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Biomedical subjects

D A Davis

Publications and source records attributed to D A Davis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evaluating the effectiveness of 2 educational interventions in family practice.

BACKGROUND: Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor. METHODS: The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study. RESULTS: The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores. INTERPRETATION: Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.

Education, Medical, Continuing↗
PubMed1999

Durable loss of a malignant T-cell clone in a stage IV cutaneous T-cell lymphoma patient treated with high-dose interferon and photopheresis.

Stage IV cutaneous T-cell lymphoma (CTCL) has a notoriously poor prognosis and many treatment options exist. We describe the successful treatment of a case of stage IV CTCL with combination photopheresis and high-dose interferon alfa (IFNalpha). The patient was treated with combination therapy of monthly photopheresis and daily doses of IFNalpha up to 36 MU. Response to therapy was followed by clinical observation and Southern blot analysis for the detection of a malignant clone. The findings of this case were compared with others using a computer-based literature review. A complete clinical response lasting 64 months was achieved. Clinical relapse was preceded by an increase in the CD4/CD8 ratio and by reappearance of the T-cell receptor gene rearrangement. Combined photopheresis and high-dose IFNalpha led to a durable and sustained complete response in stage IV CTCL. CD4/CD8 ratios and T-cell gene rearrangements may be helpful in patient management.

Adult↗
PubMed1999

Conserved cysteines of the human immunodeficiency virus type 1 protease are involved in regulation of polyprotein processing and viral maturation of immature virions.

We investigated the role of the two highly conserved cysteine residues, cysteines 67 and 95, of the human immunodeficiency virus type 1 (HIV-1) protease in regulating the activity of that protease during viral maturation. To this end, we generated four HIV-1 molecular clones: the wild type, containing both cysteine residues; a protease mutant in which the cysteine at position 67 was replaced by an alanine (C67A); a C95A protease mutant; and a double mutant (C67A C95A). When immature virions were produced in the presence of an HIV-1 protease inhibitor, KNI-272, and the inhibitor was later removed, limited polyprotein processing was observed for wild-type virion preparations over a 20-h period. Treatment of immature wild-type virions with the reducing agent dithiothreitol considerably improved the rate and extent of Gag processing, suggesting that the protease is, in part, reversibly inactivated by oxidation of the cysteine residues. In support of this, C67A C95A virions processed Gag up to fivefold faster than wild-type virions in the absence of a reducing agent. Furthermore, oxidizing agents, such as H2O2 and diamide, inhibited Gag processing of wild-type virions, and this effect was dependent on the presence of cysteine 95. Electron microscopy revealed that a greater percentage of double-mutant virions than wild-type virions developed a mature-like morphology on removal of the inhibitor. These studies provide evidence that under normal culture conditions the cysteines of the HIV-1 protease are susceptible to oxidation during viral maturation, thus preventing immature virions from undergoing complete processing following their release. This is consistent with the cysteines being involved in the regulation of viral maturation in cells under oxidative stress.

Alanine↗
PubMed1998

The role of transcranial Doppler in nonarteritic ischemic optic neuropathy.

PURPOSE: To investigate through the use of cerebral Doppler technology whether emboli are a more common cause of nonarteritic anterior ischemic optic neuropathy (NAION) than previously recognized. METHODS: Eleven patients with a recent (<121 days) history of nonarteritic anterior ischemic optic neuropathy and 10 age-matched controls (event > 121 days) were examined using a Nicolet Pioneer 2020 transcranial Doppler (TCD) unit with a 2-MHz bilateral continuous monitoring capability. The right and left middle cerebral arteries were evaluated simultaneously for 30 minutes at a depth of 50 to 55 mm, and the number of emboli, blood flow velocities, and pulsatility indices were recorded. Data were stored by computer, and hard-copy color recordings were made. RESULTS: None of 11 patients with a recent history of NAION demonstrated microemboli by TCD examination. One patient in the control group who had a remote history of NAION had a microembolic event rate of 12 per hour (six over 30 minutes). This patient had a history of prosthetic cardiac valve replacement and was taking anticoagulation medication at the time of the examination. CONCLUSIONS: Our study did not reveal an increased incidence of embolic events in patients with NAION when they were examined in a transcranial Doppler study of the middle cerebral arteries. This study does not support embolism as a frequent cause of NAION.

Arteritis↗
PubMed1998

Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs.

OBJECTIVES: Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18 degrees C). METHODS: Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37 degrees C) controls. Pial arteriolar caliber (range = 111 to 316 microm diameter) was monitored using video microscopy. RESULTS: Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. CONCLUSIONS: The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass.

Acetylcholine↗
PubMed1998

Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus.

The activity of three human immunodeficiency virus (HIV) protease inhibitors was investigated in human primary monocytes/macrophages (M/M) chronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhibited the replication of HIV-1 in vitro, with EC50s of approximately 0.5-3.3 microM. However, only partial inhibition was achievable, even at the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was approximately 7- to 26-fold lower than in acutely infected M/M and approximately 2- to 10-fold lower than in chronically infected H9 lymphocytes. When protease inhibitors were removed from cultures of chronically infected M/M, production of virus rapidly returned to the levels found in untreated M/M. Therefore, relatively high concentrations of protease inhibitors are required to suppress HIV-1 production in chronically infected macrophages, and such cells may be a vulnerable point for the escape of virus in patients taking these drugs.

Anti-HIV Agents↗
PubMed1998

Atrophic and plaquelike dermatofibrosarcoma protuberans.

It is clinically important to realize that dermatofibrosarcoma protuberans (DFSP) often begins as a nonprotuberant plaque and occasionally persists as such. Cases of what has been called atrophic DFSP have recently been reported. None of these cases varied either histologically or prognostically from classical nodular DFSP, and all should be considered part of the clinical spectrum of DFSP. However, histologic variants of DFSP can portend a worse prognosis. The fibrosarcomatous variant, which is fascicular and does not immunostain with anti-CD34, is an example. Recently, another fascicular variant that does positively immunostain with anti-CD34 has been described as plaquelike DFSP. We described a case of a DFSP that had histologically banal, slender fascicles of anti-CD34 immunostaining spindle cells in a clinically nonprotuberant plaque despite subsequently developing a nodule with typical storiform histology. The importance of anti-CD34 immunoperoxidase staining in the diagnosis and prognosis of DFSP variants is emphasized.

Antigens, CD34↗
PubMed1998

Information about barriers to planned change: a randomized controlled trial involving continuing medical education lectures and commitment to change.

PURPOSE: To determine whether practicing physicians receiving only clinical information at a traditional continuing medical education (CME) lecture (control group) and physicians receiving clinical information plus information about barriers to behavioral change (study group) would alter their clinical behaviors at the same rate. METHOD: In a randomized controlled trial, the investigators matched 13 pairs of U.S. and Canadian medical schools, assigning one school from each pair to study or control conditions. Following the commitment-to-change model, the investigators asked the primary care physicians attending control or study lectures on the management of cardiovascular risks whether they intended to make behavioral changes as a result of participating in the lectures and, if so, to indicate the specific changes. Thirty to 45 days later, the investigators surveyed the responding physicians to learn whether they had implemented those changes. RESULTS: Information about barriers to change did not increase the likelihood that physicians in the study group would report successful changes; they were no more likely to change than those in the control group. However, the physicians in both study and control groups were significantly more likely to change (47% vs 7%, p < .001) if they indicated an intent to change immediately following the lecture. CONCLUSIONS: Successful change in practice may depend less on clinical and barriers information than on other factors that influence physicians' performances. To further develop the commitment-to-change strategy in measuring the effects of planned change, it is important to isolate and learn the powers of individual components of the strategy as well as their collective influence on physicians' clinical behaviors.

Behavior↗
PubMed1998

Human herpesvirus 8 (HHV-8) in the pathogenesis of Kaposi's sarcoma and other diseases.

The discovery of Kaposi's Sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/ HHV-8) and subsequent studies of this virus have provided a body of evidence that support the concept that this is an etiologic agent for Kaposi's sarcoma (KS). Several studies have indicated that this virus may also be a causal agent for primary effusion lymphoma (PEL) and Castleman's disease as well. First generation serologic assays for HHV-8 have now been developed. The preponderance of data suggest that the incidence of HHV-8 infection is highest in populations at risk for KS: male homosexuals, immunosuppressed patients, and those who live in endemic regions. HHV-8 encodes for functional homologs of human proteins that may play a role in the development of disease. As we learn more about the steps by which this virus can lead to KS and/or other diseases, rational therapies and preventative strategies may be possible.

Castleman Disease↗
PubMed1997

Thioltransferase (glutaredoxin) is detected within HIV-1 and can regulate the activity of glutathionylated HIV-1 protease in vitro.

Previous studies have suggested that the two conserved cysteines of the HIV-1 protease may be involved in regulating protease activity. Here, we examined diglutathionylated wild type protease (Cys-67-SSG, Cys-95-SSG) and the monoglutathionylated protease mutants (C67A, Cys-95-SSG and C95A, Cys-67-SSG) as potential substrates for thioltransferase (glutaredoxin). Time-dependent changes in the extent of deglutathionylation of each protein were assayed by reverse phase-high performance liquid chromatography. Glutathione alone was not an effective reductant, whereas thioltransferase displayed differential catalysis toward the Cys-95-SSG and Cys-67-SSG sites. At low thioltransferase concentrations (5 nM), deglutathionylation occurred almost exclusively at Cys-95-SSG. With substantially more thioltransferase (100 nM) Cys-67-SSG was partially deglutathionylated but only at 20% of the rate of Cys-95-SSG reduction. Treatment of the diglutathionylated protease with thioltransferase not only restored protease activity but generated an enzyme preparation that had a 3- to 5-fold greater specific activity relative to the fully reduced form. Immunoblot analysis of HIV-1MN virus with an antibody to thioltransferase detected a band co-migrating with recombinant thioltransferase that persisted following subtilisin treatment, indicating the presence of thioltransferase within HIV-1. Our results implicate thioltransferase in the regulation and/or maintenance of protease activity in HIV-1 infected cells.

Blotting, Western↗
PubMed1997

Translating guidelines into practice. A systematic review of theoretic concepts, practical experience and research evidence in the adoption of clinical practice guidelines.

OBJECTIVE: To recommend effective strategies for implementing clinical practice guidelines (CPGs). DATA SOURCES: The Research and Development Resource Base in Continuing Medical Education, maintained by the University of Toronto, was searched, as was MEDLINE from January 1990 to June 1996, inclusive, with the use of the MeSH heading "practice guidelines" and relevant text words. STUDY SELECTION: Studies of CPG implementation strategies and reviews of such studies were selected. Randomized controlled trials and trials that objectively measured physicians' performance or health care outcomes were emphasized. DATA EXTRACTION: Articles were reviewed to determine the effect of various factors on the adoption of guidelines. DATA SYNTHESIS: The articles showed that CPG dissemination or implementation processes have mixed results. Variables that affect the adoption of guidelines include qualities of the guidelines, characteristics of the health care professional, characteristics of the practice setting, incentives, regulation and patient factors. Specific strategies fell into 2 categories: primary strategies involving mailing or publication of the actual guidelines and secondary interventional strategies to reinforce the guidelines. The interventions were shown to be weak (didactic, traditional continuing medical education and mailings), moderately effective (audit and feedback, especially concurrent, targeted to specific providers and delivered by peers or opinion leaders) and relatively strong (reminder systems, academic detailing and multiple interventions). CONCLUSIONS: The evidence shows serious deficiencies in the adoption of CPGs in practice. Future implementation strategies must overcome this failure through an understanding of the forces and variables influencing practice and through the use of methods that are practice- and community-based rather than didactic.

Clinical Trials as Topic↗
PubMed1997

Percutaneous absorption of salicylic acid after repeated (14-day) in vivo administration to normal, acnegenic or aged human skin.

The objective of the present work was to determine the relative bioavailability of salicylic acid (SA) after repeated (14-day) topical application to subjects who presented normal, acnegenic, or photodamaged facial skin. To emulate exposure characteristics likely to be encountered by subjects in these two subpopulations, individuals presenting facial acne were treated with 2% SA in a hydroalcoholic vehicle, and volunteers with aged or photodamaged skin received a comparable topical dose of SA in a cream (moisturizer-like) vehicle. Plasma concentration-time profiles and cumulative urinary excretion of SA were measured after the last dose in subjects who had received 15 consecutive daily topical applications of 27 mg of SA or oral doses of 81 mg of acetylsalicylic acid (ASA). The rate and extent of percutaneous absorption of SA were not affected by facial skin condition. Faster rates of absorption (Cmax) were obtained with a hydroalcoholic compared with a cream vehicle. Systemic SA exposures were at least five-fold higher with oral ASA than topical SA. Based on systemic salicylate concentrations resulting from ingestion of 81 mg of ASA, these results support that patients without gross skin disorders are at minimal risk of adverse systemic effects from routine use of topical products containing 2% SA.

Acne Vulgaris↗
PubMed1997

Detection of serum antibodies to a Kaposi's sarcoma-associated herpesvirus-specific peptide.

Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) may play an etiologic role in the pathogenesis of KS. In an attempt to assess KSHV/HHV-8 infection, an ELISA was developed using an 18-amino acid peptide from a putative minor capsid protein of KSHV/HHV-8 conjugated to bovine serum albumin. Overall, sera from human immunodeficiency virus type 1 (HIV-1)-positive patients with KS had a higher reactivity in the assay than did sera from HIV-1-positive patients without KS (P = .018). Of 35 HIV-1-positive patients with KS, 60% were antibody positive, compared with 27% of 33 HIV-1-positive patients without KS. Of 30 healthy blood donors, 20% were antibody positive. The ELISA responses did not correlate with antibody titers to Epstein-Barr virus. Given the homology and antigenic relatedness between KSHV/HHV-8 and Epstein-Barr virus, serologic assays involving unique KSHV/HHV-8 peptides may prove to be valuable in defining the epidemiology and clinical expression of this virus.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Removal of human immunodeficiency virus type 1 (HIV-1) protease inhibitors from preparations of immature HIV-1 virions does not result in an increase in infectivity or the appearance of mature morphology.

The processing of gag and gag-pol polyproteins by human immunodeficiency virus type 1 (HIV-1) protease is a crucial step in the formation of infectious HIV-1 virions. In this study, we examine whether particles produced in the presence of inhibitors of HIV-1 protease can subsequently undergo gag polyprotein cleavage with restoration of infectivity following removal of the inhibitors. Viral particles produced during 7 days of culture in the presence of the protease inhibitors KNI-272 (10 microM) and saquinavir (5 microM) contained predominantly p55gag polyprotein but little or no p24gag cleavage product. Following resuspension of the particles in medium free of the inhibitor, some gag polyprotein processing was detected in particles produced from the KNI-272-treated cells, but not from the saquinavir-treated cells within the first 3 h. However, the majority of the protein remained as p55gag throughout a 48-h experimental period. The infectivity (50% tissue culture infective dose per milliliter) of the viral particles from KNI-272-treated cells was 10(6)-fold lower than that of control particles and did not significantly increase over the 48 h after the inhibitor was removed, despite the apparent return of protease function in a subset of these virions. This failure to restore infectivity was due neither to a reduction in the number of particles produced by protease inhibitor-treated cells nor to a failure of HIV RNA to be packaged in the virions. These particles also failed to express the mature phenotype by electron microscopy. Thus, while some processing of the gag polyprotein can occur in isolated HIV virions, this does not appear to be sufficient to restore infectivity in the majority of particles. This finding suggests that there may be constraints on postbudding polyprotein processing in the production of viable particles. These results should have positive implications regarding the use of protease inhibitors as anti-HIV drugs.

Blotting, Western↗
PubMed1997

Massive dystrophic calcinosis cutis secondary to chronic needle trauma.

Extensive dystrophic calcinosis cutis of the hips and anterolateral thighs in a woman with insulin-dependent diabetes mellitus is described. Clinical, histologic, and radiographic data are provided to familiarize the reader with this unique and newly described condition. We speculate that repetitive, chronic, needle trauma in susceptible persons can induce massive dystrophic calcinosis cutis.

Aged↗
PubMed1996

Leptospira interrogans serovar grippotyphosa infection in dogs.

Leptospirosis attributed to infection with serovar grippotyphosa was diagnosed in 11 dogs. In naturally and experimentally infected dogs, a stereotypic serologic response to infection with Leptospira serovar grippotyphosa was detected. Although the highest serum antibody titers developed against serovar grippotyphosa, most dogs also had lower titers against serovars bratislava and pomona. Acute renal failure was evident in 10 dogs. One dog died prior to initiation of treatment; the remaining 10 dogs were treated with antibiotics and fluids. Two dogs were euthanatized, 2 dogs recovered without clinical or biochemical evidence of residual renal dysfunction, and 6 dogs recovered but had varying degrees of renal insufficiency. Hepatic involvement appeared to be a minor component of the disease in these dogs. Our results indicate that Leptospira serovar grippotyphosa infection is an important problem in dogs and should be considered when evaluating a dog with renal failure.

Acute Kidney Injury↗