Amelioration of the premature ageing-like features of Fgf-23 knockout mice by genetically restoring the systemic actions of FGF-23.

Genetic ablation of fibroblast growth factor 23 from mice (Fgf-23(-/-)) results in a short lifespan with numerous abnormal biochemical and morphological features. Such features include kyphosis, hypogonadism and associated infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue calcifications, and generalized atrophy of various tissues. To determine whether these widespread anomalies in Fgf-23(-/-) mice can be ameliorated by genetically restoring the systemic actions of FGF-23, we generated Fgf-23(-/-) mice expressing the human FGF-23 transgene in osteoblasts under the control of the 2.3 kb alpha1(I) collagen promoter (Fgf-23(-/-) /hFGF-23-Tg double mutants). This novel mouse model is completely void of all endogenous Fgf-23 activity, but produces human FGF-23 in bone cells that is subsequently released into the circulation. Our results suggest that lack of Fgf-23 activities results in extensive premature ageing-like features and early mortality of Fgf-23(-/-) mice, while restoring the systemic effects of FGF-23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants. With regard to their serum biochemistry, double mutants reversed the severe hyperphosphataemia, hypercalcaemia, and hypervitaminosis D found in Fgf-23(-/-) littermates; rather, double mutants show hypophosphataemia and normal serum 1,25-dihydroxyvitamin D(3) levels similar to pure FGF-23 Tg mice. These changes were associated with reduced renal expression of NaPi2a and 1 alpha-hydroxylase, compared to Fgf-23(-/-) mice. FGF-23 acts to prevent widespread abnormal features by acting systemically to regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model provides us with an in vivo tool to study the systemic effects of FGF-23 in regulating mineral ion metabolism and preventing multiple abnormal phenotypes without the interference of native Fgf-23.

Normal CK, elevated MB predicts complications in acute coronary syndromes.

The implications of an elevated Creatine kinase (CK)-MB isoenzyme (MB) in suspected acute coronary syndromes, with a normal total CK, is not well established. Despite many guidelines on managing patients with acute coronary ischemia, none indicates strategies for patients with elevated MB and with a normal CK. The outcome consequence of this result is not firmly established. Our objective was to prospectively evaluate outcomes in patients with suspected acute coronary syndromes, normal initial total CK, and increased MB. All Emergency Department patients with suspected acute coronary syndromes and creatinine < 2.0 mg/dL were eligible for study entry. Serial CK and MB fractions were measured on arrival in the Emergency Department, then 8 and 16 h postpresentation. A composite outcome of death, Q-wave myocardial infarction, or revascularization was defined at the index visit and 6 months later. Outcomes were determined by blinded record review and by telephone contact. In the 698 patients entered, the acute composite outcome rate was 25% (175) and 6.3% (44) at 6 months. Acute and 6 month adverse outcome rates were statistically the same for all patients with an elevated MB fraction, regardless of the total CK level. An elevated MB conferred a higher event rate than did a normal MB. We conclude that the adverse event rate for patients with suspected acute coronary syndromes and an elevated MB is the same whether or not the total CK is elevated. These patients should be considered as having had an acute coronary syndrome.

DNA dendrimers localize MyoD mRNA in presomitic tissues of the chick embryo.

MyoD expression is thought to be induced in somites in response to factors released by surrounding tissues; however, reverse transcription-PCR and cell culture analyses indicate that myogenic cells are present in the embryo before somite formation. Fluorescently labeled DNA dendrimers were used to identify MyoD expressing cells in presomitic tissues in vivo. Subpopulations of MyoD positive cells were found in the segmental plate, epiblast, mesoderm, and hypoblast. Directly after laying, the epiblast of the two layered embryo contained approximately 20 MyoD positive cells. These results demonstrate that dendrimers are precise and sensitive reagents for localizing low levels of mRNA in tissue sections and whole embryos, and that cells with myogenic potential are present in the embryo before the initiation of gastrulation.

Comparison of troponin T versus creatine kinase-MB in suspected acute coronary syndromes.

Limitations of creatine kinase-MB (CK-MB) have led to alternative biochemical markers, including troponin T (TnT), to detect myocardial necrosis. Limited data are available regarding the predictive value of this new marker in patients with chest pain of uncertain etiology. Therefore, we prospectively compared CK-MB and TnT in a broad population with suspected acute coronary syndromes, including those admitted to a short-stay chest pain unit. CK-MB, quantitative TnT levels, and a rapid bedside assay were performed at 0, 4, 8, and 16 hours. Adverse events, including infarction, recurrent ischemia, coronary surgery, need for catheterization and/or intervention, stroke, congestive heart failure, or death, were identified by chart review and by follow-up phone call at 6 months. Of 707 patients, 104 were excluded for creatinine >2 mg/dl or incomplete data, leaving a total cohort of 603 patients. Coronary Care Unit admissions were 18%, intermediate care admissions were 14%, telemetry admissions is 21%, and admissions to 24-hour short-stay area were 47%. TnT (at 0.1 ng/ml) and CK-MB were positive in a similar proportion of patients (20.4% and 19.7%, respectively); however, the patients identified by TnT and CK-MB were not identical. In-hospital adverse events occurred in 37.1% with no differences in positive predictive value for the markers (p = NS). If CK-MB and TnT were negative, the early adverse event rate was 27%. No cardiac marker was positive by 16 hours in 54.9% of patients with an adverse event. Six-month follow-up was obtained in 576 of the 603 patients (95.5%). One hundred fifty-five late adverse events occurred in 134 patients (23.3%) at an average of 3.3+/-2.5 months after discharge. If both markers were negative, the late event rate was 20.2% and did not increase in patients with positive CK-MB or TnT >0.2 ng/ml. However, the late event rate was substantially higher (52.9%) in those with intermediate TnT levels of 0.1 to 0.2 ng/ml (p = 0.002). Thus, TnT is a suitable alternative to CK-MB in patients with suspected acute coronary syndromes. The rapid bedside assay is comparable to quantitative TnT and may enable early diagnosis and triage. A negative cardiac marker value (TnT or CK-MB) does not necessarily confer a low risk of complication in patients presenting with acute chest pain to an emergency department.

Prediction of short- and long-term outcomes by troponin T levels in low-risk patients evaluated for acute coronary syndromes.

STUDY OBJECTIVE: Recent reports suggest a short series of cardiac troponin (cTnT) testing effectively identifies patients at risk for cardiac events. However, there are few studies validating this strategy. The purpose of this study was to determine the ability of cTnT levels to predict short- and long-term outcomes in low-risk patients with suspected acute coronary syndromes. METHODS: This prospective longitudinal study was conducted in a 20-bed emergency department observation unit. Patients at low risk for acute coronary ischemia, with a normal creatine kinase-isoenzyme subunit MB (CKMB) index, were admitted to an observation unit for chest pain evaluation. Serum cTnT levels were measured at baseline and at 4, 8, and 16 hours after admission. The main outcome measures were adverse cardiac events (death, acute myocardial infarction, unstable angina, revascularization) during the index visit and within 6 months after discharge. Using manufacturer's recommendations, the cTnT level was considered abnormal if it exceeded 0.2 microg/L. RESULTS: Two hundred sixty-six patients were evaluated. Twenty-one (7.9%) had an adverse event during their index hospitalization. Troponin testing identified only 2 (9.5%) of these patients. Twenty (7.5%) had a cardiac event within 6 months; none were identified by cTnT testing. The sensitivity and specificity were 9.5% and 99.2%, respectively, at the index visit, and 0% and 98.4% at 6 months. The positive and negative predictive values were 50% and 93%, respectively, at the index visit; and 0% and 92% at 6 months. CONCLUSION: Determination of troponin T levels has a low sensitivity and high specificity for predicting outcomes in low-risk patients evaluated for suspected acute coronary syndromes. This study does not support a strategy of relying solely on troponin testing for disposition decisions.

Nursing interventions to decrease bleeding at the femoral access site after percutaneous coronary intervention. SANDBAG Nursing Coordinators. Standards of Angioplasty Nursing Techniques to Diminish Bleeding Around the Groin.

BACKGROUND: This trial is the first prospective, multicenter clinical nursing trial conducted to measure the effect of nursing interventions on bleeding at the femoral access site after percutaneous coronary intervention with or without a potent antiplatelet agent given along with heparin and aspirin. OBJECTIVE: To measure the relationship between nursing interventions and complications at the arterial access site in patients undergoing percutaneous coronary interventions and to recommend a standard of care to minimize bleeding complications. METHODS: In a descriptive, correlational 4010-patient study, nursing care interventions after coronary procedures were measured. Observed standards of care were assessed, and regression techniques were used to evaluate nursing interventions and the effect of the interventions on bleeding at the access site after percutaneous coronary procedures. RESULTS: Several significant correlations between nursing interventions and the occurrences of moderate to severe bleeding at the access site were found; however, most interventions had little effect. The most significant factors in decreasing complications at the access site were early removal of the arterial sheath, the type of pressure mechanism used to achieve arterial hemostasis, staffing allocation, and the person and method used to remove the sheath. CONCLUSION: Many nursing interventions after percutaneous coronary intervention have become routine in the absence of clinical outcome data. Most nursing interventions aimed at decreasing bleeding at the vascular access site increase nursing workload but do not significantly affect bleeding in the groin. These results underscore the importance of continued clinical research studies to validate nursing practice on the basis of patients' outcomes.

Hepatocyte growth factor/scatter factor promotes a switch from E- to N-cadherin in chick embryo epiblast cells.

Epiblast cells downregulate E-cadherin and upregulate N-cadherin as they ingress through the primitive streak and when placed in culture. The factors that promote the alteration in cadherin expression during gastrulation are unknown. The effects of hepatocyte growth factor/scatter factor (HGF/SF) on cadherin expression were tested in cultures of prestreak epiblast cells. HGF/SF decreased the expression of E-cadherin and increased the percentage of cells with N-cadherin and sarcomeric myosin. Cells with N-cadherin but not E-cadherin differentiated into skeletal muscle. HGF/SF also stimulated proliferation and the formation of cellular aggregates. Sensitivity to HGF/SF in vitro depended on the original position of cells within the epiblast. More cells from the lateral epiblast switched cadherins and proliferated in response to HGF/SF than medial epiblast cells. HGF/SF may affect gastrulation by altering cadherin expression, modulating cell adhesion, and stimulating proliferation within the epiblast.

Ability of troponins to predict adverse outcomes in patients with renal insufficiency and suspected acute coronary syndromes: a case-matched study.

OBJECTIVES: The purpose of this study was to investigate the utility of cardiac troponin T and troponin I for predicting outcomes in patients presenting with suspected acute coronary syndromes and renal insufficiency relative to that observed in similar patients without renal disease. BACKGROUND: Cardiac troponin T and troponin I have shown promise as tools for risk stratification of patients with acute coronary syndromes. However, there is uncertainty regarding their cardiac specificity and utility in patients with renal disease. METHODS: We measured troponin T, troponin I and creatine kinase MB in 51 patients presenting with suspected acute coronary syndromes and renal insufficiency and in 102 patients without evidence of renal disease matched for the same peak troponin T or I value, selected from a larger patient cohort. Blood samples were obtained at presentation to an emergency room 4 hours, 8 hours and 16 hours later. The ability of biochemical markers to predict adverse outcomes in both groups including infarction, recurrent ischemia, bypass surgery, heart failure, stroke, death or positive angiography/angioplasty during hospitalization and at six months was assessed by receiver-operator curve analysis. The performance of both troponins was compared between groups. RESULTS: Thirty-five percent of patients in the renal group and 45% of patients in the nonrenal group experienced an adverse initial outcome; over 50% of patients in all groups had experienced an adverse outcome by 6 months, but these differences were not significant. The area under the curve (AUC) for the ROC curve for troponin T as predictor of initial outcomes was significantly lower in the renal group than in the nonrenal group: 0.56+/-0.07 and 0.75+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared with the nonrenal group for troponin T as predictor of six month outcomes: 0.59+/-0.07 and 0.74+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared to the nonrenal group for troponin I as predictor of both initial and six month outcomes: 0.54+/-0.06 vs. 0.71+/-0.07 and 0.53+/- 0.06 vs. 0.65+/-0.07, respectively. The sensitivity of troponin T for both initial and six month adverse outcomes was significantly lower in the renal group than in the nonrenal group at a similar level of specificity (0.87): 0.29 vs. 0.60 and 0.45 vs. 0.56, respectively. Troponin I also exhibited similar differences in sensitivity in the renal group (0.29 vs. 0.50 and 0.33 vs. 0.40, respectively). CONCLUSIONS: The ability of cardiac troponin T and troponin I to predict risk for subsequent adverse outcomes in patients presenting with suspected acute coronary syndromes is reduced in the presence of renal insufficiency.

A guide to successfully recruiting patients for cardiovascular clinical trials.

To maximize enrollment in clinical trials, an efficient mechanism for screening and recruitment is needed. A national referral center for the treatment of heart disease developed a mechanism to maximize patient enrollment in more than 20 clinical trials simultaneously with a cardiac catheterization laboratory. It consists of four primary components: preparation, screening and recruitment, evaluation and problem-solving, and communication. This paper describes these components and presents information that may be useful in the recruitment of patients for clinical trials. It also provides tools that can be adapted and used to screen patients for trial eligibility.

Late myocardial ischemic events after saphenous vein graft intervention--importance of initially "nonsignificant" vein graft lesions.

Patients undergoing percutaneous coronary revascularization (PCR) for narrowed saphenous vein grafts (SVGs) have a high incidence of subsequent cardiac events, but the relative contribution of treated and untreated SVGs, and of native coronary narrowings to late events is uncertain. This study evaluated the role of progression of SVG disease at untreated sites to cardiac events in these patients. All patients with successful PCR of SVG lesions who were enrolled in clinical trials with mandated repeat angiography from 1990 to 1994 were studied. One hundred three patients (age 63 +/- 8 years, 82% men, ejection fraction 54 +/- 12%, graft age 8 +/- 4 years), contributing 1,095 analyzable 15- to 25-mm SVG segments were followed 29 +/- 13 months (4 patients were lost to follow-up). Actuarial event-free (death, myocardial infarction, bypass surgery, or PCR) and overall survival at 12 months were 47 +/- 5% and 94 +/- 2%, respectively. Fifty-six percent of all early (< or = 12 months) events resulted from ischemia from recurrence at initially treated SVG sites, 26% at nontreated SVG sites, and 14% at nontreated native coronary sites. By 36 months, event-free and overall survival were 25 +/- 6% and 86 +/- 4%, respectively. Events occurring > 12 months after initial treatment resulted most frequently from ischemia from progression of narrowing at untreated SVG sites (46%). Ischemic events from initially untreated SVG sites were correlated with initial percent stenosis (initial, 41% to 50%; 45% events, 31% to 40%; 18% events, < or = 30%; 2% events, p <0.001) and reference SVG diameter (p = 0.003). Recurrent ischemic events from initially treated SVG sites were independently correlated with initial percent stenosis (initial > 75%; 43% events, 50% to 75%; 27% events, < 50%; 18% events, p = 0.01), but not with final percent stenosis. The frequent occurrence of events from nontreated 41% to 50% stenoses suggests a need for increased surveillance in patients with these lesions. The low incidence of events from initially treated lesions < 50% suggests that the hypothesis that "nonsignificant" 41% to 50% lesions might best be treated at the time other more severe narrowings are treated should be examined.

Infusion therapy with milrinone in the home care setting for patients who have advanced heart failure.

Advanced heart failure (AHF) is a serious cause of mortality and morbidity in the United States. The treatment of AHF exacts a great financial and manpower toll on the healthcare infrastructure. The quality of life of patients with AHF also is reduced severely. When it is infused at home, Milrinone, which is an intravenous inodilator agent, reduces the number of hospitalizations. Milrinone decreases the overall treatment costs of AHF. Highly skilled home nursing care is required in the treatment of patients. The home care nurse plays a major role in the outcome of a patient with AHF.

Constraint-induced movement therapy for motor recovery after stroke.

A new therapeutic approach to rehabilitation of movement after stroke, termed Constraint-Induced (CI) Movement Therapy, has been derived from basic research with monkeys given somatosensory deafferentation. CI consists of a family of therapies; their common element is that they induce stroke patients to greatly increase the use of a more affected upper extremity for many hours a day over a 10-14 consecutive-day period. These therapies have significantly improved quality of movement and substantially increased amount of use of a more affected extremity in the activities of daily living in the life situation. The purpose of this paper is to describe the protocol used by the investigative team that developed the family of CI therapies and examined them as an effective rehabilitation approach.

Survey of current practice patterns for percutaneous transluminal coronary angioplasty. SANDBAG Nursing Coordinators.

BACKGROUND: The increasing complexity of coronary intervention has led to variations in current patterns of nursing practice for patients undergoing routine percutaneous transluminal coronary angioplasty. In preparation for a large study examining the effects of specific nursing practices on complications at the site of vascular access, we surveyed institutions participating in a randomized phase III trial involving 4010 patients to determine current patterns of practice. OBJECTIVE: The purpose of this study was to determine the current patterns of nursing practice for patients undergoing percutaneous transluminal coronary angioplasty. METHODS: An eight-page questionnaire was completed by 70 hospitals participating in the study titled Integrelin to Manage Platelet Aggregation to Prevent Coronary Thrombosis (IMPACT II). RESULTS: The hospitals participating in this study have an average of 500 beds; 34% of the institutions do 500 to 1000 angioplasty procedures annually. At many sites (39%), heparin is infused for 12 to 18 hours after the intervention, but heparin is not infused at all in 31% of the hospitals studied. At 27% of the hospitals, arterial sheaths are removed 12 to 18 hours after angioplasty, and at 15% of the hospitals, sheaths are removed more than 18 hours after the procedure. Typically after angioplasty (36%), patients are transferred to an ICU, with a nurse-patient ratio of 1:2. Eighty-three percent of the hospitals use CareMAPs or care plans for standardization of care. Most hospitals (83%) require complete bed rest for patients who have had angioplasty, with the affected leg restrained to prevent mobility. Ninety-one percent of the hospitals reported continuing to treat the patient with bed rest for an additional 6 hours after the sheath is removed. CONCLUSION: Comprehensive nursing standards of care based on well-designed clinical trials for patients after angioplasty are not available. In the second phase of our study, we hope to correlate nursing practices with clinical outcome data to improve further the care of patients who have had angioplasty.

The radiology of rheumatoid arthritis.

Rheumatoid arthritis is a connective tissue disorder of unknown etiology that can involve any synovial-lined joint in the body. The most frequently involved joints are the small joints of the hands and feet, the wrists, knees and elbows, and the glenohumeral and acromioclavicular joints. The radiographic hallmarks of rheumatoid arthritis are swelling of the soft tissue, osteoporosis, narrowing of the joint spaces and marginal erosions. The unique combination of osteoporosis, marginal erosions and relatively minimal reactive bone formation help distinguish rheumatoid arthritis from other inflammatory arthritides.

Transvaginal ultrasonography.

Transvaginal ultrasonography is an adjunct to abdominal ultrasonography. It is indicated for investigation of suspected abnormalities of the ovaries, fallopian tubes and uterus, and can provide better resolution than traditional views of this anatomic region. Transvaginal ultrasonography is particularly useful in diagnosing ectopic pregnancy.

Are we promoting true informed consent in cardiovascular clinical trials?

The purpose of this study was to determine variables contributing to patient participation in randomized clinical trials while assessing the potential relationship of these variables to a valid consent process. Two hundred forty-seven patients were administered a questionnaire after they made their decision about participation. Numerous variables were explored for their relationship to patient participation. Of particular significance were the variables of education, perception of having enough time to decide, and the person approaching the patient. Results of this study reveal the need for further evaluation of informed consent as a process, focusing on the areas of patient autonomy and comprehension.

Pulmonary lymphangiomyomatosis.

Lymphangiomyomatosis is a rare disease of unknown etiology characterized by hamartomatous proliferation of smooth muscle in the pulmonary lymphatics, blood vessels and airways. The disease occurs exclusively in women of reproductive age. Although the clinical course and radiographic findings may strongly suggest lymphangiomyomatosis, definitive diagnosis is made by obtaining open-lung biopsy. The clinical course of lymphangiomyomatosis is progressive, leading to pulmonary insufficiency and death within 10 years. Treatment with hormonal manipulation and/or oophorectomy has resulted in temporary improvement or stabilization of the disease process.

Radiographic aspects of pneumothorax.

Pneumothorax is a common medical problem of varied etiology. Because pneumothorax has potentially severe acute consequences, it is important that all physicians know its radiographic appearance. Patient complaints are nonspecific, and physical examination findings are often subtle. The chest radiograph is the principal means of detecting and following a pneumothorax. Radiographic diagnosis on an upright film requires the detection of the visceral pleural line. For radiographs obtained with the patient in the supine position, pneumothorax may be manifested by increased lucency over the upper quadrant of the abdomen, an unusually sharp definition of the anterior diaphragmatic surface or a very wide and deep costophrenic angle.

Intraoral metal adhesion utilized for occlusal rehabilitation.

Recent advances in adhesive monomers and surface preparation methods allow strong resin adhesion to all intraoral metal surfaces. Resin-metal bond strengths may exceed typical resin-etched enamel bonds. Innovations in prosthetic procedures have resulted. Data for metal adhesion are reviewed and the use of intraoral metal adhesion to finalize an occlusal rehabilitation is illustrated. Included in the metal surface preparations are intraoral sandblasting and intraoral tin plating.