Troponin I elevation after pericardiocentesis for cardiac tamponade: a role for myocardial strain?
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Aged↗
Biomedical subjects
P Dias
Publications and source records attributed to P Dias.
Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy.
The benefits of tailoring therapy with vasodilators in patients with severe heart failure are well documented, but this may lead to neurohormonal activation and sodium retention. Renal dopamine has local natriuretic actions and interacts with other hormones involved in renal sodium handling. The aim of the present work was to determine the effects of arterial underfilling induced by vasodilator therapy on renal sodium handling, neurohormonal activation and the activity of the renal dopaminergic system in patients with severe heart failure. For this purpose we monitored haemodynamic parameters, plasma levels of type B natriuretic peptide (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine, and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its metabolites, before initiation of sodium nitroprusside therapy and every 6 h thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme (ACE) inhibition, in 10 male patients with severe heart failure. The results of nitroprusside therapy were a marked increase in cardiac index and a substantial decrease in systemic vascular resistance index. Plasma levels of BNP decreased significantly, while PRA, noradrenaline and aldosterone showed marked increases, resulting in a substantial reduction in urinary sodium excretion. Creatinine clearance was not affected. Urinary dopamine and dopamine metabolites increased in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary sodium returned to baseline values, while urinary dopamine was markedly reduced. These results suggest that the renal dopaminergic system is activated in patients with severe heart failure by stimuli leading to sodium renal reabsorption.
Aged↗
Acute pulmonary embolism.
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Acute Disease↗
[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].
BACKGROUND: Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. OBJECTIVE: Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. DESIGN: Prospective study. PATIENTS: One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. RESULTS: Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. CONCLUSION: These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.
Aged↗
Prognosis in patients with heart failure and preserved left ventricular systolic function.
BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.
Aged↗
Echocardiographic patterns and prognosis in heart failure.
BACKGROUND: There are many variables with prognostic value in patients with heart failure (HF). Those related to left ventricular function are among the most important. Recently, the evaluation of the patterns of ventricular filling by pulsed Doppler echocardiography has been studied as a variable with prognostic value. OBJECTIVES: To evaluate the prognostic value of echocardiography variables (diastolic and systolic) in patients with HF. These variables were analysed in respect to hospital admission for cardiovascular reasons or death. MATERIAL AND METHODS: We evaluated 157 consecutive patients with HF and included 110 patients who were in sinus rhythm. The mean age was 68.2 +/- 0.9 years. HF was ischemic in 52.7%. Patients underwent echocardiography examination within the week of reference. The patients were grouped according to left ventricular (LV) systolic dysfunction (LV ejection fraction < 40%). We also classified patients in two groups according to the presence of a restrictive pattern in diastolic transmitral flow profile. Finally, we classified all patients in four groups according to their systolic function and diastolic pattern: Group I--systolic dysfunction and restrictive ventricular filling pattern. Group II--systolic dysfunction without restrictive ventricular filling pattern. Group III--without systolic dysfunction with restrictive ventricular filling pattern. Group IV--without systolic dysfunction without restrictive ventricular filling pattern. The events were death or hospital admission. The mean follow up time was 625 +/- 55 days. We did a statistical analysis and for all tests a p value < 0.05 was considered statistically significant. RESULTS: We found impaired LV systolic function (systolic HF) in 73.6% and restrictive ventricular filling pattern in 45.5%. During the follow-up 41.8% died or were admitted to hospital. Patients with systolic HF had lower admission free survival rate. Patients with restrictive ventricular filling pattern had lower admission free survival rate than those without. Group I had lower admission free survival rate than Group II and Group IV. Group IV had a higher admission free survival than all other Groups. CONCLUSIONS: These results support and expand previous observations that diastolic function variables, such as the pattern of ventricular filling (namely the restrictive) have independent prognostic value in patients with HF.
Aged↗
Poisoning with calcium channel blockers--a case report and review of the literature.
The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. We present a clinical case of bradycardia and shock of unknown cause, which came to be revealed a poisoning by 3240 mg of slow-release diltiazem, managed with temporary transvenous pacing and dopamine in high concentration. We make a review of the cardiovascular manifestations of the three classic calcium channel blockers: verapamil, diltiazem and nifedipine; namely, hypotension, rhythm and conduction disturbances. We point out the late appearance of the beginning of manifestations with the use of slow releasing formulations. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. The bradyarrhythmias are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. If the intoxication causes depression of cardiac contractility, the use of calcium or/and glucagon is indicated. If there is refractoriness with these measures, catecholamines should be employed. There are alternative and adjuvant drugs such as amrinone, insulin-glucose, 4-aminopyridine and calcium entry promoters. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest.
Aged↗
Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass.
Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein.
Antibodies, Monoclonal↗
Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine.
1. This case report of a Chinese male schizophrenic patient describes new side effects that have not been documented previously for patients treated with clozapine. At certain doses of clozapine, the patient showed direct adverse reactions, which include a combination of hyperglycemia, hyperlipemia, and periodic paralysis. 2. In a four-year study of this patient who had no previous episodes of diabetes in his or his family history, the authors found that these symptoms disappeared upon withdrawal of clozapine and relapsed with re-treatment of the drug. This study indicates that hyperglycemia, hyperlipemia, and periodic paralysis may need to be monitored on patients treated with clozapine.
Adult↗
Predictors of prognosis in patients with stable mild to moderate heart failure.
BACKGROUND: A number of prognostic indexes have been developed to predict the outcome of patients with severe heart failure (HF). In patients with mild to moderate HF, however, there is no consensus regarding the usefulness of such indexes. The goal of this study is to determine the prognostic value of selected clinical variables in the latter group of patients. METHODS AND RESULTS: We prospectively evaluated the prognostic value of the functional capacity evaluation, the ventricular function, biochemical metabolic indicators, and brain natriuretic peptide (BNP) levels in 139 consecutive patients with mild to moderate HF. A clinical and echocardiographic examination (M-mode, 2D and pulsed Doppler of the mitral inflow); a 6-minute walk test; and a determination of serum sodium, uric acid, and BNP levels were performed. Death by any cause was predefined as the study end-point. Variables found to be related with survival in a univariate Cox regression analysis were NYHA class; ischemic origin for HF; left ventricular ejection fraction; deceleration time of the E wave; and 6-minute walk distance, serum sodium, uric acid, and BNP levels. In a multivariate analysis, ischemic origin of HF, 6-minute walk distance, deceleration time of the E wave, and BNP levels were found to be independent prognostic factors. The clustering of the independent prognostic factors was associated with the worse prognosis. CONCLUSIONS: These results suggest that the noninvasive evaluation used in this study and in our population of patients with mild to moderate HF allows the identification of individuals with the worst prognosis. The selected variables might prove to be very helpful in stratifying HF patients and identifying those that might benefit the most from a HF management program.
Activities of Daily Living↗
Evaluation of brain natriuretic peptide in the diagnosis of heart failure.
A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.
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alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings.
The proteasomes have a central role in catalysing protein degradation among both prokaryotes and eukaryotes. The 20 S proteasome constitutes their catalytic core. In studying the structure of Trypanosoma brucei 20 S proteasomes, we isolated by two-dimensional (2D) gel electrophoresis a 27 kDa subunit protein with an estimated pI of 4.7 and subjected it to mass spectrometric analysis. A tryptic peptide sequence from the protein was found identical with that of the rat alpha5 subunit. With the use of antiserum against T. brucei 20 S proteasomes to screen a T. b. rhodesiense lambda expression cDNA library, we obtained a cDNA clone encoding a full-length protein of 246 amino acid residues with a calculated molecular mass of 27174 Da and a pI of 4.71. It bears 50. 0% and 46.3% sequence identity with rat and yeast proteasome subunit alpha5 respectively, and matches all the peptide sequences derived from MS of the 2D gel-purified protein. The protein is thus designated the alpha5 subunit of T. brucei 20 S proteasome (TbPSA5). The recombinant protein, expressed in plasmid-transformed Escherichia coli, was found in a 27 kDa monomer form as well as polymerized forms with estimated molecular masses ranging from 190 to 800 kDa. Under the electron microscope, the most highly polymerized forms bear the appearance of cylinders of four-stacked heptamer rings with an estimated outer diameter of 14.5 nm and a length of 18 nm, which were immunoprecipitable by anti-(T. brucei 20 S proteasome) antiserum. In view of the documented self-assembly of the archaeon proteasome alpha subunit into double heptamer rings and the spontaneous assembly of the two alpha subunits from the 20 S proteasome of Rhodococcus erythropolis, the self-assembly of the T. brucei alpha subunit might reflect a common feature of proteasome biogenesis shared by prokaryotes and primitive eukaryotes such as the trypanosomes but apparently lost among the higher forms of eukaryote such as the yeast and the mammals.
Amino Acid Sequence↗
Activated astrocytes display increased 5-HT2a receptor expression in pathological states.
In human brain tissues from patients dying with cerebral infarction, hypertensive encephalopathy, Alzheimer's disease, Huntington's disease, frontotemporal dementia, and Creutzfeldt-Jakob disease there is an activation of astrocytes. Such activated astrocytes display GFAP and strong 5-HT(2A), but not 5-HT(2B) or 5-HT(2C), receptor immunoreactivity; this 5-HT(2A) reaction has not been observed in normal, nonactivated astrocytes. It is suggested that an up-regulation of 5-HT(2A) receptors may be part of an early response reaction in astrocytes, possibly designed to maintain homeostasis or to induce secondary message pathways involving trophic factors or glycogenolysis.
Aged↗
Differential expression of serotonin 5-HT2 receptors during rat embryogenesis.
Serotonin (5-HT) is a neurotransmitter that also functions as a hormone and a growth factor. 5-HT is involved in numerous physiological actions and displays complex pharmacological properties. As a growth factor, 5-HT plays a role in cell proliferation and differentiation of neuronal and nonneuronal tissue and it transduces its signals through more than fourteen subtypes of 5-HT receptors. Since determination of the expression and distribution is important for understanding the role of the 5-HT receptors, we have developed an RNase protection assay (RPA) that allows the simultaneous analysis of 5-HT2AR, 5-HT2BR, and 5-HT2CR per sample of RNA. This multiprobe set also comprises probes for two house-keeping genes, L32 and GAPDH, which control for sample-loading errors. Using this RPA probe set, we have examined the relative expression of 5-HT2AR, 5-HT2BR, and 5-HT2CR in rat embryos inclusively from embryonic day (ED) 9 to 21 of development. Our data indicate that 5-HT2AR levels gradually increased from ED11 to ED21. The expression of 5-HT2BR was decreased between ED9 to ED11 then remained relatively constant through ED21. 5-HT2CR was initially expressed at residual levels between ED9 and ED12 but dramatically increased to a peak level at ED13, then decreased by ED17. Expression of the 5-HT2 receptors in these tissues was confirmed independently by RT-PCR indicating that there is developmental regulation in the expression of these receptors. The 5-HT2R multiprobe assay will be useful for detecting relative changes in the expression of these receptors in developmental, normal and pathological tissues as well as for monitoring relative changes in expression resulting from the use of pharmaceutical agents.
Animals↗
Development and characterization of monoclonal antibodies specific to the serotonin 5-HT2A receptor.
Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT2A receptor. To generate MAbs against 5-HT2AR, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT2AR recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT2AR, rat and human brain lysate, and lysate from cell lines transfected with 5-HT2AR cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT2AR N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT2AR in lysates from rat brain and a 5-HT2AR-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT2AR but not with recombinant 5-HT2BR and 5-HT2CR. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies.
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Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas.
MyoD1 expression is a distinguishing characteristic of rhabdomyosarcoma. In this study, distinct methylation alterations were identified in the 5' flanking region of the MyoD1 gene from the two major subtypes, ie, alveolar and embryonal rhabdomyosarcoma. The MyoD1 methylation patterns of 26 rhabdomyosarcomas were compared with that of normal skeletal muscle and nonmuscle specimens by Southern blot analysis using methylation-sensitive restriction enzymes HhaI and HpaII. A 5-kb region immediately upstream of the MyoD1 coding sequence was found to be methylated in adult muscle and all nonmuscle tissues tested. The MyoD1 upstream region was unmethylated in the majority of the alveolar rhabdomyosarcomas (13 of 15, 87%) examined in this study. In contrast, 10 of 11 (91%) embryonal rhabdomyosarcomas showed a methylation pattern that was also observed in fetal muscle cells, in which the CpG sites in the MyoD1 upstream region were partially methylated. Our data suggest that the methylation status of the MyoD1 upstream CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable implications for its differential diagnosis.
Adolescent↗
Mutation of Thr115 in MyoD positively regulates function in murine fibroblasts and human rhabdomyosarcoma cells.
Committed skeletal muscle myoblasts undergo terminal differentiation when shifted from a high-mitogen medium to a low-mitogen medium. However, expression of the myogenic regulatory factor MyoD seems to be similar in proliferating and differentiating cells, suggesting that its function is attenuated in proliferating myoblasts. To further understand the potential mechanisms that may attenuate MyoD function, we have examined the effect of posttranslational modification. By analogy with myogenin, we have examined the role of phosphorylation in regulating the function of MyoD. MyoD contains two putative protein kinase C (PKC) phosphorylation sites (Thr115 and Ser200). The former site is analogous to Thr85 within the highly conserved basic domain of myogenin that has been demonstrated to negatively regulate the myogenic differentiation functions of myogenin. To test whether hyperphosphorylation of the same PKC site in MyoD would attenuate its function, we generated a mutant MyoD with a single amino acid substitution (Thr115-Ala) that disrupts the PKC phosphorylation site (Thr115) within the conserved basic domain. Wild-type and mutant MyoD were introduced into cells using an E1, E3-deleted adenoviral vector. In mouse C3H10T1/2 fibroblasts, both wild-type and mutant MyoD induced terminal myogenic differentiation when growth factors were withdrawn from the cell culture. Consistent with these results, nuclear extracts from infected cells, but not those from uninfected cells, demonstrated complex formation with an oligonucleotide containing an E-box consensus sequence. Growth arrest was associated with the up-regulation of p21cip1, cell fusion to multinucleated myotubes, and the expression of a muscle differentiation marker (myosin heavy chain). On the other hand, when infected cells were maintained under high mitogenic conditions (in the presence of 10% fetal bovine serum), the expression of wild-type or mutant MyoD slowed cell growth and induced p21cip1. Only mutant MyoD caused cell fusion, myosin heavy chain expression, and altered mobility of the E-box oligonucleotide in gel shift assays. Furthermore, after infection, MyoD was phosphorylated, and phosphothreonine was detected in wild-type MyoD immunoprecipitated only from C3H10T1/2 cells grown under high mitogenic conditions. These results suggest that Thr115 may play an important role in the regulation of MyoD function under conditions of high mitogenesis. MyoD was also phosphorylated in malignant rhabdomyosarcoma (RMS) cells in which MyoD function was attenuated. Phosphothreonine was also detected in MyoD immunoprecipitates. Rh30 alveolar RMS cells were infected with an adenovirus expressing either wild-type or mutant MyoD. In contrast to the results in fibroblasts, when overexpressed in malignant Rh30 RMS cells, mutant MyoD arrested cell growth without inducing p21cip1 and caused cell fusion. However, no muscle differentiation markers were detected, indicating that an overexpression of mutant MyoD lacking Thr115 caused Rh30 cells to become quiescent and recapitulate at least some aspects of myogenesis (cell fusion).
Adenoviridae↗