Biomedical subjects
E Segal
Publications and source records attributed to E Segal.
Adhesion of Candida albicans mutant strains to host tissue.
Adhesion of Candida albicans to host cells is believed to represent a fungal virulence factor and a significant step in the development of candidiasis. As C. albicans strains may differ in their in vitro adhesion ability we initiated a study to investigate whether mutant strains differ in this respect from their parent wild-type. We assessed the in vitro adhesion of C. albicans CBS562 and two mutants obtained by mutagenesis with N'-nitrosoguanidine: a histidine auxotroph, SAG5, derived from CBS562, and a respiratory-deficient strain (a petite mutant), SAR1, derived from SAG5. The adhesion was tested in vitro using two target cell systems: (1) exfoliated human buccal epithelial cells (BEC); and (2) human keratinocyte tissue line cells (HaCaT cells). Adhesion to BEC was evaluated microscopically and that to HaCaT cells by a direct ELISA technique. The results indicated a 54% reduction in adhesion to BEC for SAG5 and 30% for SAR1 as compared to the wild-type, and a 25% reduction in adhesion to HaCaT cells for SAG5 and 20% for SAR1. To verify whether the prototrophy restores the adhesion ability, we complemented the his-negative auxotroph by transforming the strain with the HIS4 gene. Then we assayed the adhesion to BEC of the complemented his-negative mutant in comparison to that of the wild-type, the his-negative mutant (SAG5) and the plasmid-cured transformant. The adhesion values of the complemented his-negative strain were similar to those of the wild-type, whereas the values of the plasmid-cured strain were similar to those of SAG5.
[Massive pulmonary embolism--summary of experiences with 13 patients].
Pulmonary embolism is a common event in hospitalized patients. In some cases it presents with hemodynamic collapse, indicating massive obliteration of the pulmonary vasculature and has a very grim prognosis; 2/3 of such patients die within 2 hours of onset of symptoms. We describe our experience in 13 patients with massive pulmonary embolism. An aggressive diagnostic and therapeutic approach, utilizing sophisticated imaging techniques, thrombolytic therapy and surgery, led to the survival of 8 of the patients. Our experience supports an aggressive approach in these seriously ill patients.
[Closed intramedullary nailing of forearm fractures in young patients].
Forearm bone fractures are commonly the result of falling on the outstretched hand or of direct injury. The preferred treatment is debated. The possible modalities are: application of a cast, often necessitating repeated manipulations; open reposition and fixation by plates and screws; or closed manipulation and closed intramedullary nailing. We present our favorable results in treating these fractures in young patients by closed intramedullary nailing, and compare them with the unfavorable results of this method in mature adults.
Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term follow-up.
Corticosteroids continue to be used by many physicians to treat infants with bronchiolitis. The aim of this study was to examine the short-term and long-term efficacy of oral corticosteroid therapy when added to beta2-agonists in infants with mild to moderate bronchiolitis (defined as the first episode of wheezing associated with low grade fever, rhinitis, tachypnea, and increased respiratory effort in a previously healthy infant during the winter months). Infants with mild to moderate bronchiolitis, were randomly assigned to receive either oral prednisone (2 mg/kg/day) or placebo for 3 days. All patients received nebulized albuterol q.i.d. during this period. Upon admission and after 3 days of therapy, a clinical score was assigned based on respiratory rate, use of accessory muscle, and the presence of wheeze. Oxygen saturation (SaO2) was also measured. On day 7, we inquired as to the well-being of each child. Two years later, the development of chronic respiratory symptoms was assessed. Thirty-eight infants were enrolled in the study; 20 received prednisone and 18 received placebo. Both groups were similar in terms of age, duration of illness prior to enrollment, pretrial medication use, clinical severity of bronchiolitis, history of atopy, and family history of atopy. After 3 and 7 days of treatment, both groups showed similar clinical improvement and there were no statistically significant differences between the two groups in the clinical score or in the SaO2. No major side effects were observed. Two years later, 32% of the infants continued to suffer from chronic respiratory symptoms, with a similar prevalence in both groups. We conclude that a 3-day course of oral corticosteroids is of no benefit to infants with mild to moderate bronchiolitis who are also treated with an inhaled beta2-agonist.
Evaluation of simplified Frykman and AO classifications of fractures of the distal radius. Assessment of interobserver and intraobserver agreement.
In order to evaluate interobserver and intraobserver agreement of the Frykman and AO classifications and their variations between assessors with different levels of experience, three hand specialists, a fellow and two senior residents classified radiographs of 200 fractures of the distal radius in anteroposterior and lateral views. Reproducibility was assessed by the use of the proportion of agreement and kappa coefficient between pairs of observers. The Frykman classification showed moderate interobserver reproducibility (kappa = 0.43) and good intraobserver reproducibility (kappa = 0.61). The experience of the reviewers did not significantly affect either of these. The AO system showed regular interobserver reproducibility (kappa = 0.37) and moderate intraobserver reproducibility (kappa = 0.57). The younger group obtained higher intraobserver agreement than the senior. Possible causes for the low reproducibility of both classifications are discussed together with a review of the literature. We do not recommend the Frykman or AO classifications for clinical application because of their questionable reproducibility.
Isolation of a petite mutant from a histidine auxotroph of Candida albicans and its characterization.
Respiration-deficient (petite) mutations have been induced in various yeasts, which are categorized as petite-positive. Candida albicans was classified among the petite-negative yeasts. Since then, a few reports have appeared, describing the isolation of petite mutants in C. albicans. We report in the present study on the isolation of a petite mutant of C. albicans-SAR1. This mutant was isolated from a histidine auxotroph of C. albicans after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine, thus our petite mutant carries a double mutation. SAR1 was characterized morphologically, biochemically and ultrastructurally. The results revealed differences from the wild type in respect to morphological, physiological and biochemical characteristics. Electron microscopy showed that the cells of the petite mutant contain only very few mitochondria that looked 'thread like' without any cristae. The significance of the mutation in the virulence of the mutant vs. that of the wild-type is being assessed.
[Nontuberculous mycobacteria in patients with cystic fibrosis].
The prevalence of nontuberculous mycobacteria (NTM) isolated from the lower airways of adult cystic fibrosis (CF) patients appears to be increasing. Different centers of USA, England, Sweden and Ireland have reported a prevalence ranging from 1.5 to 19.5%. The aim of the present study was to investigate the presence of NTM in patients assisted at these centers. A total of 92 sputum specimens and/or gastric contents from 40 CF patients were studied. Ages of patients ranged from 4 months to 25 years. Samples were obtained during acute exacerbation or in routine check-up. Mycobacterium avium-intracellulare complex strains were isolated from six patients with moderate or severe clinical manifestations. Five of these patients were considered as being colonized by NTM. Active mycobacterial disease was diagnosed in one patient and he underwent treatment. The index of bacterial contamination of cultures was very high early along the study (57%), decreasing to 2.8% later due to a change in the methodology used in the processing of samples. It was concluded that the presence of NTM is relatively frequent in patients with CF, even in children with moderate or severe compromise, a fact which strongly suggests that NTM should be systematically searched for considering the possibility that the patients might develop active disease.
[Airway management of the multiple trauma patient].
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Chronic massive knee effusion in familial Mediterranean fever.
OBJECTIVE: To document the occurrence of chronic massive knee effusions in patients with familial Mediterranean fever (FMF). PATIENTS: Three cases of chronic massive knee effusion of young FMF patients requiring open synovectomy are presented. RESULTS: Open synovectomy necessitated protracted rehabilitation, eventually with good results. CONCLUSIONS: FMF should be considered in the differential diagnosis of chronic massive knee effusion. Early diagnosis and daily colchicine treatment generally result in a good clinical outcome and may eliminate the need for open synovectomy in favor of arthroscopic surgery.
Liposomes containing Candida albicans ribosomes as a prophylactic vaccine against disseminated candidiasis in mice.
This study describes the development of prophylactic anti-Candida vaccine which combines the advantages of Candida albicans ribosomes as antigen(s) and of liposomes as carrier/adjuvant with minimal side-effects, which could be suitable for human use. The liposomal vaccine was composed of C. albicans ribosomes and the lipids dimyristoyl phosphatidyl choline (DMPC) and dimyristoyl phosphatidyl glycerol (DMPG) (9:1 molar ratio). Some of the vaccines contained Lipid-A (LA) as an additional adjuvant. The vaccine was prepared by two methods: (I) dehydration by lyophylization of small liposomes in the presence of the Candida ribosomes (DRV method); (II) colyophylization of DMPC/DMPG (9:1 mole ratio) in tertiary butanol with aqueous dispersion of Candida ribosomes. In both cases a dry powder was obtained which was rehydrated to form large multilamellar vesicles. The efficacy of the vaccines in mice was tested by their protectivity against a challenge with C. albicans, as assessed by survival rate, induction of cell mediated immunity (measured by delayed type hypersensitivity-DTH) and anti-Candida antibody titer. Unimmunized mice and mice vaccinated by ribosomes supplemented with incomplete Freund's adjuvant (IFA) were used as controls. The results indicated that the liposomal vaccines were effective at least as the IFA-based vaccine. The study indicates the feasibility of developing an efficacious anti-Candida vaccine for human use.
The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures.
The use of Intralipid as a dilution medium for Fungizone, previously proposed by several groups to reduce the toxicity of amphotericin B, is limited by the instability of amphotericin B-lipid admixtures. We have shown that Fungizone-lipid admixtures with three different lipid emulsions can be stabilized by vigorous agitation. Unlike in preparations made by gentle shaking, in stable emulsions made by agitation for 18 h, most of the amphotericin B remains associated with the lipid phase for at least 1 month at 4 degrees C. The MICs of all the admixtures against various Candida spp. were similar to that of Fungizone and did not change following storage for at least 2 weeks at 4 degrees C. Furthermore, the toxicity of the admixtures, as evaluated by their haemolytic activity and amphotericin B-induced K+-leakage from human red blood cells, was much lower than that of Fungizone. Hence, amphotericin B-containing lipid emulsions made by extended agitation may be advantageous in clinical practice as they are efficient, stable, non-toxic and can be easily produced at low cost from commercially available ingredients approved for clinical use.
Spectrum of CFTR mutations in Argentine cystic fibrosis patients.
The identification of different mutations which cause cystic fibrosis (CF) in Argentine patients has been performed. Initially, 10 of the most commonly mutated loci in 228 independent chromosomes were analyzed. Each allele was detected by PCR amplification of DNA samples either directly on polyacrylamide gels, by restriction enzyme digestion and agarose gels electrophoresis, or by hybridization with allele specific oligonucleotides. The delta F508 mutation was found in 57% of the alleles. The frequencies of the other CF mutations were as follows: G542X 3.9%, W1282X 3.1%, N1303K 1.7%, 1717 1-G-->A 0.9%, R553X 0.4%, R1162X 0.4%, whereas G551D, delta I507 and S549N were not found. This direct mutation analysis enabled the detection of 155/228 CF alleles (67%). Of the remaining 73 unidentified CF alleles, 22 were investigated for the 27 exons by DGGE and 9 rare mutations were identified. The incidence of the main CF mutations analyzed was similar to that of the South European population and markedly different from other Latin American countries. The mutation data presented here may be useful for designing DNA testing strategies for CF in Argentina.
[Hemato-oncology patients in acute respiratory failure in the ICU].
Hemato-oncology patients needing mechanical ventilation for acute respiratory failure (ARF) have an extremely poor prognosis, with a mortality of more than 90%. Over an 18 month-period 17 such patients were admitted to our ICU. Diagnoses included leukemia (11 cases), lymphoma (1), and status post bone marrow transplantation for leukemia, lymphoma or breast cancer (5). Of 8 whose ARF was associated with septic complications due to neutropenia following chemotherapy, 6 survived. Of 9 who developed ARF due to toxic damage to vital organs following high-dose chemotherapy, 2 survived. Those who develop ARF during chemotherapy are expected to have an increase in granulocyte count within days, and have a surprisingly good prognosis. They should be admitted to the ICU and treated aggressively. Those who develop sepsis due their primary disease and whose general condition contraindicates chemotherapy, have an extremely grave prognosis and admission to the ICU may not be warranted.
[Transport of critically ill patients].
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[Dopamine and the kidney--renal sparing effect: fact or fiction?].
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Pressure support ventilation.
The field of ventilatory support has changed dramatically with the introduction of improvements in technology and new ventilatory modes. The most recent ventilators are characterized by microprocessor technology, making the interaction between patient and ventilator more sophisticated than ever before. This technology has enabled the development of pressure support ventilation, which has gained extensive popularity during the past 10 years. Pressure support ventilation is different from controlled mechanical ventilation or intermittent mandatory ventilation; pressure support ventilation is characterized by a unique combination of simultaneous spontaneous and mechanical breathing, so that the ventilatory and flow rates and tidal volume depend on the patient's breathing pattern and the set level of pressure support. Pressure support ventilation can be used as a stand-alone ventilatory support mode and alternative to volume-controlled ventilation, and it can be used in weaning patients from mechanical ventilation.
Identification of three novel mutations in the cystic fibrosis transmembrane conductance regulator gene in Argentinian CF patients.
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