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Biomedical subjects

M Gilbert

Publications and source records attributed to M Gilbert.

At least 109 records · Page 6Linked to original sources

Extracorporeal membrane oxygenation (ECMO) as lung or heart assist.

Extracorporeal membrane oxygenation (ECMO) may serve as extracorporeal lung assist (ECLA) in patients with acute respiratory failure (ARF) or as extracorporeal heart assist (ECHA) in patients with low output syndrome (LOS) after open heart surgery. From 1988 to 1992 seven patients underwent ECMO in our hospital; four suffered from ARF and three from LOS. Various bypass techniques were employed. Two ARF patients, aged 58 and 18 years, had veno-venous bypass; in the latter, ECMO was reinstituted as a veno-arterial bypass one week after weaning. In a three-year-old boy, the ECMO outflow tubing was primarily connected to the pulmonary artery, and shortly afterwards relocated to the common carotid artery. In a 31-year-old man with ARF, and three LOS patients, a 56-year-old woman, and two men aged 68 and 70 years, ECMO was veno-arterial with direct access to the ascending aorta. A heparin-coated system was used, and all but one patient, who was treated with warfarin, received a daily low dose of heparin, which was withdrawn after from one to nine days. Six patients were weaned off ECMO after 4.5 to 21 days. Three ARF patients recovered completely; the child died. In one LOS patient, ECMO was withdrawn due to a poor general condition. Two others were weaned off ECMO and the intra-aortic balloon pump, and the inotropic support was significantly reduced, but both died of multiple system organ failure. Although no firm conclusions can be drawn from these few case reports, the heparin-coated system used as ECLA appears promising, whereas ECHA seems to imply a poor prognosis in patients who are not candidates for cardiac transplantation.

Acute Disease↗

Initial experience with 1.5-mm2 high impedance, steroid-eluting pacing electrodes.

UNLABELLED: In this human study, 21 atrial and 62 ventricular 1.5-mm2 unipolar steroid-eluting pacing electrodes were implanted in 64 patients. Pacing thresholds, lead impedance, and sensing measurements were measured via pacemaker telemetry within 24 hours postimplant, and at 1, 2, 3, 4, 6, 12, 24, and 52 weeks. Acute pacing impedances measured via a pacing systems analyzer were 1,039 +/- 292 (atrial) and 1,268 +/- 313 ohms (ventricular). A 10%-15% decline in the mean telemetered atrial and ventricular pacing impedances was observed at 1 week, but thereafter remained stable. Acute pacing thresholds at 0.5 ms were 0.5 +/- 0.3 V (atrial) and 0.4 +/- 0.1 V (ventricular). Filtered P and R wave amplitudes were 3.7 +/- 2.3 mV and 14.9 +/- 5.9 mV, respectively. In 21 patients, no complications related to the atrial electrode were observed. Of 62 patients with ventricular electrodes, 4 patients (6%) experienced complications and required surgical intervention. On these, causative factors included micro-dislodgment (1 patient), and perforation (1 patient). Sudden unexplained exit block occurred late (> 6 weeks) in two patients. In the remainder of patients, pacing thresholds and sensed electrogram amplitudes remained stable throughout the 52-week follow-up period. CONCLUSIONS: The present study validates that smaller surface (i.e., 1.5 mm2) steroid-eluting electrode designs offer excellent pacing and sensing performance with significantly higher pacing impedances. Although questions remain as to the cause of late exit block in two patients in this series, this relatively small surface electrode design offers promise toward achieving greater pacing efficiency and a theoretical 13%-16% (minimum) enhancement in permanent pacemaker longevity.

Administration, Topical↗

Bacterial secretion of the Fab fragment of a mouse monoclonal IgM that reacts with IgG variable regions.

In this report, we describe the expression system that enabled us to produce in Escherichia coli the Fab fragment of a mouse IgM that has previously been shown to inhibit the binding of IgG to autoantigens by interacting with their variable regions. In our system, both light chain and heavy chain fragments were put under the control of the malE promoter. The light chain was fused to the MalE signal sequence, while the heavy chain variable and first constant region were fused to the alkaline phosphatase signal sequence. In this system, after induction of the promoter with maltose, the Fab fragment could be detected in a periplasmic extract of the bacteria by Western blotting and also by ELISA. This Fab fragment was purified on a goat anti-mouse immunoglobulin immunoadsorbent and biotinylated. The Fab fragment produced by E.coli reacted with the trinitrophenyl (TNP) hapten and F(ab')2 fragments of mouse IgG and these reactivities could be specifically inhibited by the corresponding soluble antigens. The dissociation constants of this Fab were 1.65 x 10(-6) M for TNP and 5 x 10(-6) M for IgG F(ab')2 fragments, indicating that the affinity of the Fab fragment compared with that of the whole IgM molecule was similar for TNP but was lower for IgG F(ab')2 fragments.

Animals↗

Nimodipine: a drug therapy for treatment of vasospasm.

Cerebral vasospasm presents a challenge for the nursing staff. To date, no effective prevention methods have been identified. The key to decreasing the mortality rates is in discovering a method of preventing or reversing the arterial narrowing caused by vasospasm. The nurse needs to be aware of the theories of vasospasm and the rationale for treatment. Neurologic assessment skills are important for the nurse to detect minimal changes that may indicate vasospasm. Nurses who are informed will be able to provide optimal care to patients with cerebral vasospasm and provide the necessary support for family members. Drug therapy continues to be the first-line defense in treating vasospasm. Nimodipine is a very promising drug with demonstrated effectiveness to reduce the neurologic deficits caused by vasospasm. Further research on the treatment of vasospasm following SAH is currently in progress.

Humans↗

In vivo effects of glucose and insulin on secretion and gene expression of glucagon in rats.

We investigated the effects of insulin and glucose on the control of secretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemia plus hyperinsulinemia; EG-HI rats), and 2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of plasma insulin and glucose concentrations by about 7 and 5 times, respectively, resulted in a decline in glucagon levels, which fell significantly within 6 h and remained low thereafter, whereas these levels were unchanged in EG-HI rats. Glucagon messenger RNA levels and pancreatic glucagon content were not significantly affected in either HG-HI or EG-HI rats. After cessation of infusions, hypoglycemia occurred in both group of rats. In HG-HI rats, hypoglycemia lasted for about 36 h without any surge in the plasma glucagon level, whereas in EG-HI rats it was transient (approximately 1 h) and stimulated glucagon secretion. In both groups the pancreatic alpha-cell was unresponsive to arginine during the postinfusion period. In conclusion, although a role of intraislet insulin cannot be excluded, glucagon gene expression is insensitive to changes in plasma glucose and insulin concentrations. In contrast, hyperglycemia/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the alpha-cell responsiveness to hypoglycemia.

Animals↗

Production and secretion of proteins by streptomycetes.

Streptomycetes produce a large number of extracellular enzymes as part of their saprophytic mode of life. Their ability to synthesize enzymes as products of their primary metabolism could lead to the production of many proteins of industrial importance. The development of high-yielding expression systems for both homologous and heterologous gene products is of considerable interest. In this article, we review the current knowledge on the various factors that affect the production and secretion of proteins by streptomycetes and try to evaluate the suitability of these bacteria for the large-scale production of proteins of industrial importance.

Amino Acid Sequence↗

Coordinated care for the SCI patient.

The delivery of quality patient care in a timely, cost-effective manner is of utmost importance in health care settings. In an attempt to promote continuity and coordination of care, appropriate utilization of resources, and increased patient and health care provider satisfaction, a coordinated care system of patient care delivery was implemented for the spinal cord injured patient. Coordinated care is a multi-disciplinary approach that focuses on achieving patient outcomes within effective time frames which have been established by all members of the health care team involved in the treatment of the SCI patient. Integral to the concept of coordinated care is the utilization of a critical path and variance tracking and analysis. A critical path is a multidisciplinary plan which identifies the time frame in which key events and patient outcomes should occur during an episode of care in order to achieve an optimal use of resources and length of stay. Variance tracking is the comparison of the actual care delivered with the expected plan and the identification of reasons why the care differed.

Case Management↗

Incidence of hepatitis C in patients requiring orthopaedic surgery.

We tested prospectively for hepatitis C virus (HCV) in one orthopaedic surgeon's operative practice for one year. Of 425 consecutive patients, 19 (4.5%) were positive for HCV infection using a second-generation screening assay. The highest correlation with a positive test was the presence of tattoos and the second highest was intravenous drug abuse, but only after a second interview, since most patients did not report this risk on the initial questionnaire. Based on the criteria of the US Public Health Services algorithm, nine (47%) of the patients with a positive initial screening test or 2.2% of the 425 patients, had hepatitis C (both anti-HCV-positive and elevated alanine aminotransferase). In this group of nine, the presence of tattoos had the highest and intravenous drug abuse the second highest correlation, also after the second interview. There is no vaccine available for the prevention of HCV infection, and prophylactic immunoglobulin therapy has no proven value for primary exposure.

Adult↗

Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy.

Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy.

Antigens, Viral↗

Hepatic amino acid metabolism during hyperinsulinemia and hyperaminoacidemia in conscious rabbit during late pregnancy.

To test whether pregnancy has any effect on amino acid metabolism, we examined in two experimental conditions (1) the effect of hyperinsulinemia on the blood concentration and net hepatic balance of amino acids, and (2) the effect of hyperaminoacidemia on the hepatic handling of amino acids. Experiments were performed in conscious virgin and pregnant rabbits after an 18-hour fast. In the first protocol (hyperinsulinemia), an increment in the plasma insulin level (approximately 45 and 20 microU/mL in the portal vein and artery, respectively) with euglycemia maintained causes a similar decrease (approximately 27% to 34%) in blood amino acid concentrations without any changes in the net hepatic uptake of amino acids in both groups of animals. The hepatic uptake of branched-chain amino acids (BCAA) was practically negligible, whereas there was a consistent uptake of gluconeogenic amino acids in pregnant and nonpregnant rabbits. In the second protocol, hyperaminoacidemia leads to a significantly lower increase in the net hepatic uptake of glycine and serine in pregnant rabbits as compared with nonpregnant rabbits. The same trend was observed for the uptake of individual BCAA, but it did not reach statistical significance. We conclude that in pregnant rabbits (1) insulin does not modify the hepatic uptake of amino acids, and its ability to suppress the release of amino acids from peripheral tissues does not seem to be affected when compared with that in nonpregnant animals, and (2) when hyperaminoacidemia occurs, a greater amount of gluconeogenic amino acids (glycine and serine) would escape the liver, suggesting a higher availability of these circulating amino acids for the fetus.

Amino Acids↗