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Biomedical subjects

John Lyons

Publications and source records attributed to John Lyons.

12 recordsLinked to original sources

A fish-based index of biotic integrity to assess intermittent headwater streams in Wisconsin, USA.

I developed a fish-based index of biotic integrity (IBI) to assess environmental quality in intermittent headwater streams in Wisconsin, USA. Backpack electrofishing and habitat surveys were conducted four times on 102 small (watershed area 1.7-41.5 km(2)), cool or warmwater (maximum daily mean water temperature > or = 22 C), headwater streams in spring and late summer/fall 2000 and 2001. Despite seasonal and annual changes in stream flow and habitat volume, there were few significant temporal trends in fish attributes. Analysis of 36 least-impacted streams indicated that fish were too scarce to calculate an IBI at stations with watershed areas less than 4 km(2) or at stations with watershed areas from 4-10 km(2) if stream gradient exceeded 10 m/km (1% slope). For streams with sufficient fish, potential fish attributes (metrics) were not related to watershed size or gradient. Seven metrics distinguished among streams with low, agricultural, and urban human impacts: numbers of native, minnow (Cyprinidae), headwater-specialist, and intolerant (to environmental degradation) species; catches of all fish excluding species tolerant of environmental degradation and of brook stickleback (Culaea inconstans) per 100 m stream length; and percentage of total individuals with deformities, eroded fins, lesions, or tumors. These metrics were used in the final IBI, which ranged from 0 (worst) to 100 (best). The IBI accurately assessed the environmental quality of 16 randomly chosen streams not used in index development. Temporal variation in IBI scores in the absence of changes in environmental quality was not related to season, year, or type of human impact and was similar in magnitude to variation reported for other IBI's.

Animals↗

Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery.

Since the discovery that activating mutations of the Ras GTPase were associated with 30% or more of human cancers, the RAF/MEK/ERK pathway has been the focus of intense drug discovery effort. Within the new class of molecularly targeted anti-cancer agents progressing through the late stages of clinical development, BAY 43-9006 and PD0325901 have shown considerable promise.

Animals↗

Adequacy of laboratory simulation of in-line skater falls.

PURPOSE: Currently most laboratory simulation of distal radius fractures and wrist injuries has been with axial limb loading or vertical drop technique. To better assess the contribution of horizontal velocity in momentum in the development of wrist injury and wrist fracture we have compared forces and fracture patterns for fall simulations involving strictly vertical impacts with those that incorporated horizontal momentum in fresh-frozen upper extremities. METHODS: The premise for testing was based on a forward fall onto the palmar surface of an outstretched arm. A 45 degrees-incline impact device was used to model the horizontal and vertical velocity components of a skater fall at a representative speed. Sled mass was 26.2 kg. A 45.5-kg vertical impact system furnished contrasting data and represented prior state-of-the-art technology. Drop heights were adjusted to compensate for discrepancy in sled mass. Measurements from either impact system included vertical and horizontal forces and kinetic energy at impact. Fracture patterns were assessed radiographically. Nine trials were conducted with the incline device and 11 trials were conducted with the vertical impact system. RESULTS: The fracture rate was substantially higher for vertical impacts versus incline impacts (82% vs 33%). The rate of carpal fractures also was higher. Vertical and horizontal forces were similar statistically although slightly greater for vertical impacts. Kinetic energy, however, was 3 times greater for incline impacts than for vertical impacts. These kinetic parameters support the argument that the incline impacts should have resulted in far greater injury. CONCLUSIONS: The data suggest horizontal momentum changes limb loading. We submit that published methods for modeling skater falls have failed to provide a true simulation of the event in question.

Acceleration↗

The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs.

BACKGROUND: Creation of protease-resistant somatostatin analogs has allowed development of these peptides as clinically useful drugs. Widespread diagnostic use of radiolabeled somatostatin analogs has enhanced interest in the binding and intracellular distribution of these peptides. The degree of drug internalization and length of drug retention may be critical for drug-induced cytotoxicity. We hypothesized that the ability of a radiolabeled peptide to bind to a cell, be internalized, and induce cytotoxicity is proportional to both the radioligand concentration and the exposure time. MATERIALS AND METHODS: To test this hypothesis, somatostatin receptor-expressing cells (IMR-32) were incubated with (111)In-pentetreotide, a sst 2 preferring somatostatin analogue. Radioligand exposure time and/or concentration were varied. RESULTS: Prolonged exposure to a fixed concentration of radioligand resulted in progressive increases in whole cell binding and internalization over time. Cells exposed to a relatively fixed number of microCi-Hr yielded constant whole cell binding and internalization. Increasing the microCi-Hr resulted in a proportionate increase in binding. Cytotoxicity was also proportional to the dose of radiation regardless of whether the exposure was internalized radiation (microCi-Hr from (111)In-pentetreotide) or from external beam radiation (cGy). CONCLUSION: Both drug exposure time and drug concentration contribute to cell binding and cytotoxicity in this model and their relative contributions are inversely related.

Biological Transport↗

Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies.

Decitabine (5-aza-2'-deoxycytidine) inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses and cytotoxicity at high doses. We evaluated, in a phase 1 study, low-dose prolonged exposure schedules of decitabine in relapsed/refractory leukemias. Patient cohorts received decitabine at 5, 10, 15, or 20 mg/m2 intravenously over one hour daily, 5 days a week for 2 consecutive weeks, doses 5- to approximately 30-fold lower than the maximum tolerated dose (MTD). There were 2 groups that also received 15 mg/m2 daily for 15 or 20 days. A total of 50 patients were treated (44 with acute myelogenous leukemia [AML]/myelodysplasia [MDS], 5 with chronic myelogenous leukemia [CML], and 1 with acute lymphocytic leukemia [ALL]), and the drug was well tolerated at all dose levels, with myelosuppression being the major side effect. Responses were seen at all dose levels. However, the dose of 15 mg/m2 for 10 days appeared to induce the most responses (11 of 17 or 65%), with fewer responses seen when the dose was escalated or prolonged (2 of 19 or 11%). There was no correlation between P15 methylation at baseline or after therapy and response to decitabine. We conclude that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses.

Adolescent↗

Decitabine: development of a DNA methyltransferase inhibitor for hematological malignancies.

Decitabine (DAC) is a small molecule nucleotide analog that is incorporated into DNA and traps human DNA methyltransferases. Although initially developed as a cytotoxic agent, low-dose DAC is enjoying a revival as a specific inhibitor of hypermethylation in cancer. DAC has activity in several hematological diseases, especially myelodysplastic syndrome, chronic myelogenous leukemia and acute myeloid leukemia. Clinical and preclinical advances are presented in this review.

Animals↗

Evidence of improved knowledge and skills after an elective rotation in a hospice and palliative care program for internal medicine residents.

There is compelling evidence that residents training in primary care need education in palliative care. Evidence for effective curricula is needed. The objective of this study was to test whether a clinical elective improves measures of knowledge and skill. Residents from three categorical training programs in internal medicine were recruited to an elective including clinical experiences in an acute hospital palliative care consultation service, on an acute hospice and palliative care unit, and in-home hospice care. A 25-question pre- and post-test and a videotaped interview with a standardized patient were used to assess communication skills and measure outcomes. Residents demonstrated a 10 percent improvement in knowledge after the four-week elective (p < 0.05). All residents demonstrated basic competency in communication skills at the end of the rotation. These results indicate that clinical rotation shows promise as an educational intervention to improve palliative care knowledge and skills in primary care residents. An important limitation of the study is that it is an elective; further studies with a required rotation and/or a control group are needed to confirm the findings.

Adult↗

Eating disorders in graduate students: exploring the SCOFF questionnaire as a simple screening tool.

The results of several studies have established the validity of the SCOFF questionnaire (a 5-question screening tool for eating disorders), but researchers need to explore further replicability using the US version in the graduate school population. In this study, the authors asked 335 graduate students attending the Northwestern student health clinic on the Chicago campus to complete a written survey anonymously. A total of 305 (91%) patients completed the survey. The sensitivity and specificity for the SCOFF was 53.3% and 93.2%, respectively. This produced a PPV (the proportion who tested positive on the screen and actually had an eating disorder) of 66.7% and an NPV (the proportion of those who tested negative on the screen and actually did not have an eating disorder) of 88.7%. More than 80% of respondents were dissatisfied with their shape and weight, with over one third having a moderate to severe body image disturbance. The SCOFF is an easy instrument to administer that health care providers can use to screen for eating disorders in the primary care setting.

Adult↗

Consultation-Liaison Psychiatry Literature Database (2003 update). Part I: Consultation - Liaison Literature Database: 2003 update and national lists.

Every day there are 10,000 scientific articles published. Since the Consultation-Liaison ("C-L") psychiatrist may be asked to consult on a patient with any medical illness, e.g., severe acute respiratory syndrome (SARS), malaria, cancer, stroke, amytrophic, lateral sclerosis, and a patient who may be on any medical drug, methods need to be developed to review the recent literature and have an awareness of key and essential current findings. At the same time, teachers need to develop a current listing of seminal papers for trainees and practitioners of this newest cross-over subspecialty of psychiatry-now called Psychosomatic Medicine. Experts selected because of their writings and acknowledged contributions to a specific clinical area or problem hope examined thousands of citations to choose those articles, chapters, books, or letters that they regard as most important to Psychosomatic Medicine. In addition, psychiatric specialists in six countries have provided their national Psychosomatic Medicine (Consultation-Liaison) lists as examples of what they regard as the most important teaching materials journals: Australia, Brazil, Greece, Mexico, Portugal, and Taiwan. It is our belief that a cogent, international, systematic review will provide the greatest success in creating a "regionally appropriate" teaching and consultation literature database with world-wide applicability. We review our current progress on this literature database and software, the technical system and data organization involved, the approach used to populate the literature system, and ongoing development plans to bring this system to the physician via mobile technologies.

Databases, Bibliographic↗