Minimally invasive cardiac output monitoring in intensive care unit.
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Biomedical subjects
Publications and source records attributed to A Granata.
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Imaging techniques, especially ultrasonography and Doppler, can give an effective assistance in the differential diagnosis of acute renal failure (ARF). An resistance Index (RI) value >0.75 is reported as optimal in attempting differential diagnosis between acute tubular necrosis (ANT) and prerenal ARF. In hepatorenal syndrome (HRS) RIs is very increased. In some renal vasculitis, as nodose panarteritis (PN), hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), parenchymal perfusion is reduced and RI increased. In lupus nephritis the RI values are correlated with creatinine level and normal RI are considered as a good prognostic tool. In acute primitive or secondary glomerulonephritis (GN), RI value is normal, with diffuse parenchymal hypervascularization. In acute crescentic and proliferative GN and tubulo-interstitial disease, color Doppler (CD) and power Doppler (PD) reveal a decreased renal parenchymal perfusion, which correlates with increased RI values. In acute thrombosis of renal artery, US color Doppler (DUS) reveals either an absence of Doppler signal or a tardus-parvus pulse distal to the vascular obstruction. In this situation it is possible to visualize hyperthropic perforating vessels that redirect their flow from the capsular plexus to the renal parenchyma. In acute thrombosis of the renal vein Doppler analysis of parenchymal vessels reveals remarkable RI values, sometimes with reversed diastolic flow. In postrenal ARF an adjunct to the differentiation between obstruction and non obstructive dilatation can be found through RIs. Diagnostic criteria of obstruction as reported by literature are: RI>0.70 in the obstructed kidney and, mostly, a difference in RI between the 2 kidneys >0.06-0.1.
BACKGROUND: Ultrasonic wave propagation in human tissues is not linear. As a consequence, harmonic waves, whose frequency is a multiple (harmonic) of the emitted frequency, are generated. Tissue Harmonic Imaging (THI) processes only the second harmonic frequency in order to improve the signal-to-noise ratio of the received signal. The study was aimed at investigating the impact of THI on the detection of the Left Ventricular (LV) endocardial border. Attention was paid to determine which LV walls were analysed more clearly with THI rather than with conventional Fundamental Frequency Imaging (FFI). METHODS: We compared the FFI and the THI visualization of the 16 LV segments and of the 6 LV walls in 30 consecutive patients by scoring the images as bad, sufficient or good. The equipment used was a GE Vingmed System Five (Orten, Norway). RESULTS: Images were good in 85% of segments explored with THI, whereas FFI provided good images in 47% of segments (p<0.001). From the apical window, visualization of the apex, lateral wall and anterior wall significantly improved with THI; using the parasternal approach, imaging of posterior wall was definitely better with THI than with FFI. CONCLUSIONS: THI enhances both endocardial visualization and global image quality. Tech-nical development, however, increases the diagnostic possibilities of echocardiography but does not substitute the operator's experience.
Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease characterized by a high rate of spontaneous mutations involving at least two loci: TSC(1) (9q34) and TSC(2) (16p13). It results in hamartomas or tumours which can affect a variety of organs, most commonly the brain, skin and kidneys. At least half of patients with TSC have underlying renal pathology, most commonly angiomyolipomas (AML) and/or cysts with, more rarely, adenocarcinoma, but oncocytomas, sarcomas, interstitial fibrosis and glomerulosclerosis have all been reported. Renal disorders may be asymptomatic or associated with acute lumbar ache, hematuria, abdominal mass, retroperitoneal hemorrhage. Renal failure is infrequent. The diagnosis of this disease is often performed, as in the present cases, very late and it is made possible by radiological examinations such as TC scan o RMI (when renal failure is present), usually performed after macrohaematuria or abdominal or renal colics or renal failure. When fatty tissue cannot be demonstrated within renal lesion (as in the female case), biopsy can be undertaken to exclude malignancy. Histology at the edge of an AML may look like renal carcinoma, but recent studies suggest that it can be differentiated by staining for HMB-45 which is positive in AML and negative in carcinoma. Two cases of tuberous sclerosis with different neurological fenotype, with bilateral renal angiomyolipomatosis and heavy renal failure, are presented.
A number of proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, protein farnesyltransferase (PFTase) and protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and protein prenylation in cancer cells. In the present study, we evaluated the effect of S(-) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to protein prenylation. S(-) PA (1-3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S(-) PA on SMC and confirmed a block of the cell cycle progression in G(0)/G(1) phase. The antiproliferative effect of S(-) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S(-) PA (1-3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular proteins. We provide evidence that S(-) PA affects protein prenylation, an effect that may contribute to its inhibition of SMC proliferation.
Integrin adhesion receptors transduce signals that control complex cell functions which require the regulation of gene expression, such as proliferation, differentiation and survival. Their intracellular domain has no catalytic function, indicating that interaction with other transducing molecules is crucial for integrin-mediated signalling. Here we have identified a protein that interacts with the cytoplasmic domain of the beta2 subunit of the alphaL/beta2 integrin LFA-1. This protein is JAB1 (Jun activation domain-binding protein 1), a coactivator of the c-Jun transcription factor. We found that JAB1 is present both in the nucleus and in the cytoplasm of cells and that a fraction of JAB1 colocalizes with LFA-1 at the cell membrane. LFA-1 engagement is followed by an increase of the nuclear pool of JAB1, paralleled by enhanced binding of c-Jun-containing AP-1 complexes to their DNA consensus site and increased transactivation of an AP-1-dependent promoter. We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization. This represents a new pathway for integrin-dependent modulation of gene expression.
Experimental electromyogram (EMG) data from the human biceps brachii were simulated using the model described in [10] of this work. A multichannel linear electrode array, spanning the length of the biceps, was used to detect monopolar and bipolar signals, from which double differential signals were computed, during either voluntary or electrically elicited isometric contractions. For relatively low-level voluntary contractions (10%-30% of maximum force) individual firings of three to four-different motor units were identified and their waveforms were closely approximated by the model. Motor unit parameters such as depth, size, fiber orientation and length, location of innervation and tendonous zones, propagation velocity, and source width were estimated using the model. Two applications of the model are described. The first analyzes the effects of electrode rotation with respect to the muscle fiber direction and shows the possibility of conduction velocity (CV) over- and under-estimation. The second focuses on the myoelectric manifestations of fatigue during a sustained electrically elicited contraction and the interrelationship between muscle fiber CV, spectral and amplitude variables, and the length of the depolarization zone. It is concluded that a) surface EMG detection using an electrode array, when combined with a model of signal propagation, provides a useful method for understanding the physiological and anatomical determinants of EMG waveform characteristics and b) the model provides a way for the interpretation of fatigue plots.
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The transfusion records of 341 orthopedic patients who donated blood preoperatively in the years 1992 and 1993 were audited to review the transfusion practices associated with the surgical procedures. The study sample underwent 182 total knee (TKA), 123 total hip (THA) arthroplasties, and 33 laminectomies with fusion (LAM) and 3 without. Data used were age, gender, predonation hemoglobin concentration (Hbd), initial (Hbi) and final (Hbf) hemoglobin concentration, surgical procedure, surgical blood order (SBO), and estimated blood loss (EBL). We analyzed for means and associations and differences between covariates. The means of EBL (mL), transfused units, donated units, Hbi, (g/dL), Hbd, and Hbf (g/dL) for the most common procedures were: TKA--272, 1.1, 2.1, 10.4, 13.9, and 10.1; THA--951, 2.3, 2.4, 9.4, 13.8, and 9.9; and LAM--589, 1.5, 2.2, 12.0, 14.6, and 11.2. Phlebotomies for procedures with minimal blood loss, as for total knee arthroplasties, result in wastage. Autodonation under such circumstances takes patients to an unnecessary low hemoglobin concentration prior to either retransfusing the blood taken or discarding part of it. The number of preoperative autologous units donated can be reduced if predonation hemoglobin concentration is > 15 g/dL and expected blood loss is not > 2 g.
The role of mevalonic acid (MVA) and its products (isoprenoids) in cell proliferation prompted us to investigate the effect of drugs affecting diverse enzymatic steps of the MVA pathway on rat aorta smooth muscle cell (SMC) proliferation. Competitive inhibitors of HMG-CoA reductase (statins) decreased SMC proliferation in a dose-dependent manner. The inhibitory effect induced by simvastatin 3.5 microM (70% +/- 3.8 decrease) was prevented by addition of 100 microM MVA, (100% +/- 2.3), 10 microM farnesol (F-OH) (85% +/- 1.2) and 5 microM of all-trans geranylgeraniol (GG-OH) (precursor of prenylated proteins) (81% +/- 1.1), but not by 2-cis GG-OH (precursor of dolichols), squalene and ubiquinone. The same inhibitory effect was obtained with 6-fluoromevalonate (1-50 microM), an inhibitor of MVA-PP decarboxylase. Squalestatin 1 (1-25 microM) and NB-598 (1-10 microM), potent squalene synthase and epoxidase inhibitors, respectively, caused a complete inhibition of cholesterol synthesis without affecting SMC proliferation. Finally, BZA-5B (10-50 microM) a specific inhibitor of protein farnesyl tranferase (PFTase), inhibited SMC proliferation in a dose- (10-50 microM) and time-dependent manner, reaching 52% +/- 6.3 inhibition after 9 days, in the presence of 50 microM BZA-5B, without affecting cholesterol synthesis. This effect was partially prevented by mevalonate (76% +/- 3.2) and GG-OH (87% +/- 7.3) but not by F-OH. On the other hand, SMC proliferation was not affected by the closely related compound BZA-7B (93% +/- 4), which does not inhibit PFTase. Taken together, these findings support the involvement of specific isoprenoid metabolites, probably through farnesylated and geranylgeranylated proteins in cell proliferation.
We examined the biological fate of 7S globulin from soybean in a hepatoma cell line (Hep G2) and in human skin fibroblasts (HSF) to gain new insights into the 7S globulin cell process, the final effect of which is an enhanced expression of the LDL-receptor. The ability of 7S globulin to bind and to be internalized and degraded by both cell types was investigated under different experimental conditions. In all cases, specific uptake (binding + internalization) and degradation of 125I-7S globulin were curvilinear functions of substrate concentration at 37 degrees C. The two processes were saturated at around 80 mg/L, a concentration at which an up-regulation of LDL-receptor was previously reported. The specific uptake of 125I-7S globulin at 37 degrees C was a curvilinear function of time, and achieved equilibrium after 6 and 12 h in HSF and Hep G2 cells, respectively. Binding experiments, conducted at 4 degrees C in Hep G2 cells, showed a specific and saturable association of 7S globulin to the cell membrane. Linear Scatchard analysis demonstrated a single population of binding sites. The amount of 7S globulin bound at saturation (Bmax) was about 2.73 mg/L, with an apparent Kd of 21 micromol/L, assuming 175 kDa as the 7S globulin molecular weight. SDS-PAGE of Hep G2 membrane proteins incubated with 125I-7S globulin revealed a specific interaction of 7S globulin with a cell protein component with molecular weight between 14 and 21 kDa. Further studies are needed to ascertain whether this interaction is directly or indirectly related to the observed stimulation of the LDL-receptor.
The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by investigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin inhibited the rate of growth of human bronchial smooth muscle cells in a concentration-dependent manner, with an IC50 value of 0.97 +/- 0.1 microM. Mevalonate (100 microM), as well as geranylgeraniol (5 microM), at their highest non-toxic concentrations, restored cell proliferation to control levels.
This report takes into consideration the complications due to "body packers" cocaine absorption. In particular we report a clinical case in which severe dysrhythmias occurred. We think an early insertion of a pacemaker able to rid ectopic focus by overdriving is essential by comparison with an effective anti-dysrhythmic therapy. We also examine the cocaine metabolites values in the patient's serum and urine.
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In order to assess if acute ischemia induces ventricular late potentials (VLP), we have studied 35 patients during coronary angioplasty (PTCA), 15 (Group A) with previous myocardial infarction, 20 (Group B) without. VLP detection was performed by standard technique (in the time domain, with Simson algorithm, on 200 beats, using a 25 Hz filter) before, during and 24 hours after PTCA. This procedure was performed on: anterior descending artery (19 cases), circumflex artery (9 cases), right coronary artery (11 cases); four patients had PTCA on two vessels; in Group A patients, PTCA was performed in vessels related to the previous myocardial infarction. VLP were defined as present when at least two of three standard criteria of positivity were detected (QRSD > 115 ms, RMS40 < 25 microV, LPD > 32 ms). In all patients also left ventricular ejection fraction, end diastolic pressure, regional kinesis and amount of myocardium at risk (as measured by the "Duke University jeopardy score") had been assessed. Furthermore, the total and mean inflation time and the degree of induced acute ischemia were also considered. The following results were obtained: no patient had VLP at basal conditions, during PTCA in all patients of both groups we observed a significant prolongation of QRSD but only Group A patients developed VLP, in 56% of cases versus none of Group B. This event was transient: in fact, 24 hours after the procedure VLP were no more present. The two groups did not differ as regards to the values of all the other anatomic and functional above mentioned parameters. Probably the acute ischemia cannot evocate VLP by itself, but this "trigger" needs also a particular substrate with anatomical and functional abnormalities due to a previous myocardial infarction. Further investigations and long follow-up studies are requested to assess if these data could account for the presence of ventricular tachyarrhythmias in patients with acute coronary ischemia and previous myocardial infarction.
27-Hydroxycholesterol**, 25-hydroxycholesterol and cholesterol suppressed LDL uptake and degradation in human extrahepatic and hepatic cell lines in a concentration-dependent manner. Cholesterol was the least potent, and the inhibitory effect of oxysterols was more pronounced in skin fibroblasts and in endothelial cell line EAhy 926 than in hepatoma HepG2 cells. Shorter incubations were required for oxysterols to achieve 50% inhibition of LDL uptake and degradation in all cultured cells. The inhibition of LDL catabolism in extrahepatic cells by 27-hydroxycholesterol occurred at concentrations close to those observed in human plasma (0.2-0.6 microM). The results support a possible role of 27-hydroxycholesterol, a physiological oxysterol, in the regulation of cellular cholesterol homeostasis in non-hepatic tissues.
It has been observed that the pineal gland seems to modulate diencephalic neuroendocrine activity through its principal hormone, melatonin. In animals, melatonin inhibits the secretion and release of hypophyseal gonadotropins, probably by inhibiting hypothalamic releasing factors; in man, on the contrary, the administration of LHRH seems to have a stimulating effect on melatonin serum levels. In the light of this, in pathologies characterised by an imbalance in the hypothalamus-hypophyseal-gonad axis, it is possible to hypothesise variations in the secretion of melatonin and/or in its circadian fluctuations. In order to clarify further the relationship between the epiphysis and the hypothalamus-hypophyseal axis, the present study evaluated the pattern of melatonin secretion in a group of 16 patients with Klinefelter's syndrome. The circadian rhythm of melatonin secretion was determined from venous blood samples taken at 9 am, 1 pm, 5 pm, 9 pm, 1 am and 5 am; the same protocol was also followed in two control groups of respectively prepuberal and puberal healthy subjects. During the night samples were taken as rapidly as possible, using a red light source in order to not interfere with melatonin secretion. All of the examinations were performed during the winter period. Serum levels of melatonin were determined, after extractions with diethylether, by means of a double antibody RIA using commercially available kits (Bioscience Product--The Netherlands). Intra- and inter-assay coefficients of variation were respectively 3% and 8%. The data are reported as mean values +/- SD; the results were analysed by means of Student's test for unpaired data and analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)