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[Coronary disease: early intervention saves lives. Treatment of acute myocardial infarction in Mantova: results of thirty months of work after the implementation of a province network].

BACKGROUND: Since June 2001, in the province of Mantova, we have undertaken a program for the management of acute myocardial infarction based on the early assessment of patient risk profiles, concerning telematic connections among care centers and on the optimization of in-hospital and out of hospital critical pathways for access to care. MATERIALS AND METHODS: Our network provides connections among the following centers: advanced life support ambulances, seven hospitals, three coronary care units, one cath lab on call 24 h a day for primary angioplasty, and one thoracic surgery division. This program, through its strong telematic platform, allows the early assessment of myocardial infarction and provides primary angioplasty to all high-risk patients, as fibrinolytic treatment is reserved only for low-risk patients admitted in peripheral hospitals. RESULTS: Two hundred and eighty patients with acute myocardial infarction were treated with angioplasty; 224 patients (80%) underwent primary angioplasty, 36 patients (13%) facilitated angioplasty and 20 patients (7%) rescue angioplasty. One hundred and thirty-two patients (47%) were first admitted to Mantova Hospital; 78 patients (28%) were referred to Mantova from peripheral hospitals and 70 patients (25%) were directly transported to the cath lab by advanced life support ambulances. Procedural success was obtained in 98% of patients, with 0.4% intraprocedural mortality. In-hospital mortality was 5.7%, while mortality in cardiogenic shock patients was 36%. The recurrence of acute myocardial infarction occurred in 1% of patients and major bleeding occurred in 2.2% of patients. One patient with cardiogenic shock died during transport. Mean door to balloon time was 67 min with a 42% reduction in the 3rd recruitment period. CONCLUSIONS: This program, developed in the setting of a provincial network for the management of acute myocardial infarction, provided primary angioplasty to all high-risk patients, with a high procedural success rate. Within a few months, time to treatment was minimized by the use of telematic facilities.

Angioplasty, Balloon, Coronary↗

[Telecardiology in the management of acute myocardial infarction: the experience of the provincial network of Mantova].

BACKGROUND: Since June 2001 we activated a program for the treatment of acute myocardial infarction, based on the early assessment of the patient's risk profile, on telematic connection among care centers and optimization of critical pathways for access to care. The aim of this work was to assess the effectiveness of telemedicine in the reduction of time to treatment. METHODS: Mantova, a province of eastern Lombardy (northern Italy) is provided with one single sanitary district with one (tertiary hospital) referring hospital equipped with a cath lab on call 24/24 hours for primary coronary angioplasty (PTCA) and cardiac surgery and 6 community hospitals: 2 with coronary care units, 2 with a cardiology section, and 2 rehabilitation hospitals. The emergency medical system transport, activated 24/24 hours, consists of 6 advanced life support (ALS) ambulances and 11 basic life support (BLS) ambulances (2 with trained nurse staff). Each ALS ambulance is equipped with a semiautomatic defibrillator LIFEPACK 12 coupled with cellular telephone GSM transmission of the 12-lead ECG. RESULTS: In the first 3-year activity of the project 340 patients with acute myocardial infarction underwent primary PTCA: 248 (73%) referred to first aid of the nearest hospital reached either by BLS ambulance or by their own means of transport and were hence transferred to the referring hospital for primary PTCA (group A), while 92 patients (27%) were aided at their own house by ALS ambulances and, after transmission of the 12-lead ECG to the referring coronary care unit, were directly transferred to the cath lab (group B). Decisional delay was 144 +/- 65 min in group A while 74 +/- 37 min in group B. Mean door-to-balloon time was 76 +/- 26 min in group A and 47 +/- 21 min in group B. High incidence of post-procedural TIMI 3 flow was achieved in both groups. In-hospital mortality was 6.8% in group A e 5.4% in group B. CONCLUSIONS: Our data show that patients referring directly to ALS ambulances had a lower decisional delay. Transmission of the patient's ECG and clinical parameters allows an early and accurate diagnosis and assessment of the individual risk profile with a consistent reduction in time to treatment and positive effects on the mortality rate.

Aged↗

[Coronary revascularization in acute coronary syndrome: which technique? which patients? how and when?].

During the last decades, the prognosis of non-ST-elevation acute coronary syndromes has greatly improved. This improvement mainly depends on a better understanding of their pathophysiological background that allowed a remarkable evolution of their diagnostic and therapeutic management. Likewise, invasive strategies have evolved accordingly. Initially, patients with non-ST-elevation acute coronary syndromes had a very conservative approach and coronary revascularization was strongly discouraged during the acute phase. Afterward, as pharmacological therapies and revascularization techniques improved, interventional strategies gradually switched to a careful "delayed invasive approach". Recently, several studies, taking full advantage from the most effective treatments, have demonstrated that an early aggressive strategy (coronary revascularization within 48 hours of symptom onset) could reduce the incidence of cardiac events in patients with non-ST-elevation acute coronary syndromes at medium-to-high risk. These findings made this "early aggressive" strategy very attractive. However, in the real world such a strategy is rarely an option due to several logistical constraints and very often the selection of the therapeutic strategy depends more on resource availability than on patients' risk profile. Therefore, Italian cardiologists should pursue integrated healthcare models in order to overcome such limitations. They should develop critical pathways able to target adequately the patient risk and improve interventional networks where even subjects admitted to peripheral hospitals could benefit from a timely revascularization procedure according to their risk profile. This could reduce treatment disparities and could counteract the vicious circle that tends to privilege interventions in low-risk subjects instead of high-risk patients, like the elderly, women or diabetics.

Acute Disease↗

An amputee critical path.

Approximately 115,000 lower extremity amputations (50 per 100,000 in the general population) were performed in 1985. Successful rehabilitation of these patients is contingent upon comprehensive coordination of in-patient care and education of patients and families, coupled with effective discharge planning and follow-up. In an environment that places emphasis on shortened length of stay, an efficient method to a unified multi-disciplinary approach is more difficult than ever to accomplish. "Critical Pathways" are an effective tool to expedite the communication and planning required to achieve a timely discharge as well as successful rehabilitation.

Amputation, Surgical↗

A role for PI3K-Akt signaling in pulmonary metastatic nodule formation of the osteosarcoma cell line, LM8.

To search for the intracellular signaling pathway critical for the pulmonary metastasis of osteosarcoma, we examined two osteosarcoma cell lines with different metastatic capability, Dunn and LM8. While parental Dunn is poorly metastatic to lung, LM8, derived from Dunn by in vivo selection through pulmonary metastasis, displays clear capability of pulmonary metastasis. We found that LM8 had higher levels of Akt phosphorylation and Ezrin expression than Dunn. In contrast, no clear difference was observed between Dunn and LM8 in other signaling mediators, including MAPK, SAPK and Stat3. In contrast to Dunn, LM8 secreted higher levels of matrix metalloproteinase-2 and -9, showed higher levels of invasiveness and cell motility, and displayed strong pulmonary metastasis. Inhibition of PI3K-Akt signaling in LM8 by a PI3K inhibitor, LY294002, or by a dominant negative form of Akt, resulted in suppression of MMP secretion, in vitro invasiveness, cell locomotion and in vivo pulmonary metastasis. In contrast, expression of an active form of Akt in Dunn substantially activated its MMP secretion, in vitro invasiveness, cell locomotion and in vivo pulmonary metastasis. Taken together, our results demonstrate, for the first time, an important role of Akt signaling in pulmonary metastasis of osteosarcoma.

Cell Line, Tumor↗

Systems analysis of urban wastewater systems--two systematic approaches to analyse a complex system.

This work was aimed at performing an analysis of the integrated urban wastewater system (catchment area, sewer, WWTP, receiving water). It focused on analysing the substance fluxes going through the system to identify critical pathways of pollution, as well as assessing the effectiveness of energy consumption and operational/capital costs. Two different approaches were adopted in the study to analyse urban wastewater systems of diverse characteristics. In the first approach a wide ranged analysis of a system at river basin scale is applied. The Nete river basin in Belgium, a tributary of the Schelde, was analysed through the 29 sewer catchments constituting the basin. In the second approach a more detailed methodology was developed to separately analyse two urban wastewater systems situated within the Ruhr basin (Germany) on a river stretch scale. The paper mainly focuses on the description of the method applied. Only the most important results are presented. The main outcomes of these studies are: the identification of stressors on the receiving water bodies, an extensive benchmarking of wastewater systems, and the evidence of the scale dependency of results in such studies.

Belgium↗

Venous thromboembolism prophylaxis in colorectal surgery.

Patients who undergo colorectal surgery are at a substantially higher risk for deep vein thrombosis (DVT) than their general surgery counterparts. The incidence of DVT in colorectal surgery patients who do not receive prophylaxis is approximately 30%; a four-fold increase exists in the incidence of pulmonary embolism. The precise reasons for the increased risk are uncertain; likely, contributing factors are the need for pelvic dissection, patient positioning (eg, use of stirrups), and indications for surgery (eg, inflammatory bowel disease, cancer). Despite the clear evidence that supports the safety and efficacy of DVT prophylaxis, appropriate preventive measures are frequently not used. Heparin preparations and mechanical compression in combination likely represents the most appropriate prophylactic regimen in these high-risk patients. Standard heparin appears to be as effective as low-molecular-weight heparin and considerably less costly. In the presence of relatively poor adherence to consensus guidelines for prophylaxis, critical pathways or electronic alerts may be useful to facilitate compliance with appropriate preventive measures.

Anticoagulants↗

[Management of acute chest pain in the emergency department].

Acute chest pain is one of the most common symptoms in emergency departments. Immediate assessment is mandatory on arrival in order to ensure the appropriate care. Diagnostic work-up should be based on conventional tools, i.e. clinical presentation, physical examination, electrocardiogram, as well as on modern information, i.e. biochemical markers of myocardial damage or provocative tests. Firstly, physicians should assess the likelihood that signs and symptoms have a cardiac origin secondary to coronary artery disease. Afterwards, the risk for ischemic complications should be stratified. To this end, several scores have been derived from clinical trials in order to improve prediction of outcome. Also, use of critical pathways can improve guideline adherence. In the "real world", a variety of barriers to optimal management of acute chest pain still exists. An agreement on specific protocols is often difficult to achieve between different specialties. Also, no official guidelines on low-risk chest pain patients or patients with non-cardiac chest pain are available. Finally, the minimal data set of diagnostic tools that should be applied in case of acute chest pain in any emergency setting is still lacking.

Acute Disease↗

Two-incision minimally invasive total hip arthroplasty: techniques and results to date.

The two-incision minimally invasive technique for total hip arthroplasty is described in detail, with attention to pearls of technique, for a prospective group of 200 patients, as well as a matched-pair group of 43 patients who underwent either the two-incision procedure or the mini-incision (single-incision posterior) procedure. The importance of a total hip critical pathway is emphasized, and the economic benefits are presented. Results reveal that the two-incision and mini-incision techniques have acceptable complication rates, are cost effective, and are beneficial to the patient, with reduced hospital stays, high patient satisfaction, and earlier return to function.

Arthroplasty, Replacement, Hip↗

Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer.

Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using micro-array. Further studies are needed to collect the data of the mRNA markers used in clinical practice.

Adult↗

[Endocannabinoids as molecular instruments of health promotion].

UNLABELLED: Endocannabinoids may be a physiological model for our self-healin capacities, since they are part of a complex system of natural auto-regulatory processes. This system has been examined via neurobiology, where the experimental invertebrate model is useful. Endocannabinoids, as well as endogenous morphine, activate constitutive nitric oxide (NO) release, which exerts a variety of positive physiological effects. By doing so, we surmise endogenous stress reduction emerges. Therefore, in the context of endocannabinoid auto-regulation, it seems adequate to speak of "health promotion on a molecular level". The convergence of endogenous auto-regulation on NO pathways critically relies upon common or overlapping neurobiological molecular components, as they are represented by limbic reward and motivation mechanisms. To our knowledge, endogenous auto-regulation--involving deep limbic brain activities--plays a crucial role in successful modern strategies of applied and integrative health promotion. More research, however, is necessary before the different aspects of neurobiological science and clinical medicine in the field of prevention may be integrated extensively and with profound reason. CONCLUSIONS: Successful preventive programs, such as integrative medical stress management, include auto-regulative mechanisms on the physiological level. This leads to an interesting research potential, particularly when one considers the long-term effects of applied health promotion and its coupling to motivational neurobiological phenomena.

Amino Acid Sequence↗

Analyses of promoter hypermethylation for RUNX3 and other tumor suppressor genes in nasopharyngeal carcinoma.

BACKGROUND: Aberrant methylation of cytosine in promoter CpG islands is a recognized contributory process to carcinogenesis. This study explores the methylation profile of RUNX3 in combination with p16, RASSF1A, CDH1 and hMLH1 in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Genomic DNA was extracted from 19 fresh frozen NPC biopsies, which were then subjected to bisulfite conversion and methylation-specific PCR for analysis of promoter hypermethylation for the five respective genes. Three cell lines, SNU1, RKO and LS174T, were used as controls. RESULTS: The incidences of promoter methylation were as follows: RUNX3 0/19 (0%), p16 6/19 (32%), RASSF1A 13/19 (68%), CDH1 9/19 (47%) and hMLH1 4/19 (21%). Ninety-five percent of the tumor specimens displayed aberrant methylation in at least one of these genes. No significant correlation between methylation status of these genes and clinical parameters was found. CONCLUSION: Methylation of multiple genes is involved in critical pathways for cancer development in NPC. Promoter hypermethylation for RUNX3 was, however, not present.

Base Sequence↗

Regulated expression of a cell division control-related protein kinase during development.

Protein kinases are important signaling molecules that are known constituents of cellular pathways critical for normal cellular growth and development. We have recently identified a new protein kinase, p58, which contains a large domain that is highly homologous to the cell division control p34cdc2 protein kinase. This new cell division control-related protein kinase was originally identified as a component of semipurified galactosyltransferase; thus, it has been denoted galactosyltransferase-associated protein kinase. In vitro, this protein kinase has been shown to phosphorylate a number of substrates, including histone H1, casein, and galactosyltransferase. In vivo, we have found that this protein kinase affects galactosyltransferase enzyme activity and that it is apparently involved in some aspect of normal cell cycle regulation. In this report, we find that the p58 gene is evolutionarily well conserved and expressed ubiquitously, but to varying extents, in adult tissues. In developmentally staged embryos, p58 expression was elevated early in embryogenesis and then decreased dramatically. In the murine submandibular gland, p58 expression was elevated between day 14 and day 16 post coitus. Expression in the submandibular gland appeared to parallel the proliferation and differentiation of specific cell types as judged by in situ hybridization. These studies indicate that the p58 protein kinase may have a critical function during normal embryonic development and that this protein kinase continues to be expressed in differentiated adult tissues.

Amino Acid Sequence↗

Amnestic disorders. Pathophysiology and patterns of memory dysfunction.

A wide variety of conditions seen in medical practice can produce memory impairment (amnesia). Normal aging, depression, and anxiety are commonly associated with memory difficulties, as are many neurologic conditions. Systemic illnesses can impair memory by injuring vulnerable limbic regions sensitive to hypoxia or hypoglycemia. Commonly used over-the-counter and prescription medications can likewise cause amnesia. These conditions disrupt memory in characteristic ways. Recent studies suggest that immediate, recent, and remote memory functions have different neuroanatomic substrates, as do the processes of registration, retention, and retrieval. New classifications have emerged to explain the evidence for multiple memory subsystems. The neuropharmacology of memory now includes several peptides in addition to cholinergic and noradrenergic pathways. Critical limbic regions have been discovered that mediate memory consolidation, and neuronal mechanisms such as long-term potentiation are being implicated in the unique capacity of these areas to permit new learning to take place.

Adrenocorticotropic Hormone↗

Psoriasis. Leukocytes and cytokines.

Elements of the immune system must take their place alongside other potential mechanisms of psoriasis, such as psoriatic epidermal keratinocytic hyperproliferation, endothelial cell and fibroblast activation and proliferation, abnormal lipid regulation, and transmembrane signalling abnormalities. These data provide support for the concept that cellular immunologic processes are active in a manner that further promotes the patho-physiologic events observed in psoriasis. Thus, therapies useful for psoriasis may have activity on immunologic processes in addition to more traditional mechanistic conceptions of effects on keratinocyte proliferation or other constitutive cell activity. As depicted in Figure 1, UV light, steroids, cyclosporine, and tars have potent inhibitory effects on antigen-presenting cells as well as on T cells. Methotrexate and azathioprine both have immunosuppressive activities, and even retinoids have complex immunomodulatory activity in addition to their ability to alter keratinocyte differentiation (or responsiveness to lymphokines). Cyclosporine has potent effects on T cells after they encounter activating signals such as foreign antigens or autoantigens. Although the T cell actually can become partially activated in the presence of cyclosporine, the drug interferes with the ability of the activated T cell to synthesize and secrete lymphokines (such as IL-2 or gamma-interferon) critical for the initiation and amplification of immune responses to a particular antigen. Although interruption of a single critical pathway improves psoriasis, it is likely that the most effective medications for psoriasis have actions on more than one cell type important in the pathogenesis of the lesion.

Cell Division↗

NADH regulates the gating of VDAC, the mitochondrial outer membrane channel.

Aerobic energy metabolism in cells involves the transfer of reducing equivalents from organic molecules to oxygen. NADH is important as a carrier of these reducing equivalents and as a feedback regulator of glycolysis. We report that micromolar quantities of NADH double the voltage dependence of the mitochondrial channel, VDAC, a critical pathway for the flux of metabolites between the cytoplasm and the mitochondrial spaces. In the presence of NADH, the opening and closing of this channel is more sensitive to changes in membrane potential and thus presumably better able to respond to changes in metabolic conditions. This effect was observed both on a human and two fungal forms of VDAC, indicating a highly conserved regulatory mechanism. NAD+ and other nucleotides tested failed to mimic the action of NADH. This ability of NADH to facilitate VDAC closure could be one mechanism by which glycolysis can suppress oxidative phosphorylation (Crabtree effect).

Amino Acid Sequence↗

Soluble CTLA4Ig modifies parameters of acute inflammation in rat lung allograft rejection without altering lymphocytic infiltration or transcription of key cytokines.

The efficacy of CTLA4Ig in blocking immune activation and allograft rejection (AR) was tested in an aggressive and rapid model of rat lung AR (Brown Norway [BN]-->Lewis [LEW]). CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells. This interrupts the costimulatory pathway critical for complete T cell activation and completion of the AR process. Left single-lung transplants were performed between BN-->Lew. Five allograft recipients were examined in each group. At transplantation, animals received 250 micrograms of CTLA4Ig or 250 micrograms of control Ig intraperitoneally daily until sacrifice. Animals were sacrificed on days 2, 4, and 7 after transplant. Control (BN-->Lew) grafts show irreversible rejection by day 7. Syngeneic (Lew-->Lew) grafts show no AR on day 7. AR episodes were graded histologically (stages 0-IV) and pathologic intensity of inflammation was graded on percentage of involvement. Cytokine transcript levels were measured in control and CTLA4Ig-treated animals (n = 5 in each group) on day 7 using reverse transcriptase polymerase chain reaction techniques. The most profound differences were found on day 7 after transplant. The degree of lymphocytic infiltration was greater in the CTLA4Ig group (perivascular: 4 +/- 0 vs. 2.6 +/- 0.6, peribronchial: 4 +/- 0 vs. 2.2 +/- 0.4, and peribronchiolar: 3.6 +/- 0.5 vs. 2 +/- 0.3, P < 0.01). However, in striking contrast, the stage of AR (3 +/- 0 vs. 4 +/- 0, P < 0.01), vasculitis (1 +/- 0.7 vs. 2.6 +/- 0.6, P < 0.05), hemorrhage (0.4 +/- 0.6 vs. 3.2 +/- 0.4, P < 0.01), and necrosis (0 +/- 0 vs. 2.4 +/- 0.5, P < 0.005) were significantly reduced in animals treated with CTLA4Ig. Since CTLA4Ig blocks Th1 cell activation in vitro, we compared the levels of Th1 inflammatory cytokines IL-2, gamma-IFN, and TNF-alpha in the two models. The intragraft ratios (CTLA4Ig/control) were IL-2:0.77, gamma-IFN: 1.29, and TNF-alpha:1.33. Thus, CTLA4Ig did not significantly block intragraft production of Th1 cytokines on day 7.(ABSTRACT TRUNCATED AT 400 WORDS)

Abatacept↗

A joint hospital/vendor project brings CQI and point-of-care technology to home care.

A joint project team consisting of personnel from Parkview Episcopal Medical Center, Pueblo, Colorado, and Patient Care Technologies, Atlanta, Georgia, a software vendor, codeveloped a point-of-care based system of electronic patient records and administrative data capture for home health care. Well established continuous quality improvement techniques, in use at Parkview for approximately 6 years, guided the development project and the subsequent alpha and beta testing of the system. Significant results to date include an overall productivity gain approaching 20%, the potential to increase annual home care revenue $876,000 with the same staffing level, and an 83% reduction in billing errors. Although not directly measured as a part of the study, the project team believes the quality of charting has improved because it is now done at the point-of-care in the home rather than in the office--some period of time after care is delivered. Anticipated future development includes integration of the home care clinical record with the hospital's clinical data repository and explicit support of critical pathways.

Accounting↗