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Biomedical subjects

E Segal

Publications and source records attributed to E Segal.

At least 37 records · Page 2Linked to original sources
PubMed2001

Recombinant activated factor VII for adjunctive hemorrhage control in trauma.

BACKGROUND: Recombinant activated factor VII (rFVIIa) was approved for treatment of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII or IX. Conditions with increased thromboembolic risk, including trauma with or without disseminated intravascular coagulation, were considered a contraindication for the drug. The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. Therefore, use of the drug in trauma patients suffering uncontrolled hemorrhage appears to be rational. METHODS: Seven massively bleeding, multitransfused (median, 40 units [range, 25-49 units] of packed cells), coagulopathic trauma patients were treated with rFVIIa (median, 120 microg/kg [range, 120-212 microg/kg]) after failure of conventional measures to achieve hemostasis. RESULTS: Administration of rFVIIa resulted in cessation of the diffuse bleed, with significant decrease of blood requirements to 2 units (range, 1-2 units) of packed cells (p < 0.05); shortening of prothrombin time and activated partial thromboplastin time from 24 seconds (range, 20-31.8 seconds) to 10.1 seconds (range, 8-12 seconds) (p < 0.005) and 79 seconds (range, 46-110 seconds) to 41 seconds (range, 28-46 seconds) (p < 0.05), respectively; and an increase of FVII level from 0.7 IU/mL (range, 0.7-0.92 IU/mL) to 23.7 IU/mL (range, 18-44 IU/mL) (p < 0.05). Three of the seven patients died of reasons other than bleeding or thromboembolism. CONCLUSION: The results of this report suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure, in addition to surgical hemostatic techniques, and provides the motivation for controlled animal and clinical trials.

Adolescent↗
PubMed2001

The inhibitory effects of colchicine on cell proliferation and mineralisation in culture.

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (3H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth.

Animals↗
PubMed2000

Cellular actin is affected by interaction with Candida albicans.

Attachment of Candida albicans, an important opportunistic pathogen, to host tissues is an initial step in the development of the infection. The events occurring in the fungal and in the host cells after interaction are poorly understood. In this study we concentrated on the events occurring in the mammalian cells after the interaction with Candida, with emphasis on the cytoskeleton actin. Human cell line cells (HEp2) were exposed to C. albicans or C. albicans-secreted material (culture filtrate) (actin-rearranging Candida-secreted factor, arcsf). The HEp2 cells were examined for cellular changes using confocal laser microscopy (CLSM), transmission and scanning electron microscopy (TEM and SEM). The CLSM studies, using fluorescein isothiocyanate-labeled C. albicans and rhodamine phalloidin actin staining, revealed yeasts adhering to the HEp2 cells or internalized into the cells, with actin surrounding the fungi. Furthermore, actin rearrangement from filamentous network to actin aggregates was noticed. Interaction between the HEp2 cells and C. albicans could be demonstrated also by SEM and TEM after a 2-4-h exposure of the cells to the fungus. Yeasts and hyphae were found attaching to the surface and within the cells. CLSM studies revealed that exposure of HEp2 cells to arcsf was also followed by cellular actin rearrangement, reduced membrane ruffling and decreased cellular motility. The effect was dose- and time-dependent. All these data indicate that the interaction of Candida with HEp2 cells involves signaling events and affects the cellular actin.

Actins↗
PubMed2000

[Prolonged neuromuscular damage following corticosteroids and muscle relaxants].

Many patients mechanically ventilated for acute respiratory failure, are treated with medication that includes a combination of cortico-steroids and non-depolarizing neuromuscular-blocking agents (NNBa). A third of them can be expected to develop delayed neuromuscular damage, which may be severe and prolonged. We describe a 50-year-old man who suffered from acute myeloid leukemia and was ventilated due to pneumonia. He was treated with pancuronium and cortico-steroids, and during recovery suffered quadriparesis that lasted several months. Typically this damage is purely motor and is accompanied by absent tendon-reflexes, sometimes with elevated creatine-kinase. Muscle biopsy usually shows deletion and degeneration of thick myosin filaments. The phenomenon is related to the duration of NNBa treatment, and probably results from an adverse synergistic effect on muscle tissue of the cortico-steroids and cortico-steroid-like NNBa given the immobilized patient. Awareness of this adverse effect of steroids and pancuronium, the use of passive mobilization, shortening the use of NNBa and early rehabilitation would minimize disability due to this phenomenon.

Adrenal Cortex Hormones↗
PubMed2000

Acquired tracheoesophageal fistula in critically ill patients.

Acquired benign tracheoesophageal fistula (TEF) is an infrequent complication of prolonged intubation and tracheostomy. Not infrequently, it is associated with severe circumferential malacia of the trachea and a need for concomitant correction of both. Controversy exists as to whether this should be performed in a single-stage or a 2-stage procedure. Four patients with acquired TEF underwent operation in a tertiary referral medical center between 1995 and 1997. The operations were performed through either an anterior (3) or a lateral (1) neck approach. Three patients underwent closure of the fistula with tracheal resection and anastomosis in a single stage and are doing well. One patient with complete subglottic stenosis underwent closure of the TEF and was planned for tracheal reconstruction in a second stage. This patient died in the early postoperative period. The complications included aspiration of blood leading to pneumonia (2), spontaneously resolving pneumomediastinum (1), subcutaneous emphysema (2), and cardiac arrhythmia ( 1). Residual fistula, noted in 1 patient, was treated conservatively and resolved spontaneously within several weeks. We conclude that acquired TEF is amenable to repair through a cervical approach. A single-stage correction of the TEF with reconstruction of the trachea is suitable and successful in most patients. Several stages seem justified when concurrent laryngotracheal reconstruction is needed.

Critical Illness↗
PubMed2000

Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA--a manifestation of the basic disease or the treatment.

All-trans-retinoic acid (ATRA) is considered the recommended induction treatment for acute promyelocytic leukemia. In the pre-ATRA era pulmonary bleeding was a common cause of death in these patients, mostly due to disseminated intravascular coagulation which was further exacerbated by the administration of chemotherapy. Although ATRA syndrome, the most serious adverse effect of ATRA treatment, involves the lungs, pulmonary hemorrhage has only rarely been reported as a manifestation of ATRA syndrome. Here we describe 2 patients who developed diffuse alveolar hemorrhage during treatment with ATRA. The possible mechanisms of pulmonary bleeding in these cases are discussed.

Adult↗
PubMed2000

The effect of full protective gear on intubation performance by hospital medical personnel.

OBJECTIVE: To assess the influence of protective gear on intubation performance. DESIGN: Prospective, controlled measurement of duration and quality of intubations performed on mannequins by medical personnel with and without protective gear in a crossover design. PARTICIPANTS: Eight teams each comprising an anesthesiologist and a nurse. RESULTS: Intubation duration with and without chemical warfare gear was 69.2 +/- 7 and 47.3 +/- 6 seconds (mean +/- SEM), respectively (p < 0.05). Moreover, rating of intubation quality as "very good" by the anesthesiologists declined significantly from 62.5% without chemical warfare protective gear to 6.25% with the garment and mask. Tube fixation was the rate-limiting step when performed with protective gear (p < 0.05); it was assessed by 81% of the anesthesiologists as the critical step. A learning curve was not observed during the study. CONCLUSION: Protective gear causes a significant prolongation of intubation duration; however, endotracheal intubation can be performed effectively. Technical improvements are warranted for tube fixation because it is the critical step.

Adult↗
PubMed2000

Natural pathogens of laboratory animals and their effects on research.

The natural fungal pathogens of laboratory animals such as rabbits and guinea pigs are mainly dermatophyte species, most commonly Trichophyton mentagrophytes and also, less frequently Microsporum gypseum and M. canis. However, the incidences of infection and clinical disease are low in well-managed animal facilities. Young or immunocompromised rabbits are thought to be most susceptible. Dermatophytes infect the epidermis and adnexal structures, including hair follicles and shafts, usually on or around the head, and cause pruritus, patchy alopecia, erythema and crusting. Histopathological changes in the underlying skin occur and these changes could confound histological studies involving the skin. Yeast infections usually due to Candida spp. have been reported occasionally in laboratory animals. In this paper, the role of rodents in the evaluation of topical antifungal agents, dermatophytosis and two species of Candida, which are natural pathogens of laboratory animals, are discussed in relation to their effects on research. Pneumocystis carinii, an inhabitant of the respiratory tract of laboratory mice and rats, is a pathogen only under conditions of induced or inherent immunodeficiency. Infected mice and rats are likely to develop severe pneumocystosis following immunosuppression and will be rendered unsuitable for most experimental purposes.

Animals↗
PubMed1999

The pharmacokinetics of morphine and lidocaine in critically ill patients.

OBJECTIVE: To evaluate the pharmacokinetic parameters of morphine and lidocaine after a single intravenous dose in critically ill patients. DESIGN: Prospective, clinical study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS: Patients admitted to the ICU with severe systemic inflammatory response syndrome of various etiologies. INTERVENTIONS: A single intravenous dose of morphine (0.025 mg/kg) and lidocaine (1.5 mg/kg) were given separately 12-36 h after admission, and arterial blood samples for serum drug levels were taken. MEASUREMENTS AND RESULTS: Morphine pharmacokinetics were studied in 30 patients. The clearance (Cl) was found to be 5.7+/-2.3 ml/kg per min, volume of distribution of the central compartment (Vc) 0.16+/-0.12 l/kg and volume of distribution at steady state (Vss) 1.08+/-0.69 l/kg. These values are lower then those described previously for healthy volunteers (33.5+/-9 ml/kg per min, 1.01+/-0.31 l/kg, and 5.16+/-1.4 l/kg, respectively), and similar to those described in trauma and burned patients. Lidocaine pharmacokinetics were tested in 24 subjects. The Cl was 6.9+/-3.8 ml/kg per min, Vc 0.25+/-0.1 l/kg and Vss 0.78+/-0.26 l/kg. These values are not different from parameters published previously for healthy volunteers (10 ml/kg per min, 0.53 l/min and 1.32 l/min, respectively). No correlation was found between clinical variables and pharmacokinetic parameters of both drugs (ANOVA). CONCLUSIONS: Both morphine and lidocaine have a reduced volume of distribution in critically ill patients. The normal lidocaine clearance indicates preserved hepatic blood flow and suggests that other mechanisms are involved in the reduced morphine clearance. These findings may have application for the treatment of ICU patients.

Adult↗
PubMed1999

Application of transcranial doppler ultrasonography for the diagnosis of brain death.

OBJECTIVE: To determine the clinical validity of transcranial Doppler ultrasonographic (TCD) signs of total cerebral circulatory arrest for confirmation of brain death and to define the test protocol. DESIGN: Study of a diagnostic test. SETTING: General and neurosurgery intensive care units. PATIENTS: 137 patients in a coma (Glasgow Coma Score 3-5), caused by various pathological conditions, observed from January 1992 to July 1998. 84 patients met the clinical criteria of brain death; 43 patients out of 137 received sedative drug therapy and 31 of these developed brain death. RESULTS: Total cerebral circulatory arrest was demonstrated by TCD in 81 patients. All of them proved to be brain dead according to subsequent clinical examination In 29 of 31 patients who had received sedative drug therapy TCD examination showed total cerebral circulatory arrest 12-48 h before the formal confirmation of the diagnosis. In 1 out of 84 clinically brain dead patients a false negative result was obtained. In 2 of 84 cases, no clear signals from intracranial vessels were obtainable. Fifty-three patients who did not meet the clinical criteria for brain death showed no TCD signs of total cerebral circulatory arrest. The specificity of the TCD test for confirmation of brain death was 100 % and the sensitivity 96.5 %. CONCLUSIONS: In agreement with previously published data, we conclude that TCD ultrasonography is a highly specific and sensitive confirmatory test and should be included as an additional test in the protocol for the assessment of brain death.

Adolescent↗
PubMed1999

The pharmacokinetics of morphine and lidocaine in nine severe trauma patients.

STUDY OBJECTIVE: To study the pharmacokinetic parameters of morphine and lidocaine after a single intravenous (i.v.) bolus in severe trauma patients. DESIGN: Clinical case study. SETTING: Department of Anesthesiology and Intensive Care of a university hospital. PATIENTS: Nine patients, ages 24 to 91 years (mean 54.4 yrs), admitted to the hospital with severe trauma (Injury Severity Score > 20) were included in the study. INTERVENTIONS: After initial evaluation and stabilization, a single i.v. dose of morphine 0.025 mg/kg and lidocaine 1.5 mg/kg was given separately, and blood samples were drawn for each drug serum concentration. MEASUREMENTS AND MAIN RESULTS: Morphine pharmacokinetics was studied in eight patients, lidocaine pharmacokinetics in seven patients, and both drugs were studied in six patients. Morphine clearance 2.5 to 10 ml/kg/min (6 +/- 2.6, mean +/- SD) and volume of distribution 0.28 to 3.30 L/kg (1.4 +/- 1.0) were found to be lower than values described previously for healthy volunteers (33.5 +/- 9 ml/kg/min and 5.16 +/- 1.40 L/kg, respectively), and are similar to those described in trauma patients (5 +/- 2.9 ml/kg/min and 0.9 +/- 0.2 L/kg, respectively). In contrast, lidocaine clearance 4.5 to 9.4 ml/kg/min (6.7 +/- 1.7) and volume of distribution 0.39 to 1.20 L/kg (0.72 +/- 0.28) were similar to the value described in healthy volunteers (10 ml/kg/min and 1.32 L/kg, respectively). CONCLUSION: Changes in pharmacokinetics of drugs eliminated by the liver may occur in patients with severe trauma. The preserved lidocaine clearance indicates an almost normal hepatic blood flow and suggests that other mechanisms may be involved in the lower morphine clearance. The findings may have applications for the treatment of severe trauma patients and suggest that drug monitoring might be needed in some instances so as to avoid toxicity.

Adult↗
PubMed1999

Antifungal activity of amphotericin B-lipid admixtures in experimental systemic candidosis in naive mice.

We have shown previously that admixtures of amphotericin B (AMB) and Intralipid (AMB-IL) obtained by vigorous and prolonged agitation are stable and can be standardized. These preparations exhibited in-vitro activity against various Candida spp., and had significantly lower toxicity. The present study was undertaken to evaluate the activity of AMB-IL admixtures in vivo in comparison with the conventional formulation of AMB (Fungizone), using a murine model of experimental systemic candidosis. ICR female mice (4-6 weeks old) were injected iv with 5 x 10(4) Candida albicans CBS 562. The animals developed a lethal infection (100%) within 10 days. Systemic candidosis was demonstrated by the presence of fungal elements in kidneys and spleen tissue, and by enumeration of cfu of Candida in the tissue homogenates. AMB-IL or AMB was administered iv 48 h post-Candida inoculation for 5 consecutive days. Four experiments with 108 mice treated with AMB 5 x 0.4 mg/kg and followed up for 6 weeks, showed that the mean survival percentages at the end of the experiment were 0, 24.9 and 52.5% for the untreated group, conventional AMB-treated and AMB-IL-treated groups, respectively. The mean survival time (MST) was 7.4, 25 and 30 days for the untreated, conventional AMB-treated and AMB-IL-treated groups, respectively. Use of increased doses of AMB showed that conventional AMB at doses greater than 5 x 1 mg/kg caused immediate animal death. AMB-IL was used at doses of AMB up to 5 x 2 mg/kg. Experiments with 104 mice revealed that the mean survival percentage at the end of the experiment was 0, 34.5, 58.6 and 97% for the untreated, conventional AMB-treated (5 x 1 mg/kg), AMB-IL-1-treated (5 x 1 mg/kg) and AMB-IL-2-treated (5 x 2 mg/kg) groups, respectively. The MST was 7, 27.8, 34.8 and 41.4 days for the untreated, conventional AMB-treated, AMB-IL-1-treated and AMB-IL-2-treated groups, respectively. The results of this study reveal that AMB-IL is significantly more effective in treating systemic murine candidosis than conventional AMB.

Amphotericin B↗
PubMed1999

Elevated plasma atrial natriuretic peptide levels after occlusion of the thoracic aorta.

STUDY OBJECTIVE: The influence of occlusion of the thoracic aorta by an intraluminal balloon on plasma atrial natriuretic peptide (ANP) levels was evaluated in humans. METHODS: The changes in plasma ANP and plasma norepinephrine levels, and hemodynamic parameters were measured in 10 patients under general anesthesia undergoing regional chemotherapy treatment involving the 15-min inflation and subsequent deflation of an intraaortic balloon. RESULTS: The hemodynamic changes observed were similar to those seen during aortic clamping and declamping in patients undergoing vascular surgery. Plasma ANP levels (median+/-SD) measured 1 min after inflation (146+/-117 pg/mL) and 1 min after deflation (168+/-189 pg/mL) of the aortic balloon were significantly higher than baseline values (83+/-55 pg/mL), with a mean increase, respectively, of 92% and 97% (95% confidence intervals [CI], 50 to 147% and 53 to 152%). Plasma ANP levels were still elevated 30 min after deflation (121+/-94 pg/mL), a 56% increase (95% CI, 21 to 100%), although the hemodynamic parameters had already returned to their baseline levels. There was no evidence that the hemodynamic variables were associated with changes in plasma ANP levels (all p values > 0.30). In addition, there was no evidence of an association between plasma ANP and plasma norepinephrine levels at any of the four individual sampling points (p > 0.17). Thirty minutes after deflation, however, norepinephrine levels were higher than baseline values. CONCLUSIONS: The changes in plasma ANP levels after aortic occlusion and reinstitution of blood flow may be dependent on parameters other than atrial stretch and pressure.

Abdominal Neoplasms↗
PubMed1999

Experimental candidosis. Pathogenesis, prevention, therapy.

This article highlights some aspects of candidosis which were explored in different models and which yielded relevant information with respect to pathogenesis as well as possibilities of prevention and treatment of candidosis.

Amphotericin B↗