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Biomedical subjects

G Gordon

Publications and source records attributed to G Gordon.

At least 37 records · Page 2Linked to original sources

Developing a cost accounting system for a physician group practice.

Physicians in group practices must gain a competitive edge to survive in a healthcare environment in which cost efficiency has become critical to success. One tool that can help them is a cost accounting system that yields reliable, detailed data on the costs of delivering care. Such a system not only can enable physicians and group administrators to manage their operations more cost-effectively, but also can help them accurately assess the potential profitability of prospective managed care plans. An otolaryngology practice located in Mississippi provides a model for developing a cost accounting system that can be applied to physician group practices.

Accounting↗

Lack of persistence of E1- recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs.

Two recombinant adenoviruses expressing either human alpha 1-antitrypsin (hAAT) or canine factor IX (cFIX) were modified so that they also contained a temperature-sensitive mutation (ts125) in the DNA binding protein encoded within the viral E2A region. The effects of the inclusion of the ts125 mutation on transgene expression in vivo were evaluated in Balb/c mice and hemophilia B dogs by comparison with adenoviral vectors containing the same transgene but lacking the ts125 mutation. No significant differences in the duration of transgene expression were observed in either animal model. Insufficiency of the ts125 mutation in the prolongation of transgene expression in these two animal models suggests that further modification of the vector backbone may be required to achieve long-term gene expression in a wide variety of applications. Additionally, humoral immune response to transgene products has been demonstrated in immunocompetent animal models, which will also need to be surmounted for long-term efficacy in disease treatment by gene therapy.

Adenoviridae↗

Effects of variations in flow on aortic valve area in aortic stenosis based on in vivo planimetry of aortic valve area by multiplane transesophageal echocardiography.

This study provides evidence that acute changes in stroke volume and cardiac output do not result in significant alterations in the anatomic AVA measured with multiplane TEE in patients with AS of moderate or severe degree. Thus, TEE could be useful in the assessment of severity of AS in both low- and high-output states.

Adult↗

On the mechanism of interaction of steroids with human glucose 6-phosphate dehydrogenase.

Previous studies have demonstrated that certain 17- and 20-ketosteroids are potent inhibitors of the NADP-linked oxidation of glucose 6-phosphate by mammalian glucose 6-phosphate dehydrogenases. This inhibition is uncompetitive with respect to both NADP+ and glucose 6-phosphate. In order to elucidate the detailed mechanism of this rare type of inhibition, we examined the effects of steroids on human glucose 6-phosphate dehydrogenase catalyzing the reverse reaction, i.e., the reduction of the gluconolactone by NADPH. To circumvent problems associated with the known instability of 6-phospho-delta-gluconolactone, the natural product of glucose 6-phosphate oxidation, the more stable 6-phospho-gamma-gluconolactone was used. Dehydroepiandrosterone, epiandrosterone, 16 alpha-bromoepiandrosterone, and dehydroepiandrosterone sulfate all inhibited the reverse reaction uncompetitively with respect to both NADPH and the gamma-lactone. The Ki values for each of these steroids, determined by varying either coenzyme or substrate in both the forward and the reverse reactions, are very similar. These results demonstrate that steroids inhibit glucose 6-phosphate dehydrogenase by binding to the ternary enzyme-coenzyme-substrate ternary complex(es). This is the first direct demonstration that uncompetitive inhibition of a two-substrate enzyme, by compounds other than its substrates or products, can occur by binding of the inhibitor to a ternary enzyme complex.

Dehydroepiandrosterone↗

Gene therapy for hemophilia B: host immunosuppression prolongs the therapeutic effect of adenovirus-mediated factor IX expression.

Hemophilia B is caused by a deficiency of blood clotting factor IX (FIX). Previous studies have shown that the delivery of a recombinant adenoviral vector expressing canine FIX (cFIX) resulted in a complete correction of hemophilia B in FIX-deficient dogs, but that cFIX expression decreased to only about 1-2% of normal levels 3 weeks after treatment. In the present study, therapeutic levels of cFIX expression capable of producing a partial correction of hemophilia B were maintained for at least 6 months after the coadministration of the cFIX-expressing adenovirus and the immunosuppressive agent cyclosporin A (CsA). These findings support a recent report (Yang et al., 1994) that host T-cell-mediated immunity against virally transduced cells is a major contributing factor to the transient nature of adenovirus-mediated gene expression in immunocompetent animals. Although a second administration of the cFIX-expressing adenovirus 6 months after the first infusion had only a minimal effect on plasma FIX levels in a dog that had been continuously treated with CsA, the prolonged expression of the transgene indicates that immunosuppression may be applicable in attaining long-term treatment of clinically relevant disorders.

Adenoviridae↗

Invasive otitis externa due to Aspergillus species: case report and review.

Aspergillus flavus, an unusual cause of malignant external otitis, was identified in pure culture of tissue from two patients in which histologic examinations demonstrated branching septate hyphae invading the temporal bone. Both patients presented with protracted external ear pain. Multiple attempts at treatment with topical agents (polymyxin B sulfate-neomycin sulfate-hydrocortisone), oral agents (cephalexin and ciprofloxacin), and parenteral agents (ceftazidime and tobramycin) were unsuccessful before definitive diagnosis was made. Treatment with amphotericin B, followed by a more protracted course of itraconazole, resulted in an apparent cure for these patients. Follow-up examination at 15 months after the discontinuation of therapy with itraconazole demonstrated no recurrence of infection. Previously reported cases have predominantly involved immunocompromised persons, and these cases are summarized.

Aged↗

Transesophageal echocardiography for hemodynamic management of thoracoabdominal aneurysm repair.

Maintenance of cardiovascular stability during thoracoabdominal aneurysm repair remains a formidable challenge. Transesophageal echocardiography (TEE) has been shown to be an excellent method for detecting myocardial ischemia and assessing left ventricular volume. We examined the utility of TEE in a group of 17 patients from an overall series of 33 patients who underwent thoracoabdominal aneurysm resection between 1988 and 1992. The mortality rate was 9%, whereas the incidences of myocardial infarction and paraplegia were 13% and 6%, respectively. Intraoperative management was significantly altered by TEE data in nine patients. Two patients were noted to have mitral valve insufficiency, and one had transient ischemia-induced regional wall abnormalities. In six patients, Swan-Ganz-derived filling data failed to identify severe hemodynamic alterations that were noted on TEE. Five patients were hypovolemic and hyperdynamic, whereas one was in florid congestive heart failure. Further investigation is warranted to prospectively validate this technique.

Adult↗

A community-based approach to HIV case management: systematizing the unmanageable.

This article presents an analysis and typology of community-based care for a young Hispanic mother with acquired immune deficiency syndrome (AIDS). It develops a conceptual framework that examines retrospectively the needs generated by AIDS over time, the appropriateness of the services, and an assessment of the interventions. Community-based case management can effectively address some of the diverse and changing needs of AIDS patients and their families, such as bridging service gaps and fortifying patient and system strengths while minimizing their weaknesses. Community-based case managers may also be better equipped than hospital case managers to work with difficult patients and coordinate community- and hospital-based care. Conclusions are presented regarding the definition and implementation of community-based, culturally sensitive, family-centered human immunodeficiency virus case management, as well as the importance and difficulty of developing relationships among the family, health care providers, and institutions within the community.

Acquired Immunodeficiency Syndrome↗

Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial.

OBJECTIVE: To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A tertiary acute-care 500-bed university teaching hospital. PATIENTS: Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. INTERVENTIONS: Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. RESULTS: Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.

Adult↗

Corticofugal actions on lemniscal neurons of the cuneate, gracile and lateral cervical nuclei of the cat.

Extracellular records were made from single identified lemniscal neurons of the cell-cluster regions of the cuneate and gracile nuclei, and of the lateral cervical nucleus, in pentobarbitone-anaesthetized cats. Forepaw, hind paw or face regions of the contralateral Sm I cortex were identified by recording through an inserted microelectrode which was then used for stimulation. The effect of a double cortical shock or train of shocks was usually inhibition: occasionally facilitation was observed, or mixed effects with facilitation preceding inhibition. Effects were seen in about half the cells studied in all three nuclei. Some cells of the lateral cervical nucleus were strongly excited, an effect not seen in the other nuclei. No component of these responses depended on suprathreshold stimulus intensities. Some lateral cervical cells were studied after deafferentiation by section of the dorsolateral spinal white matter; the same pattern of effects was seen. With an upper stimulus limit of 200 microA, cuneate but not gracile cells were affected from the cortical forepaw region, and gracile but not cuneate cells from the hind paw region. With threshold stimuli in an identified part of the forepaw cortical representation it was clear that cuneate cells with cutaneous receptive fields in corresponding parts of the forepaw had the lowest thresholds (minimum 6 microA). Threshold rose steeply with distance across the paw, suggesting quite sharp focusing of corticofugal effects in this system. When using similar procedures with the lateral cervical nucleus, with an upper limit of 200 microA, stimulation of forelimb cortex, or of facial cortex, affected both neurons with forelimb and those with hind limb fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transforming growth factor alpha and atrial natriuretic peptide in white adipose tissue depots in rats.

To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague-Dawley rats were separated into adipocyte and stroma-vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose-response curves for angiotensin-converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma-vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor-alpha (TGF-alpha) concentrations were significantly greater in epididymal than perirenal stroma-vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF-alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal-vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.

Adipose Tissue↗

Multiplane transesophageal echocardiography. Imaging planes, echocardiographic anatomy, and clinical experience with a prototype phased array OmniPlane probe.

Multiplane transesophageal echocardiography is a new exciting development in echocardiography. We examined the methodology and echo-anatomic correlations of multiplane transesophageal echocardiography and its clinical applications in 100 patients. We used a 5-MHz phased array multiplane (OmniPlane) transesophageal probe. In this instrument, the transducer array can be steered through 180 degrees from any transducer location. This provides a vast assembly of imaging planes, allowing for detailed visualization of all dimensions of cardiac anatomy. This report presents our observations on the echocardiographic anatomy seen in various image planes and the unique clinical potential of multiplane transesophageal echocardiography in the diagnostic assessment of cardiovascular disorders. This technique appears to provide incremental diagnostic information that enhances the interpretative ability. Less esophageal probe manipulation is required with consequent decrease in patient discomfort. We conclude that multiplane transesophageal echocardiography enhances the versatility of transesophageal examination and offers many new avenues for developments such as three-dimensional echocardiography.

Echocardiography↗

Evidence that tetracycline analogs whose primary target is not the bacterial ribosome cause lysis of Escherichia coli.

The modes of action of atypical tetracyclines that do not directly inhibit bacterial protein synthesis were investigated. The analogs tested, chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi-anhydrochlortetracycline, were bactericidal and caused the lysis of Escherichia coli accompanied by the release of the cytoplasmic enzyme beta-galactosidase into the supernatant. Examination by electron microscopy demonstrated that cells exposed to these analogs underwent marked morphological alterations that included the formation of numerous ghosts and the appearance of cellular debris in the culture medium. Although atypical tetracyclines promoted lysis in intact organisms, they did not cause lysis of E. coli spheroplasts, indicating that the analogs do not directly destroy the cytoplasmic membrane. These agents may promote cell lysis and death by interfering with the membrane's electrochemical gradient, which in turn leads to stimulation of autolytic enzyme activity and cellular lysis. The results support recently published data which indicate that tetracyclines are divisible into two classes on the basis of their modes of action.

Bacterial Proteins↗

Clinical economics: a method for prospective health resource data collection.

Information about the economic benefit of new drugs is becoming increasingly important for formulary considerations, reimbursement policies and related considerations. Although economic benefits of drugs have been analysed and reported, the economic benefits of drugs have rarely been examined in the course of randomised therapeutic trials. We designed a modular survey instrument, the Resource Utilisation Survey (RUS), to collect economic outcomes in prospective trials. A pilot test of the RUS was conducted using clinical trial methods in a study of nizatidine versus placebo in preventing ulcers induced by nonsteroidal anti-inflammatory drugs. The purpose of the pilot study was to evaluate the RUS instrument and corresponding study design issues in clinical trials for either acute or chronic diseases. With the lessons learned from the pilot study, the RUS has been used successfully in other ongoing clinical trials.

Economics, Pharmaceutical↗