Search PubMed⌕ Search

Biomedical subjects

A Oppenheim

Publications and source records attributed to A Oppenheim.

At least 37 records · Page 2Linked to original sources
PubMed1998

Helium versus oxygen for tracheal gas insufflation during mechanical ventilation.

OBJECTIVE: To evaluate and compare the effect of tracheal gas insufflation using two gases with different physical properties, helium and oxygen, as an adjunct to conventional mechanical ventilation in patients with respiratory failure. DESIGN: Prospective, intervention study. SETTING: General intensive care unit in a tertiary university medical center. PATIENTS: Seven sedated and paralyzed patients with respiratory failure of various etiologies. All patients were ventilated in the volume-control mode (tidal volume 5 to 7 mL/kg). Inclusion criteria were PaCO2 of > or =50 torr (> or =6.7 kPa), together with peak inspiratory pressure of > or =35 cm H2O and respiratory rate of > or =14 breaths/min. INTERVENTIONS: All patients were intubated with an endotracheal tube that had an additional lumen opening at its distal end, through which tracheal gas insufflation was administered. The tracheal gas insufflation was applied continuously throughout the respiratory cycle at three flow rates (2, 4, and 6 L/min) with two gases, oxygen and helium, while the ventilatory settings were maintained constant. MEASUREMENTS AND MAIN RESULTS: In addition to airway pressures and arterial blood gases, the relative efficacy of tracheal gas insufflation with each gas was estimated using a "coefficient of efficiency" (which we defined as the change in PaCO2/peak inspiratory pressure) compared with baseline measurements. Tracheal gas insufflation with both gases decreased PaCO2 significantly (p < .05) at all flow rates. This effect was accompanied by an increase in airway pressure with both gases (oxygen and helium). However, at flow rates of 6 L/min, tracheal gas insufflation with helium resulted in lower peak inspiratory pressure than with oxygen. Tracheal gas insufflation with helium was more effective (as estimated by the coefficient of efficiency) than with oxygen at all flow rates (p < .05). CONCLUSION: In volume-controlled, mechanically ventilated patients with respiratory failure, tracheal gas insufflation with helium might be suggested as an alternative to oxygen.

Acute Disease↗
PubMed1998

Tension pneumoperitoneum after blast injury: dramatic improvement in ventilatory and hemodynamic parameters after surgical decompression.

Tension pneumoperitoneum is a known although rare complication of barotrauma, which can accompany blast injury. We report two patients who suffered from severe pulmonary blast injury, accompanied by tension pneumoperitoneum, and who were severely hypoxemic, hypercarbic, and in shock. After surgical decompression of their pneumoperitoneum, respiratory and hemodynamic functions improved dramatically. Several mechanisms to explain this improvement are suggested. In such cases the release of the tension pneumoperitoneum is mandatory, and laparotomy with delayed closure can be contemplated.

Adult↗
PubMed1997

Self-assembly and protein-protein interactions between the SV40 capsid proteins produced in insect cells.

Soluble SV40 capsid proteins were obtained by expression of the three late genes, VP1, VP2, and VP3, in Sf9 cells using baculovirus expression vectors. Coproduction of the capsid proteins VP1, VP2, and VP3 was achieved by infecting Sf9 cells with the three recombinant baculovirus species at equal multiplicities. All three proteins were found to be localized in the nuclear fraction. Electron microscopy of nuclear extracts of the infected cells showed an abundance of SV40-like capsid structures and heterogeneous aggregates of variable size, mostly 20-45 nm. Under the same staining conditions wild-type SV40 virions are 45 nm. The capsid-like particles sedimented in glycerol gradients similarly to authentic wild-type SV40 virions. Pentamers of the major capsid protein VP1 were also seen. Protein analysis on sucrose gradients demonstrated that the capsid-like particles can be disrupted by treatment with the reducing agent dithiothreitol and the calcium chelator EGTA. The capsid-like particles were found to be significantly less stable than SV40 virions and were partially stabilized by calcium ions. Understanding the complex interactions between the capsid proteins is important for the development of an efficient in vitro packaging system for SV40 virions and pseudovirions.

Animals↗
PubMed1997

In vitro assembly of SV40 virions and pseudovirions: vector development for gene therapy.

SV40 is an attractive potential vector with high-efficiency gene transfer into a wide variety of human tissues, including the bone marrow, a critical target organ for the cure of many diseases. In the present study, the three SV40 capsid proteins, VP1, VP2, and VP3, were produced in Spodoptera frugiperda (Sf9) insect cells. Their co-production led to spontaneous assembly of SV40-like particles. Nuclear extracts containing the three proteins were allowed to interact with purified SV40 DNA, or with plasmid DNA produced and purified from Escherichia coli. The experiments demonstrated a physical association between the DNA and capsid proteins, protection from DNase I digestion, and the formation of infectious particles. The results indicate that intact, supercoiled DNA is being packaged and transmitted into the target cells. The transmitted DNA is biologically functional in gene expression and replication. The process, which utilizes naked DNA, is not dependent on the SV40 packaging signal ses. The procedure allows packaging of plasmids significantly larger than SV40 and permits the inclusion of potent regulatory signals, such as beta-globin locus control region (LCR) elements. These studies are the first step in the development of purified, in vitro-constructed pseudovirions for experimental and medical use.

Animals↗
PubMed1997

Genetic analysis of beta-thalassemia intermedia in Israel: diversity of mechanisms and unpredictability of phenotype.

Molecular analysis was performed on 95 Israeli patients with thalassemia intermedia, representing 60 families of Arab (Moslem and Christian), Jewish, Druze, and Samaritan origin. There was a wide range of phenotypic severity, with baseline hemoglobin levels ranging from 5.5 to 10.7. Eighteen thalassemia mutations were found (29 genotypes), which were subdivided into groups, according to the severity of mutations. A consistently mild phenotype (10 families) was caused by compound heterozygosity for a silent mutation, such as -101 C-T or by coexistence of triplicated alpha-globin genes with thalassemia trait. In 39 thalassemia intermedia families, the genotype which was found was one which led to severe thalassemia intermedia, or, in other families, was associated with thalassemia major. Elevated hemoglobin F ameliorated the disease in some patients with a severe genotype. We did not find a beneficial effect of concurrent alpha-thalassemia in any of the families studied. In 11 families, only one beta-thalassemia allele was identified. One was a dominant thalassemia intermedia allele. Three additional families with heterozygous beta-thalassemia had excess alpha-globin genes (5 or 6 total). In 7 of these heterozygotes, no explanation was found for the thalassemia intermedia phenotype. Our results suggest a substantial influence of as yet unknown genetic modifiers. These findings have important implications for prenatal diagnosis and for the genetic counseling of families with thalassemia intermedia.

Alleles↗
PubMed1997

A novel mechanism generating short deletion/insertions following slippage is suggested by a mutation in the human alpha2-globin gene.

A novel mechanism generating short deletion/insertions is described based on a mutation in the human alpha2-globin gene. A deletion of 9 bp (codons 39-41) is replaced by an eight nucleotide insertion, duplicating the adjacent downstream sequence. We propose that the mutation arose by slipped strand mispairing (SSM), creating a single-stranded loop, followed by DNA elongation, strand breathing and the formation of a mismatch bubble. An extensive literature search has revealed six additional deletion/insertion mutations in humans in which the inserted nucleotides come from the same DNA strand. Our model explains all six mutations, suggesting that rearrangement of a mismatch loop or bubble during DNA replication may be not uncommon.

Adolescent↗
PubMed1997

Positive end-expiratory pressure increases pulmonary venous vascular resistance in patients after coronary artery surgery.

OBJECTIVE: To investigate the effect of positive and-expiratory pressure (PEEP) on the longitudinal distribution of pulmonary vascular resistance in patients immediately after coronary artery bypass grafting. DESIGN: Prospective, intervention study. SETTING: Postcardiac surgery intensive care unit in a teaching institution. PATIENTS: Twenty patients after elective coronary artery bypass grafting. INTERVENTION: The effect of PEEP on pulmonary circulation, at four different levels (0, 5, 10, and 15 cm H2O), was analyzed in 20 patients. MEASUREMENTS AND MAIN RESULTS: Mean pulmonary arterial pressure, left atrial pressure, pulmonary artery occlusion pressure, and pulmonary capillary pressure were measured at each PEEP level. A model consisting of two resistances in series was used to analyze the effect of PEEP on the pulmonary circulation. The pulmonary vascular resistance for each area (arterial and venous) of the circulation was calculated. Pulmonary vascular resistance increased from 216 +/- 70 dyne.sec/cm5 at a PEEP of 0 cm H2O to 308 +/- 125 dyne.sec/cm5 at a PEEP of 15 cm H2O (p < .001). This increase, however, resulted solely from an increase in the resistance of the venous part of the pulmonary circulation from 66 +/- 29 to 134 +/- 69 dyne.sec/cm5 (p < .001), without any change in pulmonary arterial resistance. CONCLUSIONS: PEEP increases pulmonary vascular resistance solely by increasing pulmonary venous resistance. When applying PEEP, changes in pulmonary vascular resistance may impede the resorption of pulmonary edema fluid.

Aged↗
PubMed1996

The simian virus 40 packaging signal ses is composed of redundant DNA elements which are partly interchangeable.

Using the experimental system of simian virus 40 (SV40) pseudovirions we have previously shown that SV40 requires a specific DNA element for packaging, ses, which was mapped to the SV40 regulatory region. ses was previously found to play a role in facilitating the nucleosomal rearrangement required for chromatin condensation and viral packaging. Here, the fine structure of ses was investigated by genetic studies. Analyses of ses+ revertants indicated that in order to function, ses must be present in close proximity to the origin of replication (ori), supporting a role in the regulation of the viral life cycle. Fine dissection of ses was performed using a series of plasmids carrying mutations and deletions in this region. The results suggest that multiple DNA elements participate in the SV40 packaging process, including the GC-boxes and elements derived from the enhancer. The elements are redundant, and they can function in various combinations. Packaging efficiency correlated with the number of GC-boxes, known to bind Sp1. In addition, AP-2 binding elements appeared to more important than others. These findings were supported by experiments which showed that packaging was significantly enhanced by adding AP-2 binding sites to plasmids with large deletions and lacking those sites. The results imply that binding of Sp1 and/or AP-2 may participate in the packaging process.

Animals↗
PubMed1996

[Epidural analgesia for postoperative pain in infants and children].

Until recently it was thought that children do not suffer as much from postoperative pain as adults. Coupled with the fear of administering systemic opiates to young children, this meant that babies were often left "to cry it out." Lately it has been acknowledged that children and even babies not only feel pain, but similar to adults, suffer from the physiologic consequences of the untreated stress response. It has also been shown that preventing this response improves the postoperative period in babies after undergoing cardiac surgery. Regional analgesia is commonly used to provide postoperative pain control in adults and children. Following minor lower abdominal surgery, pain relief is often provided by caudal analgesia or specific nerve blocks. Epidural and spinal anesthesia are also gaining popularity for young children and even babies. We describe 3 cases of continuous epidural analgesia in babies, and review other methods for postoperative pain relief. These cases are representative of the many which we have treated over the past 2 years. We use epidural analgesia in children who undergo major thoracic, abdominal, pelvic and major lower limb surgery, and are expected to suffer significant postoperative pain for more than 24 hours. We have not encountered any major complications or inadvertent dural punctures. We judiciously monitor these children, especially their respiratory function, as long as they receive epidural narcotics.

Adult↗
PubMed1996

Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease.

Chitin, the second most abundant polysaccharide on earth, is degraded by chitinases and chitobiases. The structure of Serratia marcescens chitobiase has been refined at 1.9 A resolution. The mature protein is folded into four domains and its active site is situated at the C-terminal end of the central (beta alpha)8-barrel. Based on the structure of the complex with the substrate disaccharide chitobiose, we propose an acid-base reaction mechanism, in which only one protein carboxylate acts as catalytic acid, while the nucleophile is the polar acetamido group of the sugar in a substrate-assisted reaction. The structural data lead to the hypothesis that the reaction proceeds with retention of anomeric configuration. The structure allows us to model the catalytic domain of the homologous hexosaminidases to give a structural rationale to pathogenic mutations that underlie Tay-Sachs and Sandhoff disease.

Acetylglucosaminidase↗
PubMed1996

Second transplantation using allogeneic peripheral blood stem cells in a beta-thalassaemia major patient featuring stable mixed chimaerism.

Allogeneic bone marrow transplantation (BMT) for beta-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.

Bone Marrow Transplantation↗