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Biomedical subjects

M Gordon

Publications and source records attributed to M Gordon.

At least 37 records · Page 2Linked to original sources

T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma.

PURPOSE: We hypothesize that cellular immunity may have a previously unrecognized role in glaucomatous optic neuropathy. The purpose of this study is to analyze subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor in peripheral blood from patients with normal pressure glaucoma (NPG) or primary open angle glaucoma (POAG) in comparison to age-matched control subjects. METHODS: In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by flow cytometry and lymphocyte proliferation was used to measure the reactive ability of T cells to phytohemagglutinin (PHA). RESULTS: The frequency of CD8(+)HLA-DR(+) lymphocytes were increased in patients with NPG (P = 0.008), and CD3(+)CD8(+) lymphocytes increased in both NPG (P = 0.03) and POAG patients (P = 0.0004). CD5(+) lymphocytes were higher only in POAG patients (P = 0.0012). In comparison to controls, the ratio of CD4(+)/CD8(+) lymphocytes was similar in both groups. The mean concentrations of sIL-2R in NPG (P = 0.011) and POAG (P = 0.0023) patients were higher than that found in control subjects although IL-2 concentrations were similar in these groups. In addition, the reactive ability of T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG (P = 0.02) and POAG patients (P=0.04). CONCLUSION: The alterations of the cellular immune system in patients with glaucoma support our hypothesis that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.

Aged↗

pH-dependent structural changes at the Heme-Copper binuclear center of cytochrome c oxidase.

The resonance Raman spectra of the aa3 cytochrome c oxidase from Rhodobacter sphaeroides reveal pH-dependent structural changes in the binuclear site at room temperature. The binuclear site, which is the catalytic center of the enzyme, possesses two conformations at neutral pH, assessed from their distinctly different Fe-CO stretching modes in the resonance Raman spectra of the CO complex of the fully reduced enzyme. The two conformations (alpha and beta) interconvert reversibly in the pH 6-9 range with a pKa of 7.4, consistent with Fourier transform infrared spectroscopy measurements done at cryogenic temperatures (D.M. Mitchell, J.P. Sapleigh, A.M.Archer, J.O. Alben, and R.B.Gennis, 1996, Biochemistry 35:9446-9450). It is postulated that the different structures result from a change in the position of the Cu(B) atom with respect to the CO due to the presence of one or more ionizable groups in the vicinity of the binuclear center. The conserved tyrosine residue (Tyr-288 in R. sphaeroides, Tyr-244 in the bovine enzyme) that is adjacent to the oxygen-binding pocket or one of the histidines that coordinate Cu(B) are possible candidates. The existence of an equilibrium between the two conformers at physiological pH and room temperature suggests that the conformers may be functionally involved in enzymatic activity.

Animals↗

The number of subunits comprising the channel formed by the T domain of diphtheria toxin.

In the presence of a low pH environment, the channel-forming T domain of diphtheria toxin undergoes a conformational change that allows for both its own insertion into planar lipid bilayers and the translocation of the toxin's catalytic domain across them. Given that the T domain contributes only three transmembrane segments, and the channel is permeable to ions as large as glucosamine(+) and NAD(-), it would appear that the channel must be a multimer. Yet, there is substantial circumstantial evidence that the channel may be formed from a single subunit. To test the hypothesis that the channel formed by the T domain of diphtheria toxin is monomeric, we made mixtures of two T domain constructs whose voltage-gating characteristics differ, and then observed the gating behavior of the mixture's single channels in planar lipid bilayers. One of these constructs contained an NH(2)-terminal hexahistidine (H6) tag that blocks the channel at negative voltages; the other contained a COOH-terminal H6 tag that blocks the channel at positive voltages. If the channel is constructed from multiple T domain subunits, one expects to see a population of single channels from this mixture that are blocked at both positive and negative voltages. The observed single channels were blocked at either negative or positive voltages, but never both. Therefore, we conclude that the T domain channel is monomeric.

Animals↗

General anesthesia in an office-based plastic surgical facility: a report on more than 23,000 consecutive office-based procedures under general anesthesia with no significant anesthetic complications.

The popularity of elective office-based plastic surgery has increased significantly over the past two decades. The continuing demand for improved aesthetic results has stimulated the development of ever more complex plastic surgical techniques. These techniques may require extended periods of operative time spent under anesthesia. Patients have come to expect an almost perfect anesthetic and surgical experience, with safety and comfort being their foremost concerns. Because of increasingly complex and lengthy operations, the authors believe that intravenous sedation, used for many years in their plastic surgery practice, is now suboptimal for most longer and complex surgical procedures. In their experience, under most circumstances, general anesthesia provides the optimal anesthetic experience for the patient, anesthesiologist, and surgeon. The authors present a consecutive 18-year study of general anesthesia in more than 23,000 procedures in an accredited, office-based plastic surgical facility that offers a very safe and uniformly pleasant anesthesia experience for patients. There were no intraoperative or postoperative deaths and no significant complications. The authors' experience differs from the common perception that general anesthesia is too risky for aesthetic surgery procedures.

Ambulatory Surgical Procedures↗

Identifying research priorities on infections in older adults: proceedings of an interdisciplinary workshop.

BACKGROUND: Infections pose a substantial burden to the health of older adults. In this report, we describe the proceedings of a workshop to formulate and prioritize research questions about infections in older adults using an interdisciplinary approach. METHODS: Researchers from four sectors (basic science, clinical sciences, health services and epidemiology/determinants of health) and representatives from various Canadian local, provincial, and federal stakeholder groups were invited to a two-day workshop. Five multi-disciplinary groups and stakeholders from each of three healthcare settings (long term, acute care and community) discussed research priorities for each of the settings. Five to ten research questions were identified for each setting. RESULTS: The research questions proposed ranged from risk factors and outcomes for different infections to the effect of nutrition on infection and the role of alternative and complementary medicine in treating infections. Health service issues included barriers to immunization, prolongation of hospital length of stay by infection, use of care paths for managing infections, and decision-making in determining the site of care for individuals with infections. Clinical questions included risk factor assessment for infection, the effectiveness of preventative strategies, and technology evaluation. Epidemiologic issues included the challenge of achieving a better understanding of respiratory infections in the community and determining the prevalence of colonization with multi-resistant bacteria. CONCLUSIONS: The questions are of direct relevance to researchers in a wide variety of fields. Bringing together a multi-disciplinary group of researchers to frame and prioritize research questions about aging is feasible, participants valued the opinions of people working in other areas.

Journal Article↗

The arthritis of inflammatory childhood myositis syndromes.

OBJECTIVE: Arthritis has been an associated finding in juvenile dermatomyositis (JDM), but its prevalence, course, and response to therapy has not been well described. We investigated the frequency, course, and clinical and radiographic features in a large cohort of patients with JDM. METHODS: The charts of 94 patients with idiopathic myositis (1984-99) were reviewed: 80 JDM, 3 juvenile polymyositis (JPM), 5 amyopathic JDM, and 6 overlap myositis syndromes. Compiled data included demographics, clinical features, a detailed description of the arthritis, investigations (radiographs, autoantibodies), course, and response to therapy. All radiographs were independently reviewed by a single radiologist. RESULTS: Sixty-one percent (95% CI 50-72%) of patients with JDM had arthritis. The arthritis was reported a median 4.5 mo (range -73.6 to 76.6 mo) after the JDM onset. When compared to patients with no arthritis, the occurrence of arthritis was not significantly related to sex, race, positive antinuclear antibody or rheumatoid factor, calcinosis, nodules, vasculitis, or Raynaud's phenomenon. The initial involvement was pauciarticular in 67% and polyarticular in 33%. In the pauci group, asymptomatic knee effusions were the predominant finding (n = 19, 58%), and in 18 patients may have been the result of steroid therapy. Two patients evolved from a pauci onset to a polyarticular course. All responded to therapy (corticosteroids; 47 were taking other medications) with remission of the arthritis within a median of 2.0 mo (range 0.1-64.5 mo). However, the arthritis recurred in 39% as the corticosteroids were tapered. Four patients with JDM eventually required corticosteroid wrist injections, with resolution of the arthritis. The arthritis was nonerosive in all cases. No patient with JPM had arthritis. Three of 5 patients with amyopathic JDM and 4 of 6 with overlap myositis syndrome had a nonerosive polyarthritis. CONCLUSION: Nonerosive arthritis involving the knees, wrists, elbows, and fingers is a frequent manifestation of JDM and other idiopathic childhood myositis. The arthritis is seen early in the course of JDM and often responds to treatment. However, the arthritis may recur with tapering of corticosteroids despite remission of the JDM. In a significant proportion of JDM cases, arthritis is the major sequela and may warrant further medical therapy or intraarticular corticosteroid injections.

Adolescent↗

Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody.

BACKGROUND: Infliximab is an anti-tumor necrosis factor alpha monoclonal antibody IgG effective in the treatment and maintenance of remission of active refractory Crohn disease and associated draining enterocutaneous fistulae. Multiple infusions of infliximab show promising results in patients with rheumatoid arthritis. Currently, there is limited clinical experience with infliximab, and no published reports exist on its use in cutaneous disorders. OBSERVATIONS: We describe 2 patients with Crohn disease and pyoderma gangrenosum and 1 patient with Crohn disease and psoriasis who were treated with infliximab for recalcitrant Crohn fistulae, with concurrent improvement in their skin diseases. CONCLUSIONS: These cases suggest that infliximab, a promising therapeutic agent for refractory Crohn disease and fistulae, may also be effective in the treatment of pyoderma gangrenosum and psoriasis associated with Crohn disease.

Adult↗

Quality of life in osteoporosis.

Osteoporotic hip, vertebral, and wrist fractures have dramatic effects on health-related quality of life. Health status instruments can be used in evaluating quality of life deficits resulting from osteoporotic fractures. Although several lengthy health status instruments exist, shorter questionnaires must be developed to promote health status assessments in routine clinical practice. The authors have developed the disease-targeted, mini-Osteoporotic Quality of Life Questionnaire (OQLQ) to be used in clinical settings. The mini-OQLQ is extremely effective because it is self-administered and quickly completed. Information collected by health-related quality of life instruments may provide new insight as to how to improve quality of life for patients with fractures. Educational efforts are needed for health care professionals to increase the credibility of assessing health status in clinical practice.

Activities of Daily Living↗

A guide to understanding long-term care insurance.

Long-term care insurance is an increasingly popular benefit that has a number of advantages for both employers and employees. This coverage can protect employee assets and retirement savings and can be offered as a tax-free benefit if the plan is qualified. The premiums can be tax-deductible to employees, and the benefit is portable, since the policy is owned by the employee.

Guidelines as Topic↗

Alzheimer's disease. To tell or not to tell.

OBJECTIVE: To evaluate reasons for telling or not telling patients about a diagnosis of Alzheimer's disease and to assess the effect of such a decision on patients, families, physicians, and the health care system. QUALITY OF EVIDENCE: MEDLINE was searched from January 1966 to December 1999 using the key words "Alzheimer's disease" or "dementia" and "truth disclosure" or "attitude to health." There were no randomized controlled trials (level I evidence) in the literature. Articles identified provided level II evidence (case-controlled and cross-sectional studies) or level III evidence (expert opinion). All articles identified were chosen for this study. MAIN MESSAGE: In attempting to determine whether or not to communicate a diagnosis of Alzheimer's disease, physicians face a predicament: the desire to communicate honestly and directly with a patient is sometimes at variance with the equally compelling desire to concur with the patient's family's reluctance to disclose the diagnosis. Most Alzheimer's patients should be told of their diagnosis, but the timing of the discussion and the way it occurs are crucial to a good outcome. Most patients accept the information without a catastrophic response. Physicians must gain support from patients' families because it could take time for them to accept disclosure of what is perceived as a "hopeless" diagnosis. CONCLUSION: We must continue to support Alzheimer's patients and promote hope.

Aged↗

Ethical challenges in geriatrics and long-term care.

BACKGROUND: The Canadian population, like that of other western countries, is aging. OBJECTIVE: To review ethical issues related to clinical practice, research, and resource allocation in the geriatric and long-term care population. METHODS: Through the use of case histories and relevant literature review, we explore issues in geriatrics and long-term care. CONCLUSIONS: It is incumbent on health-care providers involved in geriatrics and long-term care to be sensitive to the ethical issues that surround decision-making in the later years of life. It is through this process that we can be humane professionals in a caring society.

Aged↗

Challenges of an aging population.

With the growing number of elderly persons in the developed world, the need for adequate health care, and social and financial resources will increase. Health and social-service professionals must be aware of the clinical and ethical issues involved. As medical advances in the treatment of debilitating conditions such as dementia, stroke, Parkinson's disease, depression, and osteoporosis are made, it is expected that the elderly will have a greater potential for longer and more fulfilling lives. Medical schools must take steps to ensure that all physicians understand the issues related to aging so that they can meet the challenges ethically, humanely, and respectfully.

Aged↗

In long-term care, the "R" in CPR is not for resurrection.

OBJECTIVE: To determine whether the concept of the "R" in CPR (cardiopulmonary resuscitation) not meaning resurrection as opposed to resuscitation is a useful explanation to families of patients in long-term care why CPR may not be recommended. METHODS: A review of the relevant literature and such ideas as futility was used to develop the conceptual basis for the discussion. CONCLUSION: There is enough evidence to support the position that for the frail, elderly, long-term care patient, the concept of resurrection rather than resuscitation can be a useful explanation to families why CPR should not be attempted in most circumstances.

Aged↗

An extralemniscal component of the mustached bat inferior colliculus selective for direction and rate of linear frequency modulations.

Frequency modulations (FMs) are prevalent in human speech, and are important acoustic cues for the categorical discrimination of phonetic contrasts. For bats, FM sweeps are also important for communication and are often the only component in echolocation calls. Auditory neurons tuned to the direction and rate of FM might underlie the encoding of rapid frequency transitions. In the mustached bat, we have discovered a population of such FM selective cells in an area interposed between the central nucleus of the inferior colliculus (ICC) and the nuclei of the lateral lemniscus (NLL). We believe this area to be the ventral extent of the external nucleus of the inferior colliculus (ICXv). To describe FM selectivity of neurons in the ICXv and to compare it to other midbrain nuclei, up- and down-sweeping linear FM stimuli were presented at different modulation rates. Extracellular recordings were made from 171 single units in the ICC, ICXv, and NLL of 10 mustached bats. In the ICXv, there was a much higher degree of FM selectivity than in ICC or NLL and a consistent preference for upward over downward FM sweeps. Anterograde and retrograde transport was examined following focal injections of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) into ICXv. The main targets of anterograde transport were the deep layers of the superior colliculus and the suprageniculate division of the medial geniculate body. The primary site of retrograde transport was the nucleus of the central acoustic tract in the brainstem. Thus, the ICXv appears to be a part of the central acoustic tract, an extralemniscal pathway linking the auditory brainstem directly to a multimodal nucleus of the thalamus.

Acoustic Stimulation↗

Smoke alarm: a review of the clinical impact of smoking on women.

This article is a review of the health impacts of smoking on women and their newborns, with an overview of the prevalence of smoking, mortality statistics, and costs. Over 50 disorders related to smoking are identified. These include many chronic and severe problems that are often overshadowed by the more well-known impacts of cancer and cardiac disease. Female impacts of smoking include two-fold rates of ectopic pregnancy, premature delivery, and low-birthweight infants; earlier menopause; pelvic-floor disorders, including urinary incontinence; menstrual disturbances; decreased fertility; greater risk of oral contraceptive failure; and babies with increased rates of sudden infant death syndrome, asthma, and attention-deficit disorders. From a clinical perspective, one in five women is addicted to nicotine. In addition, women smokers experience a stronger response to nicotine and incur higher rates of lung cancer and cardiovascular disease than their male counterparts.

Journal Article↗

Purification of plasmid DNA by tangential flow filtration.

A simple, scalable method for purification of plasmid DNA is described. The method includes modification of the classical alkaline-lysis-based plasmid extraction method by extending the solubilization step from less than 30 min to 24 h. The extraction is followed by the novel use of tangential flow filtration (TFF) for purification of the remaining contaminants. The method does not include the use of any organic solvents, RNase, high-speed centrifugation, or column chromatography steps. The method typically yields 15 to 20 mg of plasmid DNA per liter of bacterial culture and results in removal of >99% of RNA and >95% of the protein that remains after the modified alkaline lysis procedure. The procedure has been demonstrated to be effective in the isolation of seven different plasmids. Plasmids isolated using this method had comparable transfection capability relative to plasmid isolated using a classical, cesium chloride gradient-based method.

Cell Line↗