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Biomedical subjects

R G Jenkins

Publications and source records attributed to R G Jenkins.

At least 19 recordsLinked to original sources
PubMed2001

Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice.

Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen production. Its synthesis by fibroblasts is induced by profibrotic mediators including transforming growth factor (TGF)-beta(1). However, in patients with pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production, and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF-beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung. Functionally, this correlates with a loss of the anti-proliferative response to TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis.

Bleomycin↗
PubMed2000

An integrin-targeted non-viral vector for pulmonary gene therapy.

Gene therapy offers potential for the treatment of severe respiratory diseases. However, the vectors which are currently available have drawbacks limiting their therapeutic application. Here we report on an integrin-targeted, non-viral gene delivery system for pulmonary gene transfer. We demonstrate that this vector can deliver the lacZ reporter gene to the lung, transfecting bronchial epithelium and parenchymal cells with similar efficiency to an adenoviral vector and with greater efficiency than a cationic liposome. In addition, vector administration can be repeated leading to further gene expression without inducing inflammation. The advantages of this novel gene delivery system provide considerable potential for targeted gene therapy in vivo. Gene Therapy (2000) 7, 393-400.

Animals↗
PubMed2000

Antibiotics and return visits for respiratory illness: a comparison of pooled versus hierarchical statistical methods.

BACKGROUND: Antibiotic prescribing for respiratory illness has been associated with small reductions in return visits in an analysis of a large practice-based network. In this study, we apply hierarchical analytical methods that account for the clustering of patients by practices to identify whether antibiotic prescribing by primary care physicians reduces subsequent visits for 6 acute respiratory illnesses-upper respiratory infection, pharyngitis, bronchitis, otitis media, sinusitis, and cough. METHODS: The study data came from 318 family physicians and internists in 45 practices in the Practice Partner Research Network from January 1995 through December 1996, with 255,564 active patients. Patients treated with antibiotics were compared with those who were not on the frequency of revisit within the next 14 days. A simple pooling model and 3 hierarchical statistical models (fixed-effects, random-effects, and Bayesian) were used to compare the odds-ratios for return visits. RESULTS: Statistically significant results were found only for bronchitis and sinusitis by the hierarchical models, but the simple pooling model produced statistically significant results for all study conditions. CONCLUSION: We conclude that antibiotics may reduce return visits for patients with bronchitis and sinusitis, but not for patients with other respiratory illness (upper respiratory infection, pharyngitis, otitis media, or cough). Studies of large clinical databases should use methods of analysis that account for the grouping of patients by practice to avoid false positive associations (type I errors.)

Academic Medical Centers↗
PubMed2000

Preventive services in the primary care practices of the Practice Partner Research Network.

Despite the emphasis of primary care on preventive services over the past decade, and the reminder systems that are available to promote the provision of these services, many patients still do not receive needed services. This study describes the preventive services that the primary care practices of the Practice Partner Research Network (PPRNet) monitors, and documents adherence to them. Preventive services monitored in PPRNet practices and the levels of adherence to them vary by practice and service. The lower-than-desired levels of adherence offer opportunities for improvement interventions.

Data Collection↗
PubMed1999

Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK.

A resorcylic acid lactone, L-783,277, isolated from a Phoma sp. (ATCC 74403) which came from the fruitbody of Helvella acetabulum, is a potent and specific inhibitor of MEK (Map kinase kinase). L-783,277 inhibits MEK with an IC50 value of 4 nM. It weakly inhibits Lck and is inactive against Raf, PKA and PKC. L-783,277 is an irreversible inhibitor of MEK and is competitive with respect to ATP. L-783,290, the trans-isomer of L-783,277, was isolated from the same culture and evaluated together with several semi-synthetic resorcylic acid lactone analogs. A preliminary structure-activity relationship is presented. Several independent cell-based assays have been carried out to study the biological activities of these resorcylic acid lactone compounds and a brief result summary from these studies is presented.

Adenosine Triphosphate↗
PubMed1999

Quality of care for chronic illness in primary care: opportunity for improvement in process and outcome measures.

OBJECTIVE: To describe adherence to a number of quality indicators and clinical outcomes for asthma, diabetes mellitus, hypertension, coronary heart disease, atrial fibrillation, and cerebrovascular disease in the primary care practices of the Practice Partner Research Network (PPRNet). STUDY DESIGN: Cross-sectional epidemiologic design. PATIENTS AND METHODS: PPRNet is a national research network of ambulatory, mostly primary care practices that use the Practice Partner Patient Records electronic medical records. Participating practices send anonymous clinical data on patients to the PPRNet data center monthly. Standard database management and statistical software are used to compile practice reports. These reports include measures of adherence to process and outcome measures for chronic illnesses, the subject of this report. RESULTS: Forty-eight PPRNet practices provided data for the first quarter of 1998. A total of 336,401 patients were active in these practices during this quarter. At least 2000 active patients had each of the conditions studied. Wide variation in guideline adherence among PPRNet practices was present for each of the performance measures. Better performance was present for physical examination measures and laboratory monitoring than for treatment interventions. Overall performance was excellent for blood pressure monitoring, poor for lipid monitoring in patients with CHD, and intermediate for glycosylated hemoglobin monitoring in patients with diabetes mellitus. CONCLUSION: The findings of this study are comparable to others in documenting that most clinical practice guidelines for chronic illness are not followed for a majority of patients and that large majorities do not reach desired clinical outcomes.

Asthma↗
PubMed1999

Treatment of recurrent otitis media after a previous treatment failure. Which antibiotics work best?

BACKGROUND: Recurrent infection after an episode of otitis media is common in pediatric patients. If a patient experienced primary treatment failure in a preceding episode, physicians often feel pressured to prescribe a broad-spectrum, second-line agent for the next episode rather than a first-line drug. The purpose of our study was to determine whether using a second-line drug resulted in fewer treatment failures in a recurrent otitis episode following an episode of apparent resistance. METHODS: The Practice Partner Research Network database, a national research network of practices that use the same electronic medical record, was reviewed to identify all primary episodes of otitis media over a 2-year period (N = 7807). From this, 1416 pediatric patients with presumed treatment failures were identified. The subset of those with a second otitis media episode more than 90 days after the index episode (N = 343) was selected for study. Of this group, 236 (69%) received first-line antibiotics (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) and the remaining 107 received a broader-spectrum, second-line antibiotic. The primary outcome was the need for an additional antibiotic for otitis media within the next 45 days. RESULTS: Patients receiving first- and second-line antibiotics did not differ in sex or age. However, those receiving second-line antibiotics had a shorter duration between episodes (231 vs 280 days, P = .007). Failure rates for first- and second-line antibiotics in recurrent episodes were not significantly different (13% vs 19%, P = .20). Because the duration between episodes could have affected failure rates, we stratified the time between episodes into short, intermediate, and long duration. Second-line antibiotics were not superior to first-line drugs in any stratum. CONCLUSIONS: For a new otitis media episode in a patient with a previous treatment failure, first-line drugs (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) are just as effective as broader-spectrum, more expensive, second-line antibiotics.

Acute Disease↗
PubMed1998

Clavaric acid: a triterpenoid inhibitor of farnesyl-protein transferase from Clavariadelphus truncatus.

Farnesyl-protein transferase (FPTase) catalyses the specific transfer of farnesyl to Ras-peptides that is essential for oncogenic activity in oncogene-mediated tumors. Specific inhibition of FPTase activity has been shown to reduce tumor development in nude mice challenged with oncogenic forms of ras, thereby establishing FPTase as a viable therapeutic target. Our continued efforts to discover inhibitors of FPTase has led to the discovery of a triterpenoidal inhibitor, clavaric acid (1). This compound inhibits rHFPTase with an IC50 value of 1.3 microM. Structure elucidation, structure modifications, and biological activity of clavaric acid are herein described.

Alkyl and Aryl Transferases↗
PubMed1998

Electronic medical records as tools for quality improvement in ambulatory practice: theory and a case study.

Information management is critical in today's health care environment. Traditional paper-based medical records are inadequate information management tools. Electronic medical records (EMRs) overcome many problems with paper records and are ideally suited to help physicians increase productivity and improve the quality of care they provide. The Department of Family Medicine at the Medical University of South Carolina uses the Practice Partner Patient Record EMR system. Department members have developed a quality improvement model based on this EMR system. The model has been used to improve care for acute bronchitis, diabetes mellitus, tobacco abuse, asthma, and postmenopausal osteoporosis.

Academic Medical Centers↗
PubMed1997

Oreganic acid, a potent inhibitor of ras farnesyl-protein transferase.

A sulfated tricarboxylic acid fungal metabolite is an inhibitor of human farnesyl-protein transferase (FPTase). The compound, designated as oreganic acid, has a molecular weight of 494, an empirical formula of C22H38O10S and inhibits FPTase with an IC50 value of 14 nM. Oreganic acid is a selective inhibitor of FPTase because it does not inhibit human geranylgeranyl-protein transferase type I (GGPTase-I). It is not a time-dependent inhibitor, reversibly inhibits FPTase, is competitive with respect to farnesyl diphosphate and non-competitive with respect to the Ras acceptor peptide. The structure of oreganic acid resembles that of farnesyl diphosphate and most likely inhibits FPTase by mimicking farnesyl diphosphate at the active site of the enzyme.

Alkyl and Aryl Transferases↗
PubMed1997

The computer-based patient record as a CQI tool in a family medicine center.

BACKGROUND: In 1994 the Department of Family Medicine (DFM) at the Medical University of South Carolina (MUSC) developed an innovative infrastructure for continuous quality improvement (CQI) which capitalized on its existing computer-based patient record (CPR) system. CQI PROGRAM: The CPR is a key element in all components of the DFM patient care CQI activities. Computerized record reviews, online queries, and special reports provide the background information needed to establish CQI projects and, in some cases, diagnose the cause. Any data entered into the CPR, including progress notes text, is searchable for use by the quality improvement teams. The most compelling aspect of DFM's CPR-based CQI system is the use of quality control charts that are regularly generated by the research division from CPR data. These charts allow the CQI teams to determine whether any changes in the process measurements are due to chance causes or are caused by specific interventions introduced to improve the process. ONGOING IMPROVEMENT PROJECTS: Four ongoing improvement projects that rely on CPR data and use electronically created control charts are discussed--optimizing the treatment of acute bronchitis, improving adherence to practice guidelines for patients with adult onset diabetes mellitus, improving the recognition and treatment of tobacco abuse, and improving blood pressure control in patients with hypertension. Each improvement project has a unique set of goals and objectives, against which the project's success is measured. CONCLUSION: A CPR system can be used to provide fast, organized access to large amounts of patient information to support structured quality improvement activities.

Academic Medical Centers↗
PubMed1995

Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma species.

Three new diphenyl ethers, barceloneic acids A, B, and barceloneic lactone [1, 2, and 3, respectively] were isolated from a fermentation extract of a fungus of the genus Phoma. The structures of compounds 1-3 were determined by a combination of spectroscopic and single-crystal X-ray diffraction methods. The effect of these compounds on the inhibition of farnesyl-protein transferase (FPTase) was evaluated and results are presented. Barceloneic acid A [1] is a novel and modest inhibitor of FPTase with an IC50 value of 40 microM.

Alkyl and Aryl Transferases↗
PubMed1995

Implementation and evaluation of a computer-based preventive services system.

BACKGROUND AND OBJECTIVES: Insufficient attention has been paid to the role that modern information systems can play in improving the delivery of and education about preventive services in family medicine training and practice sites. From September 1990-September 1993, the Department of Family Medicine at the Medical University of South Carolina conducted a demonstration project designed to develop, implement, and evaluate a comprehensive, computer-based preventive services delivery and educational system, based on the recommendations in the US Preventive Services Task Force (USPSTF) Report. METHODS: A computer-based patient record (CPR) system was implemented. The system had sophisticated preventive services tracking and reminder, physician, and patient education features. Twenty-nine basic USPSTF recommendations were incorporated in the system. An extensive physician education series was also implemented. A multi-method evaluation system, including patient exit surveys, physician interviews, and practice audits was used to evaluate and design improvements to the CPR and education systems. RESULTS: Although the system initially had no effect on patient perceptions about the frequency of preventive services delivery, there was reasonable concordance between patient desires and physician behavior for the discussion of preventive services (Kappa = .5 to .6). Physician acceptance of the system was good--in 1992, 30% of physicians used the preventive services reminders in most of their patient visits, and in 1993, 88% of physicians reported more frequent use. Practice audits from February 1992-July 1993 showed increased adherence with all seven counseling services, 10 of 15 screening services, and one of five immunization services. CONCLUSIONS: A CPR-based preventive services system coupled with an adaptable physician education about and delivery of preventive services. an ideal solution to improving the education about and delivery of preventive services.

Adolescent↗
PubMed1995

Family practice educators' perceptions of computer-based patient records.

BACKGROUND: Despite the National Institute of Medicine's endorsement of computer-based patient records (CPRs), the majority of family practice residency programs continue to use paper records. This study examined the perceptions of family medicine educators about CPRs to understand their limited use of computerized patient record systems. METHODS: A survey was mailed to the directors of 247 family practice residency programs; 199 were completed and returned (response rate 81%). Respondents were asked to identify their concerns about CPRs, what they perceived as the advantages and disadvantages of CPRs compared with paper records, and the likelihood that their program will implement a CPR within the next year and within the next 5 years. RESULTS: The perceived benefits of CPR were greater efficiency, accuracy, and quality in patient care. However, many respondents were concerned about cost, mechanical breakdowns, conversion hardships, training needs, and physicians' attitudes. Despite these objections, the majority of respondents reported it is ¿somewhat¿ or ¿very¿ likely that their program will implement a CPR system within the next 5 years. CONCLUSIONS: Although the surveyed family medicine educators believed that CPRs offer significant benefits, they also perceived several disadvantages of converting from paper to computer-based patient records. Widespread use of CPRs among family practice programs in the near future depends on the extent to which vendors and others heighten awareness and knowledge about the benefits of CPRs and address concerns about cost, mechanical breakdowns, and transition difficulties.

Attitude of Health Personnel↗
PubMed1994

Improving a preventive services reminder system using feedback from focus groups.

OBJECTIVE: To improve the computer-generated preventive services patient reminder letter used by a department of family medicine at a medical university in South Carolina. DESIGN: A qualitative method chosen because of its demonstrated efficacy in generating in-depth attitude and opinion data was used for 12 focus groups (111 participants) in which participants were asked to evaluate the reminder letter and other preventive services reminder materials. Information from these groups was used to design a revised patient reminder system that was tested in six additional focus groups (50 participants). SETTING: University-based family medicine center. PARTICIPANTS: Adults 19 years of age or older of whom approximately one half were selected from a random sample of family medicine center patients and the remainder from volunteers recruited from the general community by newspaper advertisement. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Participants' perceptions and attitudes about the reminder letter and other materials as well as suggestions for improving the preventive services reminder system. RESULTS: The revised patient reminder materials resulted in a warmer, more personal letter sent to patients at the time of their birthdays in an envelope containing a prevention message. A leaflet describing the rationale for preventive services and answering common questions about prevention and a booklet describing the preventive services available at the family medicine center were also developed. CONCLUSION: This study illustrated the benefits of incorporating patients' perspectives in the design of preventive services reminders.

Adult↗
PubMed1993

Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protein transferase.

Chaetomellic acids A and B, isolated from Chaetomella acutiseta, are specific inhibitors of farnesyl-protein transferase that do not inhibit geranylgeranyl transferase type 1 or squalene synthase. Chaetomellic acids A and B are reversible inhibitors, resemble farnesyl diphosphate and probably inhibit FPTase by substituting for farnesyl diphosphate. Chaetomellic acid production appears to be widespread within the genus Chaetomella.

Alkyl and Aryl Transferases↗