Heart Failure After Myocardial Infarction: Clinical Implications and Treatment

Heart failure is a frequent complication of myocardial infarction. Several factors, such as recurrent myocardial ischemia, infarct size, ventricular remodeling, stunned myocardium, mechanical complications, and hibernating myocardium influence the appearance of left ventricular systolic dysfunction after myocardial infarction. Importantly, its presence increases the risk of death by at least 3- to 4-fold. The knowledge of the mechanisms and clinical features are essential for the diagnosis and treatment of left ventricular dysfunction and heart failure after myocardial infarction. Therefore, this review will focus on the clinical implications and treatment of heart failure after myocardial infarction.

Caroticoclinoid foramen in human skulls: incidence, morphometry and its clinical implications

The caroticoclinoid foramen is an inconstant structure, formed by the union of the anterior and middle clinoid processes. The aim of this study was to perform an incidence and morphometry of the caroticoclinoid foramen in Brazilian human skulls and discuss its clinical implications. Eighty dry human skulls with sex distinction were used, and 3 groups of incidence were determined: General, sex, and sides. The morphometry was performed using a manual caliper and the major diameter of the foramina was measured; the values were also divided in general, according to sex and sides. The incidence of skulls with at least one foramen was 8.5%. According to the sides, 8.5% of the skulls showed foramen on the right side and 2.5% on the left. We found 2.5% of the skulls with bilateral foramen and 6.25% with unilateral foramen. In relation to sex, the foramens were found in 5% of male skulls and 12.5% of female skulls. The major diameter of this structure presented on mean, values of 5.23 mm on general, 5.18 mm on the right side and 5.35 mm on the left, 5.30 mm in male skulls and 5.18 mm in female skulls. The anatomical characteristics of this foramen should be considered in view of its clinical implications associated with neurosurgery as clinoid process removal, and symptoms as headache due to internal carotid artery alterations in this region. In conclusion knowledge of this structure supports the diagnosis and treatment of clinical complications related to this variation.

Morphological characteristics of foramen of Vesalius and its relationship with clinical implications

The aim of this study was to evaluate the incidence as well morphometry of the foramen of Vesalius in human skulls and analyzing their clinical importance. Dry human skulls (n = 80) and with gender distinction were used (40 male and 40 female). The results demonstrates an total incidence of 40%, 13.75% skulls with the bilateral presence of the foramen, 26.25% skulls with the unilateral presence of the foramen, 31.25% skulls with foramen only of the right side, 22.50% skulls with foramen only of the left side, 25% masculine skulls with at least 1 foramen and 52.25% skulls with at least 1 foramen. The morphometry showed an average diameter of 1.457 ± 1.043 mm on the right and 1592 ± 0938 mm to the left. The average distance to the foramen ovale was 1.853 ± 0.303 mm on the right side and 2.464 ± 0.311 mm on the left. It can be concluded that a deepened anatomical study of the foramen of Vesalius collaborates not only for anatomical knowledge of this structure, but also in clinical situations involving this foramen.

Incidence of the ossified pterygoalar ligament in Brazilian human skulls and its clinical implications

The ossified pterygoalar ligament is formed between the lateral lamina of the pterygoid process and the infratemporal surface of the sphenoid bone or its greater wing and was not connected to the sphenoid spine. The aim of this study was to evaluate the incidence of the ossified pterygoalar ligament in Brazilian human skulls and analyzing its clinical importance. 183 Brazilian adult (between 30 to 60 years old) dry human skulls were evaluated. Was evaluated the incidence of skulls with complete or partial ossification of the pterygoalar ligament, bilaterally and unilaterally and in the presence on the right and left sides. Were found 5 skulls had the ossified pterygoalar ligament, resulting in an overall incidence of 2.73%. There was 1 skull in the presence of the incomplete ossification of the pterygoalar ligament, unilaterally and on the left side resulting in incidence of 0.54%. There were 4 skulls in the presence of the complete ossification of the pterygoalar ligament, unilaterally and on the right side resulting in incidence of 2.18%. The ossified pterygoalar ligament is a major cause of the entrapment of the lingual nerve or a branch of the mandibular nerve and may cause mandibular neuralgia. The incidence of the ossified pterygoalar ligament and the pterygoalar foramen is low in the Brazilian population. However, these structures have clinical significance as this ligament establish relationships with the ovale foramen and difficulty in accessing in this foramen in a therapeutic approach.

Paracoccidioides lutzii sp nov.: biological and clinical implications

Paracoccidioides lutzii, formerly known as 'Pb01-like' strains in the P. brasiliensis complex, is proposed as a new species based on phylogenetic and comparative genomics data, recombination analysis, and morphological characteristics. Conidia of P. lutzii are elongated, different from those of P. brasiliensis. P. lutzii occurs in the central and northern regions of Brazil. Studies comparing P. brasiliensis and P. lutzii may have significant clinical consequences for the diagnosis and treatment of paracoccidioidomycosis.

Obstacles to Inter-Racial Understanding: Some Clinical Implications for Mental Health Practitioners in Predominantly White Institutions

in the context of predominantly white institutions. In this paper concepts such as projection, projective identification, splitting, scapegoating, superiority and denial will be employed to illustrate why racial prejudice is a deeply-rooted collective psychological disorder that affects even educated mental health practitioners. Clinicians have an ethical responsibility to demonstrate cultural sensitivity and empathy when working with minority clients, colleagues, staff and students, to examine and root out their own prejudices, and to encourage others to do the same.

Incidence of small lymph node metastases with evidence of extracapsular extension: clinical implications in patients with head and neck squamous cell carcinoma

Small lymph nodes (LN) show evidence of extracapsular extension (ECE) in a significant number of patients. This study was performed to determine the impact of ECE in LN 7 mm as compared with ECE in larger LN.

Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates

The gastrin-releasing peptide receptor (GRPR) has emerged as an attractive target for both therapeutic and diagnostic appliances, but has only insufficiently been characterized in the human prostate so far. The aim of this study is to profile GRPR in a large cohort and correlate it with clinicopathologic and molecular parameters.

Relative bone width of the edentulous maxillary ridge. Clinical implications of digital assessment in presurgical implant planning

Healthy, well-structured mucosa may clinically disguise atrophic jawbone in preimplant diagnosis.

Central hypersensitivity in chronic pain: mechanisms and clinical implications

The available literature consistently shows increased pain sensitivity after sensory stimulation of healthy tissues in patients who have various chronic pain conditions. This indicates a state of hypersensitivity of the CNS that amplifies the nociceptive input arising from damaged tissues. Experimental data indicate that central hypersensitivity is probably induced primarily by nociceptive input arising from a diseased tissue. In patients, imbalance of descending modulatory systems connected with psychologic distress may play a role. There is experimental support in animal studies for the persistence of central hypersensitivity after complete resolution of tissue damage. This is particularly true for neuropathic pain conditions, whereby potentially irreversible plasticity changes of the CNS have been documented in animal studies. Whether such changes are present in musculoskeletal pain states is at present uncertain. Despite the likely importance of central hypersensitivity in the pathophysiology of chronic pain, this mechanism should not be used to justify the lack of understanding on the anatomic origin of the pain complaints in several pain syndromes, which is mostly due to limitations of the available diagnostic tools. Treatment strategies for central hypersensitivity in patients have been investigated mostly in neuropathic pain states. Possible therapy modalities for central hypersensitivity in chronic pain of musculoskeletal origin are largely unexplored. The limited evidence available and everyday practice show, at best, modest efficacy of the available treatment modalities for central hypersensitivity. The gap between basic knowledge and clinical benefits remains large and should stimulate further intensive research.

[Platelet inhibition and activation. Mechanisms and clinical implications.]

The sensitivity to activation of platelets is part of the delicate equilibrium differentiating hemostasis from thrombosis. Under physiological conditions it is maintained by downregulating platelet activity and removing agonists. Under pathologic conditions the clinician tries to restore this equilibrium with pharmaceutical drugs. The results obtained by such treatments are steadily improving but there is still need for better knowledge of the mechanisms involved and for alternative inhibitors.

Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.

Incidence and clinical implications of stent fractures of the Xpert self-expanding nitinol stent in infrainguinal arteries

BACKGROUND: Different stents in infrainguinal arteries have recently been associated with stent fractures and unfavorable clinical outcome, although data is limited regarding fractures of the Xpert selfexpanding nitinol stent. Thus, purpose of the present investigation was to evaluate its incidence and clinical implications in lower limb arteries. PATIENTS AND METHODS: Fifty-three consecutive patients (53 limbs) with peripheral arterial disease underwent secondary Xpert stent implantation due to suboptimal primary balloon angioplasty (PTA). Median age was 76 years. Stent fractures were evaluated by plain X-ray at median follow-up of 16 months. Stent patency was assessed by duplex ultrasound and sustained clinical improvement was defined as improvement of the ABI of > or = 0.10 together with improvement of at least one Rutherford class above the baseline finding throughout follow-up. RESULTS: Median length of femoropopliteal and infrapopliteal lesion was 3.0 and 2.3 cm, respectively. Sixtyfive stents were implanted in 43 limbs with femoropopliteal and 10 stents in 10 limbs with infrapopliteal lesion, respectively. Stent fractures occurred in 3 of 43 limbs (7.0%) of patients with femoropopliteal lesion with stent-based fracture rate of 4.6%. All fractured stents showed multiple struts fractures and occurred in the distal and middle superficial femoral artery. No stent fracture was observed in infrapopliteal lesions. The fractured stents were not associated with any clinical deterioration. Sustained clinical improvement was 71.0% and 54.6% for femoropopliteal and infrapopliteal lesions, respectively. Stent patency assessed by duplex was 65.2 and 63.9% for femoropopliteal and infrapopliteal lesions, respectively. CONCLUSIONS: Fractures of the Xpert stent were seldom and not associated with unfavorable clinical outcome at midterm follow-up.

DEFINING THE ROLE OF EGFR ACETYLATION IN CELLULAR PROCESSES: CLINICAL IMPLICATIONS

Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor and plays a pivotal role in regulating cell growth, differentiation, cell cycle, and tumorigenesis. Deregulation of EGFR causes many diseases including cancers. Intensive investigation of EGFR alteration in human cancers has led to profound progress in developing drugs to target EGFR-mediated cancers. While exploring possible synergistic enhancement of therapeutic efficacy by combining EGFR tyrosine kinase inhibitors (TKI) with other anti-cancer agents, we observed that suberoylanilide hydroxamic acid (SAHA, a deacetylase inhibitor) enhanced TKI-induced cancer cell death, which further led us to question whether SAHA-mediated sensitization to TKI was associated with EGFR acetylation. What we know so far is that SAHA can inhibit class I and II histone deacetylases (HDACs), which could possibly preserve acetylation of underlying HDAC-targeted proteins including both histone and non-histone proteins. In addition, it has been reported that an HDAC inhibitor, TSA, enhanced EGFR phosphorylation in ovarian cancer cells. EGFR acetylation has also been reported to play a role in the regulation of EGFR endocytosis recently. These observations indicate that there might be an intrinsic correlation between acetylation and phosphorylation of EGFR. In other words, the interplay between EGFR acetylation and phosphorylation may contribute to HDAC inhibitors (HDACi)-augmented EGFR phosphorylation. In this investigation, we showed that CBP acetyltransferase acetylated EGFR in vivo. In response to EGF stimulation, CBP rapidly translocated from the nucleus to the cytoplasm. We also demonstrated protein-protein interaction between CBP and EGFR as well as the enhancement of EGFR acetylation by CBP. Moreover, EGFR acetylation enhanced EGFR tyrosine phosphorylation and augmented its association with Src kinase. Acetylation-deficient EGFR mutant (EGFR-K3R) significantly reduced the function and activity of EGFR. Furthermore, ectopic expression of EGFR-K3R mutant abrogated its ability to respond to EGF-induced cell proliferation, DNA synthesis, and anchorage-independent growth using cell-based assays and tumor growth in nude mice. In addition, we demonstrated that EGFR expression was associated with SAHA resistance in the treatment of cancer cells that overexpress EGFR. The knockdown of EGFR in MDA-MB-468 breast cancer cells could sensitize the cells to respond to SAHA. The overexpression of EGFR in SAHA-sensitive MDA-MB-453 breast cancer cells rendered the cells resistant to SAHA. Together, these findings suggest that EGFR plays an important role in SAHA resistance in breast carcinoma cells that we tested. The combination therapy of HDACi with TKI has been proposed for treating cancers with aberrant expression of EGFR. The evidence from pre-clinical or clinical trials demonstrated significant enhancement of therapeutic efficacy by using such a combination therapy. Our in vivo study also demonstrated that the combination of SAHA and TKI for the treatment of breast cancer significantly reduced tumor burden compared with either SAHA or TKI alone. The significance of our study elucidated another possible underlying molecular mechanism by which HDACi mediated sensitization to TKI. Our results unveiled a critical role of EGFR acetylation that regulates EGFR tyrosine phosphorylation and may further provide an experiment-based rationale for combinatorial targeted therapy.