half-life of ca. 20 h. Aldicarb was detected in all urine samples (peak level: 6.95 microg/mL at T0+31.5 h) and was still present at the time of discharge. Serum pseudo-cholinesterase activity remained low (< or = 10% of normal) until the 30th hour then rapidly increased and returned to normal after the 60th hour. The patient's clinical picture closely followed blood aldicarb levels and serum pseudo-cholinesterase activities. To our knowledge, this is the first report of an aldicarb poisoning documented by repeated measurements of the drug in the intoxicated person.

Adult↗

[Complications of difficult tracheal intubations in a critical care unit] .

OBJECTIVES: This study was performed in order to evaluate the frequency of DI, the predictive factors of DI and to list the related complications. STUDY DESIGN: Prospective non randomized, open study. PATIENTS AND METHODS: All patients intubated in the critical care unit during the five months of the study were included. The previous history and clinical setting of the patients, the conditions and the complications of intubation were collected. DI was defined when the procedure required more than two laryngoscopies. RESULTS: The study included 80 patients. The rate of DI was 22.5%. The Mallampati score (p < 0.001) was the only predictive factor. The frequency of complications was 25%. This rate was 55% for DI versus 16% for easy intubations (p < 0.001). CONCLUSION: This study confirms the high incidence of DI and associated complications in critical care. We suggest the development of airway management protocols in critical care unit in order to reduce the rate of DI.

Adult↗

Noninvasive pressure support ventilation (NIPSV) with face mask in patients with acute cardiogenic pulmonary edema (ACPE)

OBJECTIVES: To assess (1) the short-term hemodynamic, respiratory and arterial blood gas effects of NIPSV in patients with ACPE who were likely to require endotracheal intubation, (2) the initial causes of failure and (3) the side effects and the difficulties of this technique. DESIGN: Uncontrolled, prospective clinical study. SETTING: Teaching hospital intensive care unit. PATIENTS: 26 consecutive patients with severe ACPE. INTERVENTIONS: Noninvasive ventilation via a face mask, using a pressure support mode (20.5+/-4.7 cm H2O), with an initial fractional inspired oxygen of 93.0+/-16% and a positive end-expiratory pressure of 3.5+/-2.3 cm H2O. The need to intubate the patients within 48 h was considered as a criterion of failure of the procedure. MEASUREMENTS AND RESULTS: Clinical and biological parameters were measured at 15 and 30 minutes, 1 h and 2 h and at 1 h and 2 h, respectively. There were 5 (21%) failures and 21 (79%) successes. In both the success and the failure groups, clinical and blood gas parameters improved at the first measure. In the success group, within 15 min of the start of NIPSV, pulse oximetry saturation (SpO2) had increased from 84+/-12 to 96+/-4% (p<0.001), the respiratory rate (RR) had decreased from 36+/-5.3 to 22.4+/-4.9 breaths/ min (p<0.0001) and within 1 h the arterial oxygen tension and pH, respectively, had increased from 61+/-14 to 270+/-126 mm Hg (p<0.0001) and from 7.25+/-0.11 to 7.34+/-0.07 (p<0.01) and the arterial carbon dioxide tension (PaCO2) had decreased from 54.2+/-15 to 43.4+/-6.4 mm Hg (p<0.01). There were no statistical differences between the success and failure groups for the initial clinical parameters: SpO2, RR, heart rate, mean arterial pressure. The only differences between the success and failure groups were in the PaCO2 (54.2+/-15 vs. 32+/-2.1 mm Hg, p<0.001) and the creatine kinase (CPK) (176+/-149 vs. 1282+/-2080 IU/l, p<0.05); this difference in CPK activity was related to the number of patients who had an acute myocardial infarction (AMI) (4/5 in the failure group vs. 2/21 in the success group, p<0.05). All patients with AMI in the failure group died. CONCLUSION: Among patients in acute respiratory failure, those with severe ACPE could benefit from NIPSV if they are hypercapnic, but NIPSV should be avoided in those with AMI.

Acute Disease↗

Are kinetic investigations feasible in human poisoning?

Kinetics in human poisoning have gained more importance because of the development of specific and quantitative analytical methods. Despite many pitfalls related to unprecise data in acute poisonings, several studies showed that kinetic parameters, determined by a simple approach, may be helpful for the management. Parameters include plasma elimination half-life, total, renal and hepatic clearances, amounts eliminated by normal routes or by specific treatments. For numerous drugs, spontaneous toxicokinetics and factors of variation could be assessed. These include the dose ingested, the type of poisoning, the age; the symptoms and organ failures; the associated drugs. Kinetic studies have been a major step for the evaluation of treatments such as gastric lavage, oral activated charcoal, haemodialysis, antidotes and have contributed to the understanding of kinetics-dynamics relationships and to the assessment of severity and prognosis criteria. In clinical practice, it is possible by kinetic investigations to select the patients which will really benefit from a treatment such as haemodialysis in lithium poisoning.

Humans↗

[Acute poisoning during substitution therapy based on high-dosage buprenorphine. 29 clinical cases--20 fatal cases].

OBJECTIVES: Buprenorphine has been an important advance in care for drug abusers, but the toxic risk may be fatal. We report here two original series of buprenorphine poisoning in opiate abusers on substitution therapy. PATIENTS: The first series included 20 males and 9 females, aged 20-35 years (mean = 27.5) with non-fatal poisoning. The second series included 20 subjects (19 males, 1 female) aged 14-48 years (mean = 26.6) with a fatal outcome. All subjects were opiate addicts taking high-dosage sublingual buprenorphine formulation as substitution therapy. RESULTS: Blood concentrations of buprenorphine were found in all cases to remain at a low level (1.0-2.3 ng/ml, m = 1.4 ng/ml, and 1.1-29.0 ng/ml, m = 8.4 ng/ml in non-fatal and fatal cases respectively). Almost all cases involved concomitant intake of psychotropic medications, especially benzodiazepines (18 non-fatal and 17 fatal cases). DISCUSSION: These observations confirm previously reported data on the danger of buprenorphine-benzodiazepine combinations. Intravenous injection of crushed tablets also appears to be a risk factor (8 deaths and 10 non-fatal poisonings). This series highlights the need for improvement in the recently developed French program for substitution therapy with high-dosage buprenorphine in heroin addicts.

Administration, Sublingual↗

Modelling of phospholipid translocation in the erythrocyte membrane: a combined kinetic and thermodynamic approach.

A mathematical model for the dynamics of transbilayer movements of lipids in the erythrocyte plasma membrane is presented. It takes into account an active carrier which mediates the ATP-dependent translocation of phosphatidylserine and phosphatidylethanolamine from the outer to the cytoplasmic leaflet of the membrane and passive fluxes of these lipids as well as of phosphatidylcholine, sphingomyelin and cholesterol between both layers. It is assumed that the passive fluxes are driven by concentration gradients of the lipids and by mechanical forces which result from area limitation for lipid occupation in both leaflets. Compared with a previous mathematical treatment of lipid translocation processes in the erythrocyte membrane the present model is much closer to realistic conditions, e.g. concerning the number of lipid species involved. Furthermore, the use of linear flux-force relationships as known from irreversible thermodynamics allows a simpler treatment of the passive fluxes than before and provides a relevant framework to study the coupling between the various processes. The model allows to simulate the time dependent changes of lipid concentrations which take place after activation or inhibition of ATP-dependent translocation. Using realistic parameter values it explains in quantitative terms the stationary asymmetric distribution of lipids under in vivo conditions. Using principles of metabolic control analysis we are able to quantify the role of the various active and passive processes in determining the asymmetric distribution for each lipid species.

Animals↗

[Acute poisoning by class I anti-arrhythmia agents and by chloroquine].

Poisonings with class I antiarrhythmic drugs and chloroquine are characterized by their severity, related to their membrane-stabilizing effect. Because of the rapid onset of severe cardiovascular disturbances with circulatory arrest, cardiogenic shock, conduction abnormalities, ventricular dysrhythmia, rapid hospitalisation in an intensive care unit is mandatory with continuous monitoring of electrocardiogram, blood pressure and biological variables. Treatment includes mechanical ventilation, inotropic agents, especially epinephrine, hypertonic sodium salts, and diazepam in case of chloroquine poisoning.

Acute Disease↗

Invasive pulmonary aspergillosis with cerebromeningeal involvement after short-term intravenous corticosteroid therapy in a patient with asthma.

The present case report describes a case of invasive pulmonary aspergillosis with cerebromeningeal invasion in an asthmatic non-immunocompromised patient. This fatal complication occurred despite early anti-fungal antibiotherapy after a 2-week course of intravenous corticosteroid therapy for treatment of an exacerbated asthma. Diagnostic and therapeutic procedures are discussed.

Aged↗