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Biomedical subjects

Michael J Green

Publications and source records attributed to Michael J Green.

At least 19 recordsLinked to original sources
PubMed2006

Response to intramuscular methyl prednisolone in inflammatory hand pain: evidence for a targeted clinical, ultrasonographic and therapeutic approach.

BACKGROUND: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. OBJECTIVE: To assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. METHODS: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. RESULTS: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p < or = 0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. CONCLUSIONS: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.

Adult↗
PubMed2006

Evaluation of antitumor properties of novel saframycin analogs in vitro and in vivo.

Novel analogs of (-)-saframycin A are described. The analogs are shown to be potent inhibitors of the in vitro growth of several tumor cells in a broad panel and promising as leads for further optimization. The first in vivo studies in a solid tumor model (HCT-116) reveal potent antitumor activity with associated toxicity of daily administration.

Animals↗
PubMed2006

Potent 4-amino-5-azaindole factor VIIa inhibitors.

The 4-amino-5-azaindole as an amidino-benzimidazole replacement is described. A series of potent and selective analogs were discovered and showed desirable ex vivo efficacy as measured by PT.

Factor VIIa↗
PubMed2006

Structure-guided design of peptide-based tryptase inhibitors.

Improved peptide-based inhibitors of human beta tryptase were discovered using information gleaned from tripeptide library screening and structure-guided design methods, including fragment screening. Our efforts sought to improve this class of inhibitors by replacing the traditional Lys or Arg P1 element. The optimized compounds display low nanomolar potency against the mast cell target and several hundred-fold selectivity with respect to serine protease off targets. Thus, replacement of Lys/Arg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in target affinity.

Crystallography, X-Ray↗
PubMed2006

Factor VIIa inhibitors: a prodrug strategy to improve oral bioavailability.

We have developed a series of potent and selective factor VIIa inhibitors based on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid scaffold. These amidine-containing compounds have low oral bioavailability. Herein, we describe our efforts to improve the oral bioavailability of the parent amidine via a prodrug strategy where the amidine basicity and polarity were reduced with either an alkoxy-amidine or a carbamate prodrug.

Administration, Oral↗
PubMed2006

Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.

Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.

Animals↗
PubMed2005

Early oligoarthritis.

Oligoarthritis is a common condition, with a variable outcome, affecting a predominantly young population; when treated conventionally, oligoarthritis has a high morbidity. The variability of outcome has limited the development of studies evaluating therapies such as disease-modifying antirheumatic drugs in recent onset disease. Oligoarthritis is an important disease that warrants much greater study.

Arthritis↗
PubMed2005

Use of an educational computer program before genetic counseling for breast cancer susceptibility: effects on duration and content of counseling sessions.

PURPOSE: Patients seeking genetic testing for inherited breast cancer risk are typically educated by genetic counselors; however, the growing demand for cancer genetic testing will likely exceed the availability of counselors trained in this area. We compared the effectiveness of counseling alone versus counseling preceded by use of a computer-based decision aid among women referred to genetic counseling for a family or personal history of breast cancer. METHODS: We developed and evaluated an interactive computer program that educates women about breast cancer, heredity, and genetic testing. Between May 2000 and September 2002, women at six study sites were randomized into either: Counselor Group (n = 105), who received standard genetic counseling, or Computer Group (n = 106), who used the interactive computer program before counseling. Clients and counselors both evaluated the effectiveness of counseling sessions, and counselors completed additional measures for the Computer Group. Counselors also recorded the duration of each session. RESULTS: Baseline characteristics did not differ significantly between groups. Participants and counselors both rated the counseling sessions as highly effective, whether or not the sessions were preceded by computer use. Computer use resulted in significantly shorter counseling sessions among women at low risk for carrying BRCA1/2 mutations. In approximately half of the sessions preceded by clients' computer use, counselors indicated that clients' use of the computer program affected the way they used the time, shifting the focus away from basic education toward personal risk and decision-making. CONCLUSION: This study shows that the interactive computer program "Breast Cancer Risk and Genetic Testing" is a valuable adjunct to genetic counseling. Its use before counseling can shorten counseling sessions and allow counselors to focus more on the clients' individual risks and specific psychological concerns. As the demand for counseling services increases, a program such as this can play a valuable role in enhancing counseling efficiency.

Breast Neoplasms↗
PubMed2004

Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial.

CONTEXT: As the availability of and demand for genetic testing for hereditary cancers increases in primary care and other clinical settings, alternative or adjunct educational methods to traditional genetic counseling will be needed. OBJECTIVE: To compare the effectiveness of a computer-based decision aid with standard genetic counseling for educating women about BRCA1 and BRCA2 genetic testing. DESIGN: Randomized controlled trial conducted from May 2000 to September 2002. SETTING AND PARTICIPANTS: Outpatient clinics offering cancer genetic counseling at 6 US medical centers enrolled 211 women with personal or family histories of breast cancer. INTERVENTIONS: Standard one-on-one genetic counseling (n = 105) or education by a computer program followed by genetic counseling (n = 106). MAIN OUTCOME MEASURES: Participants' knowledge, risk perception, intention to undergo genetic testing, decisional conflict, satisfaction with decision, anxiety, and satisfaction with the intervention. Counselor group measures were administered at baseline and after counseling. Computer group measures were administered at baseline, after computer use, and after counseling. Testing decisions were assessed at 1 and 6 months. Outcomes were analyzed by high vs low risk of carrying a BRCA1 or BRCA2 mutation. RESULTS: Both groups had comparable demographics, prior computer experience, medical literacy, and baseline knowledge of breast cancer and genetic testing, and both counseling and computer use were rated highly. Knowledge scores increased in both groups (P<.001) regardless of risk status, and change in knowledge was greater in the computer group compared with the counselor group (P =.03) among women at low risk of carrying a mutation. Perception of absolute risk of breast cancer decreased significantly after either intervention among all participants. Intention to undergo testing decreased significantly after either intervention among low-risk but not high-risk women. The counselor group had lower mean scores on a decisional conflict scale (P =.04) and, in low-risk women, higher mean scores on a satisfaction-with-decision scale (P =.001). Mean state anxiety scores were reduced by counseling but were within normal ranges for both groups at baseline and after either intervention, regardless of risk status. CONCLUSIONS: An interactive computer program was more effective than standard genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk of carrying a BRCA1 or BRCA2 mutation. However, genetic counseling was more effective than the computer at reducing women's anxiety and facilitating more accurate risk perceptions. These results suggest that this computer program has the potential to stand alone as an educational intervention for low-risk women but should be used as a supplement to genetic counseling for those at high risk.

Adult↗
PubMed2004

Jading in the pediatric intensive care unit: Implications for healthcare providers of medically complex children.

OBJECTIVE: To discuss the phenomenon of jading within the context of the pediatric intensive care unit. DESIGN: Drawing from their experience, the authors describe and then discuss a clinical scenario readily recognizable by pediatric intensive care unit practitioners: a child whose care requires the expenditure of a large amount of energy and resources, provides seemingly little reward, and leads to jading of the PICU staff. CONCLUSION: Jading describes a process of exhaustion whereby apathy, cynicism, and callousness replace the drive to be responsive, to make a difference, and to care. The issue of jading has become an increasing area of concern in the pediatric intensive care unit, due in part to recurring, prolonged admissions, combined with the perception, at times, that continued medical care is fruitless. With a better understanding of the phenomenon of jading, and by reconsidering their own responses, pediatric intensive care unit practitioners can avoid becoming jaded.

Burnout, Professional↗
PubMed2003

"Genetic exceptionalism" in medicine: clarifying the differences between genetic and nongenetic tests.

Predictive genetic tests are now available for assessing susceptibility to a variety of conditions, including breast and colon cancer, hemochromatosis, and Alzheimer and Huntington disease. Much controversy surrounds the application of these tests, stemming from their similarities to and differences from other tests commonly used in asymptomatic persons. Some have argued that genetic tests are unique and therefore justify special consideration with regard to informed consent and privacy. This paper examines the arguments for such "genetic exceptionalism" and concludes that no clear, significant distinctions between genetic and nongenetic tests justify a different approach to testing by clinicians. Nevertheless, with many genetic tests, the results may cause stigmatization, family discord, and psychological distress. Regardless of whether a test is genetic, when this combination of characteristics is present and when health care providers are not specifically trained to interpret results, testing should be performed with particular caution and the highest standards of informed consent and privacy protection should be applied.

Ethics, Medical↗
PubMed2003

Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis.

OBJECTIVE: To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis (RA). METHODS: Forty patients with early, untreated RA underwent gadolinium-enhanced magnetic resonance imaging (MRI) of the second through fifth metacarpophalangeal joints of the dominant hand at presentation, 3 months, and 12 months. In the first phase (0-3 months), patients were randomized to receive either methotrexate alone (MTX) or MTX and intraarticular corticosteroids (MTX + IAST) into all joints with clinically active RA. The MTX-alone group received no further corticosteroids until the second phase (3-12 months), when both groups received standard therapy. RESULTS: In the first phase, MTX + IAST reduced synovitis scores more than MTX alone. There were significantly fewer joints with new erosions on MRI in the former group compared with the latter. During the second phase, the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI. In both phases, there was a close correlation between the degree of synovitis and the number of new erosions, with the area under the curve for MRI synovitis the only significant predictor of bone damage progression. In individual joints, there was a threshold effect on new bone damage related to the level of synovitis; no erosions occurred in joints without synovitis. CONCLUSION: In early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in its absence. In the treatment of patients with RA, outcome measures and therapies should focus on synovitis.

Adrenal Cortex Hormones↗
PubMed2003

Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol.

OBJECTIVE: Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients. METHODS: One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step-up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease-modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months. RESULTS: Seventy-eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis. CONCLUSION: Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.

Adolescent↗