[Pharmacological Thromboprophylaxis in Acutely Ill Hospitalized Medical Patients]. / Thromboprophylaxie pharmacologique chez les patients hospitalisés pour une affection médicale aiguë.

Venous thromboembolic events (VTE) occur in approximately 50% of cases during or following hospitalization; VTE are a major cause of morbidity and mortality. Thromboprophylaxis for 6 to 14 days with heparins or fondaparinux has been demonstrated to be effective in VTE prevention in patients hospitalized for acute medical illnesses and reduced mobility. Nevertheless, the level of recommendation has been gradually downgraded as the benefit has been mainly demonstrated on the basis of systematic imaging diagnosed events. Direct oral anticoagulants have been assessed only as an extended prophylaxis, and are currently not recommended in medical thromboprophylaxis. Assessing the risk of VTE and bleeding in medical patients is complex. VTE and bleeding risk assessment scores were constructed but have not been validated. In order to improve the adequacy of prescriptions for thromboprophylaxis, the impact of different interventions has been the subject of several studies but these yielded varying results. The aim of this review is to analyze the indications for thromboprophylaxis in a medical setting with the latest available data.

Morfea queloide: respuesta al tratamiento con calcipotriol tópico / Keloidal morphea: good response to topical calcipotriol

La morfea queloide es una rara variante de la esclerodermia localizada. Se sugirió que la misma representa una respuesta queloide a los componentes inflamatorios de la esclerodermia en pacientes genéticamente predispuestos a desarrollar queloides, en áreas del cuerpo con predilección por éstos, aunque sus mecanismos etiopatogénicos continúan siendo desconocidos. Los diagnósticos diferenciales incluyen los queloides espontáneos, el dermatofibroma, las cicatrices hipertróficas y la fibromatosis. Se trata de una entidad refractaria a los tratamientos habituales, por lo que nuestro caso adquiere importancia ante la buena respuesta al calcipotriollocal (AU)

Keloidal Morphea is a rare variant of Scleroderma. It has been suggested that it represents a keloidal reponse to inflammatory components of scleroderma, in genetically predisposed patients to develop keloids, in areas ok the skin that have a high predilection for keloid formation, such as the chest. The differential diagnosis includes spontaneous keloids, dermatomyofibroma, and fibromatosis. There is no known effective treatment for keloidal scleroderma (AU)

The Prader-Willi/Angelman imprinted domain and its control center.

The present review focuses on the recent advances towards understanding the mode of operation of the imprinting center (IC) within the Prader-Willi/Angelman syndromes (PWS/AS) domain. Special emphasis is put on the elucidation of the functional interaction between the two parts of the center, AS-IC and PWS-IC. The recent studies, on which the review is based, reveal cis-acting elements and trans-acting proteins that constitute the two parts of the IC and presumably provide the molecular mechanism for this interaction. AS-IC acquires the primary imprint during gametogenesis by establishing the maternal epigenotype. The unmethylated maternal allele of the AS-IC binds, very likely, a trans-acting factor that confers methylation on the PWS-IC maternal allele after fertilization. It is assumed that the PWS-IC paternal epigenotype, once established, spreads across the entire PWS/AS domain in the soma.

The mouse Snrpn minimal promoter and its human orthologue: activity and imprinting.

BACKGROUND: Microdeletions in chromosome 15q13-15 of Prader-Willi (PWS) and Angelman Syndrome (AS) patients suggested that SNRPN promoter/exon 1, together with a short sequence located approximately 35 kb upstream, constitute an imprinting control centre that regulates the entire 2 Mb PWS/AS imprinted domain. We have recently shown that a minitransgene composed of the human upstream sequence and mouse Snrpn promoter/exon 1 harbours all the elements necessary for establishing and maintaining an imprinted state. RESULTS: Here we describe, using transfection experiments, the Snrpn minimal promoter (SMP), being composed of the entire 76 bp exon 1 and 84 bp of upstream sequence. A 7 bp element (SBE) within SMP that, in its unmethylated state binds a specific protein, is absolutely required for promoter activity. The orthologous human sequence, in spite of the fact that it possesses an identical SBE, failed to display promoter activity in transfection experiments and failed to create a methylated state of the maternal allele. Transgenic experiments reveal that a mutation in SBE of the mouse sequence did not completely abolish methylation of the maternal allele, indicating that sequences outside SBE participate in this process. Replacement of human exon 1 with the mouse orthologue replenished promoter activity, but left the maternal allele in the transgenic experiment unmethylated. The reciprocal chimera, in which mouse exon 1 was replaced by the human orthologue resulted in loss of promoter activity and did not support differential methylation. CONCLUSIONS: The observations made by in vitro and in vivo experiments suggest that several cis elements which are involved in Snrpn promoter activity and the imprinting process are present in the mouse promoter and absent in the human orthologous sequence.

Validation of an instrument designed to assess medical student attitudes toward home care.

OBJECTIVES: To develop and validate an instrument to assess medical students' attitudes toward home care. DESIGN: Survey administration before and following participation in a home care training program. SETTING: Five medical schools in the United States. PARTICIPANTS: 326 third and fourth year medical students. MEASUREMENTS: Factor analysis was performed on all posttests. Domains were tested for internal reliability (Chronbach's alpha). Interdomain correlation was tested. One-way analysis of variance (ANOVA) was used to determine whether the results for each domain differed among the five programs. RESULTS: Using exploratory factor analysis, the original 20-item survey was revised to yield a 14-item survey consisting of four domains (general attitudes, home-based therapies, home care training, and time and reimbursement). Domain intra-item reliability ranged from 0.60 to 0.82. Interdomain correlations were found to be significant with the exception of one comparison (time and reimbursement and home care training). One-way ANOVA showed significant differences between the training programs for two of the four domains (home-based therapies and home care training). For a third domain, time and reimbursement, there was a trend toward differences across the schools (P = 0.06). CONCLUSION: The instrument described in this paper is a reliable and valid instrument for assessing the impact of home care training on medical student attitudes across a series of important domains.

Gene therapy for myocardial angiogenesis: has it come of age?

Vasculogenesis and angiogenesis are the processes responsible for the development of the circulatory system during embryonic and adult life. Vasculogenesis occurs during embryogenesis while angiogenesis refers to blood vessel formation from any preexisting vasculature. Postnatal angiogenesis resumes during reproduction, wound healing, and ischemia. Excess blood vessel formation may contribute to initiating and maintaining many diseases such as chronic inflammatory disorders, tumor growth, restenosis, and atherosclerosis. In contrast. insufficient blood vessel formation is responsible for tissue ischemia, as in coronary artery disease. An increasing number of patients with advanced coronary artery disease remain symptomatic despite maximal interventional, surgical or medical treatment. Ideally, they would benefit most from additional arterial blood supply to ischemic areas of myocardium. Therapeutic angiogenesis, the ability to induce the growth of new blood vessels, is one of the most intriguing new frontiers in interventional cardiology for this growing patient group. Several approaches are currently undergoing intensive experimental investigations or have already entered early clinical trials involving either local angiogenic peptide administration or the transfection of angiogenic genes. Gene therapy for therapeutic myocardial angiogenesis is the most promising synthesis of two emerging technologies. In the following article, we will review the fundamental pathophysiological concepts of gene-based angiogenic therapy, the technical approaches and delivery systems, and the results of the first clinical trials. We will also discuss the controversies and unresolved issues of this new revascularization therapy.

Bypass Without the Surgeon: The Coronary Veins as Arterial Conduits.

More than a century ago, Pratt demonstrated that perfusion of arterial blood through the coronary veins could sustain myocardial viability during acute ischemia. Recognition that atherosclerosis spared the coronary veins and that these vessels frequently followed a parallel course to the corresponding artery provided the necessary stimulus for the development and evaluation of several methods of venous retroperfusion. Although most of these procedures have now been superseded, the coronary veins remain a tempting therapeutic target when direct arterial revascularization is not feasible. Novel percutaneous strategies using these vessels to provide definitive myocardial revascularization have been proposed and extensively tested in animals.

The Coronary Venous System: An Alternate Portal to the Myocardium for Diagnostic and Therapeutic Procedures in Invasive Cardiology.

Retrograde coronary venous perfusion can preserve myocardium during experimental coronary artery occlusion and has been used clinically to deliver oxygenated blood to ischemic myocardium during unstable angina or high-risk percutaneous transluminal coronary angioplasty (PTCA). Retrograde delivery of drugs accelerates coronary thrombolysis, preserves regional myocardial function, and limits infarct size in animal models. Modifications of the coronary venous retroperfusion technique have allowed access to smaller coronary venous branches and minimization of systemic effects of local drug delivery. Retrograde coronary sinus perfusion as an adjunct in high-risk coronary PTCA is limited by its inability to provide systemic hemodynamic support during circulatory collapse. Targeted and specific gene delivery to myocardium with transfection rates superior to intraarterial or systemic injection may be a promising new application for this technique. The coronary venous system can also be used for the noninvasive creation of coronary artery bypasses or the insertion of leads for left ventricular pacing. Contrast-enhanced electron beam computed tomography (EBCT) can noninvasively provide high-resolution imaging of the coronary vessels with qualitative and quantitative information on coronary venous anatomy and coronary arteriovenous relationships and may help in selecting appropriate candidates, anticipating the degree of difficulty of the procedure, and guiding the approach. Therefore, EBCT may become the imaging modality of choice for the assessment of patients considered for such strategies.

Imaging Angiogenesis with Three-Dimensional Microscopic Computed Tomography.

An increasing number of patients with advanced coronary artery disease remain symptomatic, despite maximal interventional or medical treatment. A high demand exists for alternative anti-anginal therapies and ways to improve survival. One of the most intriguing new approaches to increase blood flow to ischemic myocardium is therapeutic angiogenesis, the induction of new vessel growth. Current methods involve local angiogenic growth factor administration, transfection of genes expressing angiogenic proteins, or direct myocardial revascularization. These new therapeutics are undergoing intensive basic and clinical investigation.

Restenosis and Hyperplasia: Animal Models.

Coronary restenosis after percutaneous interventions remains a major clinical problem even in the days of coronary stents. Understanding the pathophysiologic mechanisms and the assessment of therapies for the prevention of restenosis relies on experimental animal models. This article describes the most frequently used animal models of coronary artery restenosis and the differences among them. The variable response to injury in the different models should be considered in the interpretation of the effective therapies before they are transferred into clinical trials. The rat carotid model played an important role as a pioneer in animal models for restenosis but has failed to predict results of clinical restenosis. This lack of predictability highlights a fundamental lack of understanding of the basic molecular mechanisms that control vascular healing after injury.

[Economic aspects of using electron beam computerized tomography]. / Okonomische Aspekte bei der Anwendung der Elektronenstrahlcomputertomographie.

Electron beam computed tomography (EBCT) allows visualization and quantification of calcium in the coronary arteries. This has been demonstrated to correlate well with the overall plaque burden in the coronary arteries. EBCT is, therefore, well suited for the detection of early stages of coronary atherosclerosis. Especially in asymptomatic patients with several risk factors, staging coronary artery disease by coronary calcium, scanning may allow prognostic assessment and guide preventive and therapeutic interventions. To date, only scant data are available regarding the cost effectiveness and the economic impact of this imaging technique. In this manuscript we compare various methods for the diagnosis of coronary artery disease using a theoretical model and review the results of a prospective trial in our emergency room of coronary calcium scanning in patients with acute chest pain. Using Framingham data and prognostic data from long-term follow-up, we discuss the impact of coronary calcification scanning on primary preventive measures and its economical consequences. EBCT is a promising technique which has created a lot of attention due to its ease of application. It is currently undergoing critical appraisal in the medical literature. Further randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA II) to better define its value and limitations in the clinical arena.

Transmyocardial and percutaneous myocardial revascularization: current and future role in the treatment of coronary artery disease.

Transmyocardial revascularization (TMR) is a new treatment modality under evaluation in patients with severely symptomatic, diffuse coronary artery disease, in whom the potential for medical or interventional management has been exhausted. Preliminary clinical trials show improved ischemic symptoms within the first 3 months in about 70% of TMR-treated patients. The original proposed mechanism of surgical or catheter-based TMR (percutaneous myocardial revascularization [PMR]) was that channels mediate direct blood flow between the left ventricular cavity and ischemic myocardium. However, several alternative explanations for the clinical success of TMR have recently been suggested, including improved perfusion by angiogenesis, an anesthetic effect by nerve destruction, and a potential placebo effect. This article reviews the clinical role of TMR/PMR, its possible pathophysiologic mechanisms, and its controversies. It provides an overview of the actual scientific and clinical status of TMR and details future directions.

The experimental animal models for assessing treatment of restenosis.

Coronary restenosis after percutaneous interventions remains a major clinical problem. The assessment of therapies for the prevention of restenosis relies on the use of experimental models. This review describes the most frequently used animal models of coronary artery retenosis and the intraspecies differences among them, particularly in the extent and composition of the neointimal thickening. These differences in neointima formation should be considered in the interpretation of effective antiproliferative therapies before they are transferred into clinical trials.

Administrators' perceptions of nutrition services in home health care agencies.

OBJECTIVE: Ascertain views of home care administrators regarding the need for nutrition services in home care, current status and gaps in dietitian services, and obstacles toward expansion. DESIGN: Mailed survey. SUBJECTS: Members of the National Association for Home Care residing in California, New York, Pennsylvania, Ohio, and Texas. Of the 1,992 questionnaires sent, 402 (20.1%) were completed and used for data analysis. STATISTICAL ANALYSES PERFORMED: Descriptive statistics. RESULTS: Respondents gave high importance to nutrition (6.2 on a 7-point scale), and 39.6% estimated that more than half of their patients were malnourished. Most respondents reported using dietitian services, either as consultants (45.5%) or full-time (5.8%) or part-time (11.9%) employees. Nurses (85.5%) were listed most often as providers of nutrition services; also listed were dietitians (70.6%), pharmacists (17.2%), and physicians (11.2%). More than half of the respondents did not have, but would like to have, a dietitian serve as a nutrition consultant, prepare nutrition care plans, and provide nutrition counseling for patients and caregivers. Primary deterrents noted were lack of reimbursement by third-party payers and lack of physician request. Dietitian services ranked as having the highest value were patient education and counseling, medical nutrition therapy for specific conditions, development of nutrition care plans, staff in-service training, and nutrition assessments. Most home care administrators expected dietitian hours, services, and staff to increase during the next 5 years. APPLICATIONS: The growing home health care market is fertile ground for dietitians. To expand their role in home care, dietitians can position nutrition services as being vital to cost-effective, high-quality care; augment their skills in consultation, training, nutrition support, and outcomes research; strengthen collaborative ties with key home health care professionals; and advocate for Medicare coverage of medical nutrition therapy.

Renal artery pressure gradients in patients with angiographic evidence of atherosclerotic renal artery stenosis.

From October 1979 to August 1991, 231 patients underwent renal artery balloon angioplasty at The Ohio State University Hospitals. Atherosclerotic renal vascular disease was present in 171 of these patients. From this cohort, 138 patients undergoing their first angioplasty had renal artery pressure gradients performed before and after renal artery angioplasty. The demographics of this group included age 66.9 +/- 10 years (+/- SD), male 51%, white 94%, black 6%, diabetes mellitus 28%, systolic blood pressure 157 +/- 26 mm Hg, diastolic blood pressure 86 +/- 13 mm Hg, standard daily doses of antihypertensive medications 4.2 +/- 3, and serum creatinine 2.6 +/- 2.3 mg/dL. Plasma renin activity was measured in 25 patients and was shown to be elevated in 16. The renal artery stenoses were main renal artery 75%, orificial 22%, distal renal artery 1.4%, and combinations of the above 2.2%. Solitary kidneys were present in six patients (4.3%). Bilateral renal artery stenosis was present in 45% of patients and bilateral angioplasties were performed in one third of these patients. The preangioplasty systolic blood pressure gradient was 109 +/- 50 mm Hg (range, 20 to 230 mm Hg) and the postangioplasty renal artery pressure gradient was 12 +/- 16 mm Hg (range, 0 to 78 mm Hg) (P < 0.001). There were no complications related to measurement of the pressure gradients. The magnitude of the renal artery pressure gradients did not correlate with blood pressure level, number of antihypertensive medications, or serum creatinine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase-shifted surface-acoustic-wave resonator.

The spatial distribution of the surface-acoustic-wave (SAW) intensity across a phase-shifted transducer-resonator is studied. A coupled-mode analysis of this structure shows that a highly confined mode can be excited in a pi/2 shifted resonator. Experimental verification of this conclusion was obtained in a LiNbO(3) pi/2 shifted resonator, in which the SAW intensity was measured. The concentration factor (the ratio of the maximum to average SAW intensity) can be ~10 for reasonably long resonators.

Phase I clinical trial of carbetimer.

Carbetimer (carbethimer, N-137, NED-137, carboxyimamidate) is a low molecular weight polyelectrolyte with antitumor activity in a variety of tumor models. This phase I trial evaluated a single dose of carbetimer infused over 1-2 h every 28 days. Forty-three patients received 71 courses of the drug at doses ranging from 180 to 8500 mg/m2. The dose-limiting toxicity was hypercalcemia (serum calcium greater than 12.5 mg/dl) noted in two of three patients at a dose of 8500 mg/m2. Serum calcium levels between 10.5 and 12.5 mg/dl were noted in an additional three patients treated at doses greater than or equal to 1600 mg/m2. Calcium balance studies in three patients treated at 6500 mg/m2 revealed an increase in urinary cyclic AMP and phosphate excretion after treatment accompanied by a mild elevation of serum parathyroid hormone. Immunological studies in these patients revealed a statistically significant increase in the percentage of peripheral T-helper cells. An increase in the T-helper/suppressor cell ratio was observed in two of the three patients studied. Interleukin 2 production by phytohemagglutinin-stimulated peripheral mononuclear cells was increased in two of three patients. One patient with a renal cell carcinoma showed a mixed response. The recommended dose for phase II trials as assessed from this study is 6500 mg/m2 as a single dose every 28 days.