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Biomedical subjects

G M Jensen

Publications and source records attributed to G M Jensen.

At least 19 recordsLinked to original sources
PubMed2001

Cunninghamella bertholletiae infection in a bone marrow transplant patient: amphotericin lung penetration, MIC determinations, and review of the literature.

Infections caused by Cunninghamella bertholletiae, an opportunistic fungal organism, have an extremely high mortality rate. A fatal case of C. bertholletiae fungal pneumonia occurred in a man who had received an allogeneic bone marrow transplant. Aggressive debridement and high-dose liposomal amphotericin B failed to eradicate the infection. Right lung tissue samples obtained during lobectomy were assayed for amphotericin B concentrations by high-performance liquid chromatography, and minimum inhibitory concentration (MIC) determinations of amphotericin B against C. bertholletiae were determined by the macrobroth dilution method. The MIC for the isolate of C. bertholletiae was 4 microg/ml. Amphotericin B lung concentrations averaged 9.5 microg/ml (range 3.7-13.8 microg/ml), with a corresponding serum trough concentration of 0.9 microg/ml. To our knowledge, this is the first reported case of amphotericin B concentrations measured at the site of infection in a patient with a pulmonary Cunninghamella infection, together with a corresponding MIC of the organism. The patient's death, which occurred despite aggressive debridement and high amphotericin B lung concentrations, highlights the need for novel strategies to treat infections caused by invasive molds such as C. bertholletiae.

Amphotericin B↗
PubMed2001

Reflections on building community: a different perspective on academic-community partnerships using the integration matrix.

Implementation of interdisciplinary rehabilitation services and clinical training in community settings is a complex process. Documented methods for analyzing, evaluating and monitoring the process within federally funded grant projects are limited. This paper reports on the use of one proposed method, the Integration Matrix of Konrad, as a framework for formative assessment and analysis of project operations. Based upon ongoing experiences implementing a Health Resources and Services Administration (HRSA) funded clinical training program in a community setting, a revision of the Integration Matrix is proposed to better reflect a community-centered, pervasive communication approach to program operations and analysis.

Academic Medical Centers↗
PubMed2000

Expert practice in physical therapy.

BACKGROUND AND PURPOSE: The purpose of this qualitative study was to identify the dimensions of clinical expertise in physical therapy practice across 4 clinical specialty areas: geriatrics, neurology, orthopedics, and pediatrics. SUBJECTS: Subjects were 12 peer-designated expert physical therapists nominated by the leaders of the American Physical Therapy Association sections for geriatrics, neurology, orthopedics, and pediatrics. METHODS: Guided by a grounded theory approach, a multiple case study research design was used with each of the 4 investigators studying 3 therapists working in one clinical area. Data were obtained through nonparticipant observation, interviews, review of documents, and analysis of structured tasks. Videotapes made during selected therapist-patient treatment sessions were used as a stimulus for the expert therapist interviews. Data were transcribed, coded, and analyzed through the development of 12 case reports and 4 composite case studies, one for each specialty area. RESULTS: A theoretical model of expert practice in physical therapy was developed that included 4 dimensions: (1) a dynamic, multidimensional knowledge base that is patient-centered and evolves through therapist reflection, (2) a clinical reasoning process that is embedded in a collaborative, problem-solving venture with the patient, (3) a central focus on movement assessment linked to patient function, and (4) consistent virtues seen in caring and commitment to patients. CONCLUSION AND DISCUSSION: These findings build on previous research in physical therapy on expertise. The dimensions of expert practice in physical therapy have implications for physical therapy practice, education, and continued research.

Clinical Competence↗
PubMed1999

Describing expert practice in physical therapy.

In this article, the authors demonstrate how grounded theory may be used to develop models for understanding clinical practice. Through a series of research studies involving novice, experienced, and expert physical therapy practitioners, conceptual frameworks were continually revised based on data obtained from returning to the field and relevant literature available at the time. As concepts and relationships moved to larger themes, a theoretical framework for expertise in clinical practice was proposed. Current work on verifying the theoretical framework continues. Grounded theory is an excellent research approach to bound and help guide a multistage research program involving multiple researchers working in multiple settings.

Humans↗
PubMed1999

Nature of clinical practice for specialists in orthopaedic physical therapy.

Clinical specialization is part of physical therapy's continued development as a profession. Clinical specialization in physical therapy has evolved with little discussion of how specialization is related to the development of professional expertise. The purposes of this paper were to compare the identified clinical competencies in orthopaedic physical therapy to selected clinical reasoning models and expertise development models in physical therapy and interpret these comparisons in light of current theoretical work in expertise. Descriptive content analysis using results from the 1993 Practice Analysis for Orthopaedic Physical Therapy Certified Specialists was done to link attributes identified in 3 selected theoretical models of clinical decision making and practice. Survey materials were linked to theories by use of a binary index (yes/no) of whether theoretical concepts were present or absent in the survey results. The attributes that characterize an expert physical therapy practitioner involve clinical reasoning, and the ability to teach patients. The skills of a master clinician were based not just on the application of knowledge, but also on thinking and reasoning that occurs with experience. We propose that knowledge is gained through the clinician's thinking and reasoning during practice which results in a transformation or change in the clinician's knowledge base. Describing the clinical specialization process in the context of expert theory provides a strong foundation for the specialization process in physical therapy.

California↗
PubMed1999

The clinical doctorate: a framework for analysis in physical therapist education.

This article explores major considerations for analysis and discussion of the role of the clinical doctorate as the first professional degree in physical therapist education (DPT). A process for this analysis is posed based on a conceptual framework developed by Stark, Lowther, Hagerty, and Orczyk through grounded theory research on professional education. External influences from society and the profession, institutional and programmatic influences, and articulation of critical dimensions of professional competence and professional attitudes as major categories are discussed in relation to the DPT. A series of questions generated from the application of the model are put forth for continued discussion and deliberation concerning the DPT. We conclude that the DPT provides the best pathway to serve society, the patient, and the profession.

Clinical Competence↗
PubMed1998

Secretory pathways in Salmonella Typhimurium-induced fluid accumulation in the porcine small intestine.

The involvement of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors and prostaglandin E2 (PGE2) in Salmonella Typhimurium-induced fluid accumulation in the porcine small intestine was investigated. Salmonella Typhimurium (10(8) and 10(10) cfu) and cholera toxin (CT; 20 microg) were instilled for 8 and 11 h in ligated loops in the porcine jejunum and ileum. Fluid accumulation and concentrations of Na+, K+, Cl-, 5-HT and PGE2 in the fluid accumulated in the loops were measured. The fluid accumulation was also measured when Salmonella Typhimurium (10(10) cfu) and CT (20 microg) were instilled for 8 h in ligated loops in jejunum and ileum in pigs given subcutaneous injections of saline or the 5-HT3 receptor antagonist ondansetron (200 microg/kg). Salmonella Typhimurium (10(10) cfu) and CT both induced fluid accumulation in jejunum and ileum after 8 and 11 h. Both treatments also induced an increase in luminal release of 5-HT and PGE2. The accumulated fluid was iso-osmotic and hyperosmotic in CT- and Salmonella Typhimurium-treated loops, respectively. Ondansetron reduced the Typhimurium-induced fluid accumulation in both jejunum and ileum by c. 40%, while it failed to reduce the response to CT. These results demonstrate that 5-HT and PGE2 are released and 5-HT3 receptors activated in the secretory pathway of Typhimurium in the porcine small intestine.

Analysis of Variance↗
PubMed1997

Effect of ondansetron on Salmonella typhimurium-induced net fluid accumulation in the pig jejunum in vivo.

Two major pathophysiological mechanisms explaining the diarrhoea induced by Salmonella typhimurium have been suggested to be: (a) invasion of the intestine by the bacteria, and (b) an enterotoxin resembling Vibrio cholerae toxin. Cholera toxin is a potent secretagogue in pig small intestine and induces secretion partly by activating 5-hydroxytryptamine receptors, following release of 5-hydroxytryptamine. Ondansetron is a selective 5-hydroxytryptamine-3 receptor antagonist, which reduces the cholera toxin-evoked fluid accumulation in pig jejunum. The aim of this study was to investigate the effect of ondansetron on Salmonella typhimurium-induced fluid accumulation in ligated loops of pig jejunum in vivo. 10(10) colony-forming units of the bacteria was injected into loops and incubated for 8 hr. 200 mg x kg-1 ondansetron given subcutaneously reduced the Salmonella typhimurium-induced fluid accumulation by about 40%. This results suggests the involvement of 5-hydroxytryptamine and 5-hydroxytryptamine-3 receptors in Salmonella typhimurium-induced diarrhoea.

Animals↗
PubMed1997

The effect of high altitude and other risk factors on birthweight: independent or interactive effects?

OBJECTIVES: This study examined whether the decline in birth-weight with increasing altitude is due to an independent effect of altitude or an exacerbation of other risk factors. METHODS: Maternal, paternal, and infant characteristics were obtained from 3836 Colorado birth certificates from 1989 through 1991. Average altitude of residence for each county was determined. RESULTS: None of the characteristics related to birthweight (gestational age, maternal weight gain, parity, smoking, prenatal care visits, hypertension, previous small-for-gestational-age infant, female newborn) interacted with the effect of altitude. Birthweight declined an average of 102 g per 3300 ft (1000 m) elevation when the other characteristics were taken into account, increasing the percentage of low birthweight by 54% from the lowest to the highest elevations in Colorado. CONCLUSIONS: High altitude acts independently from other factors to reduce birthweight and accounts for Colorado's high rate of low birthweight.

Adult↗
PubMed1996

Altering substrate specificity at the heme edge of cytochrome c peroxidase.

Two mutants of cytochrome c peroxidase (CCP) are reported which exhibit unique specificities toward oxidation of small substrates. Ala-147 in CCP is located near the delta-meso edge of the heme and along the solvent access channel through which H2O2 is thought to approach the active site. This residue was replaced with Met and Tyr to investigate the hypothesis that small molecule substrates are oxidized at the exposed delta-meso edge of the heme. X-ray crystallographic analyses confirm that the side chains of A147M and A147Y are positioned over the delta-meso heme position and might therefore modify small molecule access to the oxidized heme cofactor. Steady-state kinetic measurements show that cytochrome c oxidation is enhanced 3-fold for A147Y relative to wild type, while small molecule oxidation is altered to varying degrees depending on the substrate and mutant. For example, oxidation of phenols by A147Y is reduced to less than 20% relative to the wild-type enzyme, while Vmax/e for oxidation of other small molecules is less affected by either mutation. However, the "specificity" of aniline oxidation by A147M, i.e., (Vmax/e)/Km, is 43-fold higher than in wild-type enzyme, suggesting that a specific interaction for aniline has been introduced by the mutation. Stopped-flow kinetic data show that the restricted heme access in A147Y or A147M slows the reaction between the enzyme and H202, but not to an extent that it becomes rate limiting for the oxidation of the substrates examined. The rate constant for compound ES formation with A147Y is 2.5 times slower than wild-type CCP. These observations strongly support the suggestion that small molecule oxidations occur at sites on the enzyme distinct from those utilized by cytochrome c and that the specificity of small molecule oxidation can be significantly modulated by manipulating access to the heme edge. The results help to define the role of alternative electron transfer pathways in cytochrome c peroxidase and may have useful applications in improving the specificity of peroxidase with engineered function.

Catalysis↗
PubMed1996

Circular dichroism and x-ray spectroscopies of Azotobacter vinelandii nitrogenase iron protein. MgATP and MgADP induced protein conformational changes affecting the [4Fe-4S] cluster and characterization of a [2Fe-2S] form.

Nucleotide interactions with nitrogenase are a central part of the mechanism of nitrogen reduction. Previous studies have suggested that MgATP or MgADP binding to the nitrogenase iron protein (Fe protein) induce protein conformational changes that control component protein docking, interprotein electron transfer, and substrate reduction. In the present study, we have investigated the effects of MgATP or MgADP binding to the Azotobacter vinelandii nitrogenase Fe protein on the properties of the [4Fe-4S] cluster using circular dichroism (CD) and x-ray absorption spectroscopies. Previous CD and magnetic CD studies on nitrogenase Fe protein suggested that binding of either MgATP or MgADP to the Fe protein resulted in identical changes in the CD spectrum arising from transitions of the [4Fe-4S]2+ cluster. We present evidence that MgADP or MgATP binding to the oxidized nitrogenase Fe protein results in distinctly different CD spectra, suggesting distinct changes in the environment of the [4Fc-4S] cluster. The present results are consistent with previous studies such as chelation assays, electron paramagnetic resonance, and NMR, which suggested that MgADP or MgATP binding to the nitrogenase Fe protein induced different conformational changes. The CD spectrum of a [2Fe-2S]2+ form of the nitrogenase Fe protein was also investigated to address the possibility that the MgATP- or MgADP-induced changes in the CD spectrum of the native enzyme were the result of a partial conversion from a [4Fe-4S] cluster to a [2Fe-2S] cluster. No evidence was found for a contribution of a [2Fe-2S]2+ cluster to the CD spectrum of oxidized Fe protein in the absence or presence of nucleotides. A novel two-electron reduction of the [2Fe-2S]2+ cluster in Fe protein was apparent from absorption, CD, and electron paramagnetic resonance data. Fe K-edge x-ray absorption spectra of the oxidized Fe protein revealed no changes in the structure of the [4Fe-4S] cluster upon MgATP binding to the Fe protein. The present results reveal that MgATP or MgADP binding to the oxidized state of the Fe protein result in different conformational changes in the environment around the [4Fe-4S] cluster.

Absorptiometry, Photon↗
PubMed1996

Effect of 5-HT2 and 5-HT3 receptor antagonists on cholera toxin-induced fluid hypersecretion in the pig jejunum.

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. The aim of this study was to determine the effect of the 5-hydroxytryptamine receptor antagonists ketanserin, granisetron, ondansetron and tropisetron on cholera toxin-induced hypersecretion in the pig jejunum. Hypersecretion was induced by cholera toxin in ligated jejunal loops. The antagonists were administered subcutaneously at a dose of 100 micrograms/kg. Furthermore, the effect of intraluminally instilled ondansetron was studied. None of the antagonists altered basal absorption or caused fluid hypersecretion. Cholera toxin caused a dose-dependent electrolyte and fluid hypersecretion. The apparent maximal effect, 6.8 +/- 0.4 mg fluid x mg dry loop-1, was reduced by ondansetron, granisetron and tropisetron by about 40%, 30%, and 20%, respectively, whereas ketanserin had no effect. Intraluminal ondansetron reduced the effect of cholera toxin by about 50%. These results demonstrate that 5-hydroxytryptamine3 antagonists administered subcutaneously reduce the cholera toxin-induced hypersecretion in the pig jejunum. Finally, the results support species differences with respect to the antagonistic effect of the tested drugs in cholera toxin-induced hypersecretion.

Analysis of Variance↗
PubMed1995

The role of aspartate-235 in the binding of cations to an artificial cavity at the radical site of cytochrome c peroxidase.

The activated state of cytochrome c peroxidase, compound ES, contains a cation radical on the Trp-191 side chain. We recently reported that replacing this tryptophan with glycine creates a buried cavity at the active site that contains ordered solvent and that will specifically bind substituted imidazoles in their protonated cationic forms (Fitzgerald MM, Churchill MJ, McRee DE, Goodin DB, 1994, Biochemistry 33:3807-3818). Proposals that a nearby carboxylate, Asp-235, and competing monovalent cations should modulate the affinity of the W191G cavity for ligand binding are addressed in this study. Competitive binding titrations of the imidazolium ion to W191G as a function of [K+] show that potassium competes weakly with the binding of imidazoles. The dissociation constant observed for potassium binding (18 mM) is more than 3,000-fold higher than that for 1,2-dimethylimidazole (5.5 microM) in the absence of competing cations. Significantly, the W191G-D235N double mutant shows no evidence for binding imidazoles in their cationic or neutral forms, even though the structure of the cavity remains largely unperturbed by replacement of the carboxylate. Refined crystallographic B-values of solvent positions indicate that the weakly bound potassium in W191G is significantly depopulated in the double mutant. These results demonstrate that the buried negative charge of Asp-235 is an essential feature of the cation binding determinant and indicate that this carboxylate plays a critical role in stabilizing the formation of the Trp-191 radical cation.

Aspartic Acid↗
PubMed1994

Construction of a bisaquo heme enzyme and binding by exogenous ligands.

The crystal structure of the His-175-->Gly (H175G) mutant of cytochrome-c peroxidase (EC 1.11.1.5), missing its only heme ligand, reveals that the histidine is replaced by solvent to give a bisaquo heme protein. This protein retains some residual activity, which can be stimulated or inhibited by addition of exogenous ligands. Structural analysis confirms the binding of imidazole to the heme at the position of the wild-type histidine ligand. This imidazole complex reacts readily with hydrogen peroxide to produce a radical species with novel properties. However, reactivation in this complex is incomplete (approximately 5%), which, in view of the very similar structures of the wild-type and the H175G/imidazole forms, implies a critical role for tethering of the axial ligand in catalysis. This study demonstrates the feasibility of constructing heme enzymes with no covalent link to the protein and with unnatural ligand replacements. Such enzymes may prove useful in studies of electron transfer mechanisms and in the engineering of novel heme-based catalysts.

Crystallography, X-Ray↗
PubMed1994

Calculation of the redox potentials of iron-sulfur proteins: the 2-/3-couple of [Fe4S*4Cys4] clusters in Peptococcus aerogenes ferredoxin, Azotobacter vinelandii ferredoxin I, and Chromatium vinosum high-potential iron protein.

Calculations of the redox potentials of the 2-/3-couples of [Fe4S*4Cys4] clusters in the iron-sulfur proteins Peptococcus aerogenes ferredoxin (PaFd), Azotobacter vinelandii ferredoxin I (AvFdI) and Chromatium vinosum high potential iron protein (CvHiPIP) based on the Protein Dipoles Langevin Dipoles (PDLD) method are reported. The structures of these proteins have been determined by X-ray crystallography; in the case of PaFd the structure has recently been revised due to a change in the sequence close to Cluster II. The large differences between the potentials of the [Fe4S*4Cys4] clusters of PaFd and AvFdI and the potential of the [Fe4S*4Cys4] cluster of CvHiPIP are successfully modeled and originate principally in differences in the configuration of main-chain amide groups near the clusters. The small difference between the potentials of PaFd and AvFdI is also satisfactorily modeled in the case of Cluster I of PaFd. Solvent dipoles close to the cluster in PaFd are an important contributor to its higher potential. The two X-ray structures of PaFd yield similar results for Cluster I of PaFd. In contrast, the results for Cluster II differ substantially; for reasons not yet clear, the recently revised structure leads to results in worse agreement with experiment.

Amino Acid Sequence↗
PubMed1994

Promoting patient cooperation with exercise programs: linking research, theory, and practice.

Managing patient-nonadherence with prescribed exercise regimens is not an uncommon task for physical therapists working with individuals with arthritis. Yet little is known about the factors that influence patient adherence with exercise programs or therapist knowledge and use of theoretically based adherence management techniques. Survey research with physical therapists and patients was used to provide a database for further insight into the barriers experienced in implementing exercise programs in clinical practice. In this paper, we suggest that the cooperation with an exercise regimen is mediated by the patient's belief system and requires a therapeutic process of mutual inquiry, problem solving, and negotiation between the therapist and patient. Concepts from research, theory, and practice are integrated into a Process Model for Patient-Practitioner Collaboration for use in clinical practice.

Adult↗