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Biomedical subjects

D C Morris

Publications and source records attributed to D C Morris.

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

The changing healthcare market and how it has influenced the treatment of cardiovascular disease--Part 1.

The dramatic transformations taking place in the healthcare environment have created a new paradigm for healthcare and pose far-reaching changes for cardiovascular care. This 2-part paper reviews these changes and discusses the major implications for cardiovascular specialists, based on literature reviews and summaries of legislative initiatives. The new healthcare paradigm focuses on a continuum of care, wellness maintenance and promotion, accountability for the healthcare of defined populations, and provider differentiation based on ability to add 'value' to the patient's healthcare outcome. This paradigm will become 'standard operating procedure' in the cardiovascular market. As a result, major areas of change in the cardiovascular environment include: continuing growth of managed care arrangements, expanding physician and other payment reforms, growing influence of state and private payer initiatives, expanding role of 'centers of excellence,' continuing surplus of physicians, growth in pharmaceuticals and new technologies, and extension of evidence-based guidelines. Practice guidelines, in particular, will become an integral part of medical practice and will represent the standards against which medical practice will be measured. Given the prominent position of cardiovascular disease in healthcare, cardiovascular specialists will remain in the forefront of these developments.

Cardiac Surgical Procedures↗
PubMed1999

The effect of primary care gatekeepers on the management of patients with chest pain.

OBJECTIVE: To determine whether patients with chest pain referred to a cardiologist from a gatekeeper managed care organization differ from those referred from an open-access managed care organization. STUDY DESIGN: Retrospective study using clinical and claims data from a cardiac network database. PATIENTS AND METHODS: We reviewed data from 1414 patients with chest pain or angina who were referred to a cardiologist between January 1, 1995, and June 30, 1996. We examined baseline clinical characteristics and subsequent physician practice patterns for these patients, who were referred from either a primary care gatekeeper model (n = 490) or an open-access model (n = 924). RESULTS: Although twice as many open-access patients were referred to a cardiologist, there were no differences in patient demographics or clinical characteristics at the time of referral. Cardiologists ordered similar diagnostic tests for patients from both types of managed care plans, and gatekeeper patients did not have a higher rate of abnormal tests. Rates of cardiac catheterization, coronary angioplasty, myocardial infarction, and hospitalization were similar in both groups. A significantly higher percentage of gatekeeper patients received a cardiac catheterization on the day of referral (7% versus 1%; P = .05). Open-access patients were significantly more likely to continue to be seen by a cardiologist (44% versus 28%; P < .01). Cardiology professional charges per patient were lower among gatekeeper patients ($972 +/- 1398 versus $1187 +/- 1897; P = .06), and total cardiology professional charges were significantly lower for the gatekeeper group because of the smaller number of patients seen. CONCLUSIONS: The type of cardiology services provided to patients with chest pain was not affected by the primary care administrative structure of the managed care organization, but the higher volume of patient referrals from the open-access plan may be an important consideration for cardiology practices participating in capitated contracts. The lower volume of referrals and coordination of care suggest potential cost advantages for the gatekeeper model.

Adult↗
PubMed1998

DNA bending is induced by binding of the peroxisome proliferator-activated receptor gamma 2 heterodimer to its response element in the murine lipoprotein lipase promoter.

The peroxisome proliferator activated receptor gamma 2 (PPAR gamma 2) is a critical transcriptional regulator of adipogenesis. Lipoprotein lipase is one of the earliest genes induced following exposure of pre-adipocytes to PPAR gamma 2 ligands such as the thiazolidinediones. A unique PPAR gamma 2 DNA recognition element was mapped to the region between -171 to -149 bp of the murine LPL promoter, based on transfection analysis of deletion constructs and gel retention assays using bacterially expressed, affinity purified recombinant proteins. Circular permutation analysis determined that binding of the PPAR gamma 2/retinoic acid X receptor (RXR) heterodimer to its LPL promoter recognition element induced DNA bending at an angle of approximately 46 degrees. Parallel studies using an optimal PPAR recognition element obtained a comparable bending angle of 56 degrees. This is the first demonstration that binding of a PPAR protein to its recognition element causes a distortion of the DNA configuration. It indicates that PPAR gamma 2 utilizes a common mechanism shared by other nuclear hormone receptor proteins reported to induce bending at their DNA binding sites.

Animals↗
PubMed1998

Usefulness of the substitution of nonangiographic end points (death, acute myocardial infarction, coronary bypass and/or repeat angioplasty) for follow-up coronary angiography in evaluating the success of coronary angioplasty in patients with angina pectoris.

Historically, restenosis after coronary angioplasty has been assessed angiographically at about 6 months. The desirability of avoiding routine follow-up angiography as well as the recognition that angiographic and clinical assessments are not necessarily the same has prompted greater interest in following patients clinically after angioplasty. Clinical restenosis has been defined as the composite of death, myocardial infarction, coronary surgery, or additional angioplasty within 6 months of the index procedure. Clinical restenosis was observed in 2,340 of 11,473 patients (20.4%). The mortality at 6 months was only 1%. Although there were somewhat more acute myocardial infarctions and coronary surgical procedures, the most frequent event was additional angioplasty. Angiographic restenosis was noted in 30% of patients without clinical restenosis and in 87% of patients with clinical restenosis (p < 0.0001). Patients with clinical restenosis were less likely to be women, had more systemic hypertension, diabetes mellitus, more severe angina originally, fewer prior myocardial infarctions, more multivessel and left anterior descending artery disease, more multisite procedures, more branch site procedures, and longer and tighter stenoses both before and after the procedure. The year of the procedure did not correlate with restenosis. Clinical restenosis is less common than angiographic restenosis and the most common event is additional angioplasty. Although clinical restenosis is rarely fatal, it does result in inconvenience and additional resource consumption.

Angina Pectoris↗
PubMed1998

RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in rat bone and growth plate cartilage.

Using differential display polymerase chain reaction, we cloned a novel cDNA named RoBo-1 from rat tibia. RoBo-1 is abundantly expressed in bone, including the hypertrophic chondrocytes of the growth plate where cartilage is remodeled into bone. RoBo-1 mRNA expression increased in response to two modulators of bone metabolism, estradiol and intermittent mechanical loading, suggesting a role in bone homeostasis. The 1.6-kilobase cDNA encodes a 240-amino acid protein with a cysteine spacing pattern, suggesting that RoBo-1 is a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family. Furthermore, the C-terminal contains a glycosyl-phosphatidylinositol attachment site, suggesting that it is a cell surface protein similar to other mammalian members of this family. The strongest homology of RoBo-1 is to the snake serum-derived phospholipase A2 inhibitors, which uniquely contain two of the cysteine domains but are secreted proteins. Interestingly, RoBo-1 is likely the first membrane-anchored member of this family containing two cysteine domains. Thus, the tissue specificity, responsiveness to bone protective mediators, along with its relationship to the multifunctional urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family suggests that RoBo-1 may play a novel role in the growth or remodeling of bone.

Amino Acid Sequence↗
PubMed1998

Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease.

OBJECTIVES: This study sought to compare the outcome of percutaneous transluminal coronary angioplasty (PTCA) (n = 834) and coronary artery bypass graft surgery (CABG) (n = 1805) in diabetic patients with multivessel coronary disease from an observational database. BACKGROUND: There is concern about selection of revascularization in diabetic patients with multivessel coronary artery disease. METHODS: Data were collected prospectively and entered into a computerized database. Follow-up was by letter or telephone or additional events resulting in readmission. RESULTS: After CABG there were more in-hospital deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q wave myocardial infarctions than after PTCA. Five- and 10-year survival rates were 78% and 45% after PTCA and 76% and 48% after CABG, respectively (p = 0.47). At 5 and 10 years, insulin-requiring patients had lower survival rates of 72% and 31% after PTCA and 70% and 48% after CABG, respectively (p = 0.54). Multivariate correlates of long-term mortality were older age, low left ventricular ejection fraction, heart failure and hypertension. In the total group, insulin requirement was a correlate of long-term mortality. For the total group, choice of therapy had a multivariate hazard ratio close to 1. In the insulin-requiring subgroup, the multivariate hazard ratio was 1.35 (95% confidence interval 1.01 to 1.79) for PTCA versus CABG. Corrected for baseline differences, 5- and 10-year survival rates were 68% and 36% after PTCA and 75% and 47% after CABG, respectively, in the insulin-requiring subgroup. Nonfatal events were more common after PTCA, especially additional revascularization. CONCLUSIONS: This study reveals a high incidence of events in diabetic patients and raises further questions about angioplasty in insulin-requiring diabetic patients with multivessel disease.

Aged↗
PubMed1998

Emergency department cardiopulmonary bypass in the treatment of human cardiac arrest.

OBJECTIVE: To study the use of emergency department (ED) femoro-femoral cardiopulmonary bypass (CPB) in the resuscitation of medical cardiac arrest patients. DESIGN: Prospective, uncontrolled trial. SETTING: Urban academic ED staffed with board-certified emergency physicians (EPs). PARTICIPANTS: Ten patients with medical cardiac arrest unresponsive to standard therapy. INTERVENTIONS: Femoro-femoral CPB instituted by EPs. RESULTS: The time of cardiac arrest prior to CPB (mean+/-SD) was 32.0+/-13.6 min. The cardiac output while on CPB was 4.09+/-1.03 L/min with an average of 229+/-111 min on bypass. All 10 patients had resumption of spontaneous cardiac activity while on CPB. Seven of these were weaned from CPB with intrinsic spontaneous circulation. Of these, six patients were transferred from the ED to the operating room for cannula removal and vessel repair while the other patient died in the ED soon after discontinuing CPB. Mean survival was 47.8+/-44.7 h in the six patients leaving the ED. Although these patients had successful hemodynamic resuscitation, there were no long-term survivors. CONCLUSION: CPB instituted by EPs is feasible and effective for the hemodynamic resuscitation of cardiac arrest patients unresponsive to advanced cardiac life support therapy. Future efforts need to focus on improving long-term outcome.

Adolescent↗
PubMed1997

Angioplasty or surgery for multivessel coronary artery disease: comparison of eligible registry and randomized patients in the EAST trial and influence of treatment selection on outcomes. Emory Angioplasty versus Surgery Trial Investigators.

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

Aged↗
PubMed1997

Outcome of reoperative coronary bypass surgery versus coronary angioplasty after previous bypass surgery.

BACKGROUND: The immediate and long-term outcomes of reoperative coronary artery bypass surgery (CABG) (n = 1561) and catheter-based coronary intervention (angioplasty) (n = 2613) were compared in patients from Emory University Hospitals who had previous CABG. METHODS AND RESULTS: The surgical and angioplasty procedures and statistical methods were standard. Data were collected prospectively and entered into a computerized database. Followup was by letter, telephone, or additional events resulting in readmission. In the angioplasty group, 2.9% required in-hospital CABG. Hospital mortality was 1.2% after angioplasty versus 6.8% after repeat CABG (P < .0001). Recurrent angina was noted frequently at about 4 years and was more common after angioplasty. One-, 5-, and 10-year mortalities were 11%, 24%, and 49% after CABG versus 6%, 22%, and 38% after angioplasty. Survival corrected for baseline differences did not vary with the choice of procedure. There were more additional procedures after angioplasty. Patients undergoing angioplasty may be divided into those with procedures only in native coronary arteries (n = 1545), only in vein grafts (n = 869), and a mixture (n = 199), with respective 10 year survivals of 66%, 56%, and 65% (P < .0001). CONCLUSIONS: These patients have a high incidence of events both in-hospital and in the long term. Although initial mortality was higher after CABG, after baseline differences were accounted for, there was no difference in the long term. Patients more frequently have additional procedures after angioplasty. Choice of therapy should consider clinical and angiographic suitability and patient preference.

Analysis of Variance↗
PubMed1997

Hemodynamic effects of aortic occlusion during hemorrhagic shock and cardiac arrest.

OBJECTIVE: To determine the hemodynamic consequences of aortic occlusion during controlled hemorrhagic arrest. METHODS: Ten anesthetized, hemodynamically monitored swine were subjected to a 40 mL/kg hemorrhage over 10 minutes, followed by a 5-minute period of apnea. At this time (T15), they were randomized into an UP group (n = 5) in which the thoracic aorta was occluded or a DOWN group (n = 5) in which the aorta was not occluded. Simultaneously, volume resuscitation with shed blood plus 20 mL/kg of normal saline was performed over a 10-minute period. Cardiac massage was performed until return of spontaneous circulation (ROSC), which was defined as a sustained systolic blood pressure > 60 mm Hg. After 30 minutes of occlusion (T45), the aortic occlusion was released. Parameters measured include mixed venous and arterial blood gases, serum lactic acid levels, cardiac index, mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), coronary perfusion pressure (CoPP), and left ventricular stroke work index (LVSWI). Oxygen delivery index (DO2I) was measured using a pulmonary artery catheter, and oxygen consumption index (VO2I) was measured by direct calorimetry (Delta Trac metabolic monitor). RESULTS: Four animals in each group achieved ROSC after 3.0 +/- 1.8 and 2.2 +/- 1.8 minutes in the occluded and nonoccluded groups, respectively. During cardiac compressions and volume resuscitation, the CoPP, MAP, and MPAP were greater in the UP group, although the differences did not achieve statistical significance. After volume resuscitation was complete and during the period of aortic occlusion (T25-T45), the UP group had significantly greater MAP (mm Hg), with a difference of 42.5 +/- 20.75 mm Hg at T25 and 44.7 +/- 19 mm Hg at T35 (p < 0.03). Despite no difference in DO2I, VO2I (mL/min/kg) was significantly lower in the UP group than in the DOWN group, 4.28 +/- 0.48 versus 8.33 +/- 0.85 at T25 (p = 0.0002) and 4.62 +/- 0.9 versus 7.09 +/- 0.72 at T35 (p = 0.0005). After release of aortic occlusion at T45, the UP group had significantly lower CoPP (mm Hg) than the DOWN group (20.5 +/- 17.3 versus 66.5 +/- 28.2 at T45, p = 0.03). LVSWI (g/kg) was also lower in the UP than in the DOWN group (18.6 +/- 8.28 versus 36.5 +/- 10.2 at T60 [p = 0.031 and 23.6 +/- 6.48 versus 48.8 +/- 15.3 at T240 [p = 0.021). After release of the occlusion, there were trends toward increased acidosis and lactic acid levels in the UP group. CONCLUSIONS: Aortic occlusion in this controlled hemorrhagic arrest model does not result in improved salvage but is associated with impaired left ventricular function, systemic oxygen utilization, and coronary perfusion pressure in the postresuscitation period.

Animals↗
PubMed1997

Vasopressin can increase coronary perfusion pressure during human cardiopulmonary resuscitation.

OBJECTIVES: To determine the hemodynamic effect of vasopressin on coronary perfusion pressure (CPP) in prolonged human cardiac arrest. METHODS: A prospective, open-label clinical trial of vasopressin during cardiac resuscitation was performed. Ten patients presenting in cardiac arrest initially received resuscitative measures by emergency physicians according to Advanced Cardiac Life Support (ACLS) guidelines. A central venous catheter for fluid and drug administration and a femoral artery catheter for measurement of CPP (aortic minus right atrial relaxation phase pressures) were placed. When each patient was deemed nonsalvageable, 1.0 mg epinephrine was given and CPP was measured for 5 minutes, followed by a dose of vasopressin (1.0 U/kg). CPP measurements were continued for another 5 minutes. RESULTS: The mean duration of cardiac arrest (out-of-hospital interval plus duration of ED ACLS) was 39.6 +/- 16.5 min. There was no improvement in CPP after 1.0 mg of epinephrine. Vasopressin administration resulted in a significant increase of CPP in 4 of the 10 patients. Patients responding to vasopressin had a mean increase in CPP of 28.2 +/- 16.4 mm Hg (range: 10-51.5), with these peak increases occurring at 15 seconds to 4 minutes after administration. The increases in the vasopressin levels after administration did not differ between the responders and nonresponders. CONCLUSIONS: In this human model of prolonged cardiac arrest, 40% of the patients receiving vasopressin had a significant increase in CPP. This pilot study suggests that investigation of earlier use of vasopressin as a therapeutic alternative in the treatment of cardiac arrest is warranted.

Adult↗
PubMed1997

Dissection of the molecular mechanism of action of GW5638, a novel estrogen receptor ligand, provides insights into the role of estrogen receptor in bone.

The estrogen receptor (ER) mixed agonists tamoxifen and raloxifene have been shown to protect against bone loss in ovariectomized rats. However, the mechanism by which these compounds manifest their activity in bone is unknown. We have used a series of in vitro screens to select for compounds that are mechanistically distinct from tamoxifen and raloxifene in an effort to define the properties of an ER modulator required for bone protection. Using this approach, we identified a novel high affinity ER antagonist, GW5638, which when assayed in vitro functions as an ER antagonist, inhibiting the agonist activity of estrogen, tamoxifen, and raloxifene and reversing the "inverse agonist" activity of the pure antiestrogen ICI182,780. Thus, GW5638 appears to function as an antagonist in these in vitro systems, although in a manner distinct from other known ER modulators. Predictably, therefore, GW5638 alone displays minimal uterotropic activity in ovariectomized rats, but will inhibit the agonist activity of estradiol in this environment. Unexpectedly, however, this compound functions as a full ER agonist in bone and the cardiovascular system. These data suggest that the mechanism by which ER operates in different cells is not identical, and that classical agonist activity is not required for the bone protective activity of ER modulators.

Animals↗
PubMed1997

Fluorescent microtiter screening assay for immunocytochemically reactive antibodies.

We have developed a rapid in situ screening procedure that enables prescreening of hundreds of hybridomas in a 96-well format. The procedure involves fluorescence immunostaining of cells cultured in 96-well plates and the use of a fluorescence plate reader to detect reactive antibodies. Positive immunostaining in individual well, as denoted by elevated readings, is then confirmed by fluorescence microscopy. Using the method described here, we have successfully identified monoclonal antibodies that are specific to the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). This assay is readily applicable for screening hybridomas raised against cell surface or intracellular antigens to aid in the initial identification of antibodies reactive in immunocytochemical procedures.

Amino Acid Sequence↗
PubMed1997

Matrix vesicles in osteomalacic hypophosphatasia bone contain apatite-like mineral crystals.

Hypophosphatasia, a heritable disease characterized by deficient activity of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP), results in rickets and osteomalacia. Although identification of TNSALP gene defects in hypophosphatasia establishes a role of ALP in skeletal mineralization, the precise function remains unclear. The initial site of mineralization (primary mineralization) normally occurs within the lumen of TNSALP-rich matrix vesicles (MVs) of growth cartilage, bone, and dentin. We investigated whether defective calcification in hypophosphatasia is due to a paucity and/or a functional failure of MVs secondary to TNSALP deficiency. Nondecalcified autopsy bone and growth plate cartilage from five patients with perinatal (lethal) hypophosphatasia were studied by nondecalcified light and electron microscopy to assess MV numbers, size, shape, and ultrastructure and whether hypophosphatasia MVs contain apatite-like mineral, as would be the case if these MVs retained their ability to concentrate calcium and phosphate internally despite a paucity of TNSALP in their investing membranes. We found that hypophosphatasia MVs are present in approximately normal numbers and distribution and that they are capable of initiating internal mineralization. There is retarded extravesicular crystal propagation. Thus, in hypophosphatasia the failure of bones to calcify appears to involve a block of the vectorial spread of mineral from initial nuclei within MVs, outwards, into the matrix. We conclude that hypophosphatasia MVs can concentrate calcium and phosphate internally despite a deficiency of TNSALP activity.

Apatites↗
PubMed1996

Activation of the nuclear receptor peroxisome proliferator-activated receptor gamma promotes brown adipocyte differentiation.

Brown adipose tissue (BAT) functions in non-shivering and diet-induced thermogenesis via its capacity for uncoupled mitochondrial respiration. BAT dysfunction in rodents is associated with severe defects in energy homeostasis, resulting in obesity and hyperglycemia. Here, we report that the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), a prostaglandin-activated transcription factor recently implicated as a central regulator of white adipose tissue differentiation, also regulates brown adipocyte function. PPARgamma is abundantly expressed in both embryonic and adult BAT. Treatment of CD-1 rats with the PPARgamma-selective ligand BRL49653, an anti-diabetic drug of the thiazolidinedione class, results in marked increases in the mass of interscapular BAT. In vitro, BRL49653 induces the terminal differentiation of the brown preadipocyte cell line HIB-1B as judged by both changes in cell morphology and expression of uncoupling protein and other adipocyte-specific mRNAs. These data demonstrate that PPARgamma is a key regulatory factor in brown adipocytes and suggest that PPARgamma functions not only in the storage of excess energy in white adipose tissue but also in its dissipation in BAT.

Adipocytes↗
PubMed1996

Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells.

The thiazolidinediones improve insulin sensitivity in animal models and have promise as potent oral antidiabetic agents. Their clinical use has been limited because of the resulting anemia and cardiac hypertrophy. Some compounds of this class have been reported to induce bone marrow fat accumulation in animals, and this effect could account for the observed anemia. We examined the biological mechanism contributing to this phenomenon. The thiazolidinediones BRL49653 and pioglitazone induced adipocyte differentiation in the BMS2 bone marrow stromal cell line in a dose- and time-dependent manner. These actions were further enhanced by the presence of glucocorticoids and other adipogenic agonists. The thiazolidinediones increased the mRNA levels of adipocyte-specific genes, including that of their receptor, the peroxisome proliferator-activated receptor-gamma (PPAR gamma). In contrast, mRNA levels of genes encoding other PPAR family members (PPAR alpha, PPAR delta, or NUC-1) were unchanged or decreased. Thiazolidinedione treatment of primary bone marrow stromal cells elicited a comparable dose-dependent response. Using a polyclonal antibody, PPAR gamma was detected in protein lysates from adipose-rich bone marrow. Thus, thiazolidinedione directly regulates bone marrow stromal cell differentiation; induced PPAR gamma expression may play a key regulatory role in this process.

Adipocytes↗