Physical Mechanisms Providing Clinical Information From Ultrasound Lung Images: Hypotheses and Early Confirmations.

In standard B mode imaging, a set of ultrasound pulses is used to reconstruct a 2-D image even though some of the assumptions needed to do this are not fully satisfied. For this reason, ultrasound medical images show numerous artifacts which physicians recognize and evaluate as part of their diagnosis since even one artifact can provide clinical information. Understanding the physical mechanisms at the basis of the formation of an artifact is important to identify the physiopathological state of the biological medium which generated the artifact. Ultrasound lung images are a significant example of this challenge since everything that is represented beyond the thickness of the chest wall ( ≈ 2 cm) is artifactual information. A convincing physical explanation of the genesis of important ultrasound lung artifacts does not exist yet. Physicians simply base their diagnosis on a correlation observed over the years between the manifestation of some artifacts and the occurrence of particular lung pathologies. In this article, a plausible genesis of some important lung artifacts is suggested.

Lung and ultrasound: time to "reflect".

BACKGROUND: Literature concerning lung ultrasonography is largely growing and opening new diagnostic opportunities. The clinical value of the ultrasonographic interstitio-alveolar syndrome, based on artifactual (lung comets or B-lines) rather than real images, in the detection of lung contusion, pneumonia and pulmonary edema, is clearly demonstrated. As clinical echographists, though, we are living the paradox of relying our experience in lung pathology on images whose biophysical and genetic nature is not fully understood. OBJECTIVE AND PERSPECTIVES: A detailed review of the ultimate findings with an analysis of recent and past literature regarding the formation of ultrasonographic artifacts was undertaken with the aim of clarifying what we know and where we are heading in this field. It is important for us to underline how lung ultrasonography is not morphological, as this, along with the study of artifact formation, will be the base for the development of a novel 'view' able to take us from artifact to reality in terms of 'quantification' of lung disease and damage. CONCLUSIONS: Lung ultrasonographic artifacts need to be read in a new light which will privilege biophysical knowledge and research. In this field a gap of basic knowledge clearly exists. A greater understanding of the formation of acoustic artifacts from ultrasound interference on discretely aerated tissues of variable density, would place the practice of lung "ultrasonography" in the correct technological and clinical position.

Bedside lung ultrasound in critical care practice.

Ultrasonographic scanning of the lung is gaining ever-growing recognition as a diagnostic and monitoring imaging technique. Its role in trauma assessment has already been established as an extension of the focused assessment of trauma with sonography for the diagnosis of pneumothorax. As more centers are discovering the advantages of ultrasound and conducting experimental and comparative studies, its use for diagnosing many other lung pathologies is becoming even more important. In-depth studies and innovative ideas are needed to explore the possibilities of this technology. We believe that, ultimately, the advantages for the patient will far outweigh the disadvantages of ultrasonography. Here, we review all possible applications of lung ultrasonography used thus far in Intensive Care Units, where a readily available and biologically non-invasive imaging technique may make the difference in diagnosis. In addition, we describe how the non-invasive nature of ultrasonography allows it to be used as a monitoring device of disease progression vs the healing process. We also provide a detailed explanation of the methods and materials necessary and a few indications towards unanswered questions in this field of research.

Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides.

BACKGROUND: Acute dyspnoea as a presenting symptom is a frequent diagnostic challenge for physicians. The main differential diagnosis is between dyspnoea of cardiac and non-cardiac origin. Natriuretic peptides have been shown to be useful in this setting. Ultrasound lung comets (ULCs) are a simple, echographic method which can be used to assess pulmonary congestion. AIM: To evaluate the accuracy of ULCs for predicting dyspnoea of cardiac origin compared to natriuretic peptides. METHODS: We evaluated 149 patients admitted with acute dyspnoea. Chest sonography and NT-proBNP assessments were performed a maximum of 4 h apart and independently analyzed. ULCs were evaluated via cardiac probes placed on the anterior and lateral chest. Two independent physicians, blinded to ULCs and NT-proBNP findings, reviewed all the medical records to establish the aetiologic diagnosis of dyspnoea. RESULTS: Cardiogenic dyspnoea was confirmed in 122 patients and ruled-out in 27 patients. The number of ULCs was significantly correlated to NT-proBNP values (r=.69, p<.0001). Receiver operating characteristic analysis, showed an area under the curve of .893 for ULCs and .978 (p=.001) for NT-proBNP, in predicting the cardiac origin of dyspnoea. CONCLUSIONS: In patients admitted with acute dyspnoea, pulmonary congestion, sonographically imaged as ULCs, is significantly correlated to NT-proBNP values. The accuracy of ULCs in predicting the cardiac origin of dyspnoea is high.

Sonographic findings in pulmonary diseases.

Lung sonography, generally not thought to be diagnostic, is currently being reconsidered and is developing into an interesting clinical possibility. The principal sonographic signs of lung disease are described in light of our personal experience and the current literature.

Clinical and pathological characterisation of primary pulmonary hypertension in a dog.

Primary pulmonary hypertension was diagnosed in an eight-year-old labrador retriever on the basis of echocardiographic findings of severe right ventricular eccentric hypertrophy, abnormally high systolic and diastolic pulmonary arterial pressures calculated by applying the modified Bernoulli equation to the tricuspid and pulmonary insufficiency peak velocities, and the absence of any underlying disease known to cause secondary pulmonary hypertension. The clinical abnormalities developed gradually, from exercise intolerance starting early in life to terminal right-sided congestive heart failure. Consistent histopathological findings were severe intimal and medial thickening of small arteries and arterioles that led to vascular obliteration.

Detection of mycobacteria and chlamydiae in granulomatous inflammation of reptiles: a retrospective study.

A retrospective study on reptile tissues presenting with granulomatous inflammation was performed to detect the possible presence of mycobacteria and chlamydiae in these lesions. Ninety cases including 48 snakes, 27 chelonians, and 15 lizards were selected. Mycobacteria were detected by Ziehl-Neelsen (ZN) staining and a broad-range polymerase chain reaction (PCR) followed by DNA sequencing. To detect chlamydiae, immunohistochemistry with monoclonal antibodies against chlamydial lipopolysaccharide (LPS) and a Chlamydiales order-specific PCR and sequencing were applied. Acid-fast bacilli were found in 14 cases (15.6%) by ZN staining and in 23 cases (25.6%) by PCR. Sequence analysis revealed the presence of Mycobacteria other than Mycobacterium tuberculosis complex (MOTT). Chlamydial LPS antigen was observed within granulomas from five samples (5.6%), whereas the PCR screen revealed 58 positive cases (64.4%). Of these, 9 cases (10%) showed 98-99% similarity to Chlamydophila (Cp.) pneumoniae and 49 cases (54.4%) displayed a high similarity (88-97%) to the newly described "Chlamydia-like" microorganisms Parachlamydia acanthamoebae and Simkania negevensis. Results from this study confirm, on the one hand, that MOTT are probably the most important infectious etiology for granulomatous inflammation in reptiles. On the other hand, they indicate that chlamydia infects reptiles and that Cp. pneumoniae should be considered an etiological agent of granulomatous lesions of reptiles. Because both MOTT and Cp. pneumoniae are human pathogens, the potential of zoonotic transmission from reptiles to humans has to be considered. In contrast, the significance of Chlamydia-like isolates remains completely open, and further studies are needed to evaluate their role.

Homocysteine, vitamins and gene mutations in peripheral arterial disease.

A case-control study was undertaken involving 51 consecutive patients with peripheral artery obstructive disease (PAOD) scheduled for angioplasty. Blood samples of these patients were analysed for plasma homocysteine (tHcy) and levels of vitamin B12 and folate, and the MTHFR gene was assessed for mutation. Patients were compared with age- and sex-matched controls who did not present with cardiovascular risk factors. Mean tHcy did not differ between cases and controls (13.3 +/- 5.7 and 12.6 +/- 4.9 micromol/l, P = 0.49). More patients were above the 95th percentile as determined from the data in the control group with an odds ratio (OR) that almost reached statistical significance [OR, 2.8; 95% confidence interval (CI), 0.9-8.7], but on separate analyses only female patients showed higher tHcy than female controls (15.6 versus 12.0 micromol/l, P = 0.05), with an odds ratio for tHcy above the 95th percentile of 10.5 (95% CI, 1.1-96.6). The TT genotype of the MTHFR gene was found in 24% of the patients and in 12% of the controls (OR, 2.3; 95% CI, 0.8-6.7). Our findings point to a modest association between tHcy and PAOD, with a difference between cases and controls restricted to the highest percentile in female patients. A weak but not significant association was also found for the TT genotype of the MTHFR gene.

Preprogramming and control activity of bimanual self-paced motor task in Parkinson's disease.

OBJECTIVE: The authors investigated programming (Bereitschaftspotential or BP) and control activity (Skilled Performance Positivity or SPP) of a bimanual, sequential, skilled motor act in off-therapy Parkinson's disease (PD) patients. METHODS: We recorded Movement Related Potentials (MRPs) in 12, non-demented, off-therapy parkinsonian patients and in 17 control subjects who were performing a skilled, time-locked motor act, which was not routine in their everyday life but had to be learned: the Skilled Performance Task (SPT). BP, SPP and correct performances were evaluated in grand average waveforms and in sequential blocks. RESULTS: The analysis of correct performances showed that accuracy in PD patients was significantly lower than in the control group and this accuracy did not improve throughout the blocks. A significantly low level of performances was associated with an increased BP amplitude (P<0.05) and decreased SPP amplitude (P<0.05) in PD patients. CONCLUSION: Our findings suggest that skill motor learning is impaired in non-demented unmedicated PD patients. We discuss the view that PD patients may allocate more attentional resources, as suggested by the increased BP amplitude, the decreased SPP amplitude and the low correct performances, in order to perform a new skilled motor act.

[Boerhaave syndrome. A case report and review of the literature]. / La sindrome di Boerhaave. Descrizione di un caso e revisione della Letteratura.

Spontaneous esophageal perforation (Boerhaave's syndrome) remains a difficult diagnostic and management problem with controversial recommendations regarding its treatment. The clinical manifestations of the disease are variable, and may be misleading, thus delaying accurate recognition. On the other hand, in view of the rapid onset of severe complications, particularly mediastinitis, a prompt diagnosis is essential to a better prognosis, successful operative outcome and potential survival. A case of spontaneous perforation of the thoracic esophagus penetrating the left pleural space treated within 4 hours from admission to the Emergency Room, with minimal surgical intervention is presented. Despite negative chest X-ray, a thoracic TC showed a small right sided effusion with left sided hydropneumothorax, and the definitive diagnosis was obtained by contrast study with a water soluble medium which showed the leak communicating freely with the left pleural space. The patient underwent repair by thoracic approach, the rupture was closed with a primary suture without flap reinforcement and the pleural space drained with the placement of single chest thoracostomy tube. The recovery was uneventful. The analysis of this case report and of the appropriate literature reveals that a poor prognosis is correlated with the time elapsed between the perforation and treatment. In conclusion the importance of an early aggressive surgical treatment for the Boerhaave's syndrome is emphasized, because any perforation treated more than 24 hours after the onset of symptoms, irrespective of the procedure used, is associated with a significantly higher morbility and mortality.

Flow cytometric detection of p53 protein after incubation of a pre-B cell line with antitumor agents.

BACKGROUND: The study of new substances capable of counteracting tumor development has focused, in recent years, on several of the steps in a cell's initiation of the process of apoptosis. One of the crucial events is the activation of p53, leading to a cell cycle G1/S block or to programmed cell death. METHODS: We report here a parallel flow cytometric method for semiquantitative detection of p53 protein and apoptosis (percent of apoptotic cells) in a pre-B leukemic cell line (NALM-6) exposed to various antitumor agents (2.35 microg/ml etoposide; 0.175 microg/ml FCE296; 0.4 microg/ml FCE624; and 1.5 microg/ml L-PAM). RESULTS: All of the substances proved to be capable of inducing an increase of p53 after 16 or 24 h of incubation. In all experiments with antitumor agents we also found an onset of apoptosis after 24 h of incubation with the substance, as determined by the annexin V flow cytometric assay and by DNA fragmentation. CONCLUSIONS: This technique, based on flow cytometric data of both p53 intracellular content and percentage of apoptotic cells, is suitable to determine the amount of antitumor agent needed to induce p53, and thus to dose the drug in relation to the sensitivity of a defined tumor as well as choose the more efficacious drug, depending on cell responsiveness. The study of antitumor substances that induce apoptosis, bypassing p53, could also be evaluated by this method, in view of the development of substances for the treatment of p53-mutated tumors.

Follicular fluid proteins stimulate nitric oxide (NO) synthesis in human sperm: a possible role for NO in acrosomal reaction.

Nitric oxide (NO) is a free radical involved in the regulation of several functions of the male genitourinary system. It is produced by neurons and the endothelium and epithelia of reproductive system; it mediates penile erection and regulates sperm motility, viability, and metabolism. Here we show that human spermatozoa exhibit a detectable NO synthase (NOS) activity, measured both as ability of the intact sperm and cell lysate to convert L-[3H]arginine into L-[3H]citrulline and as 24 h accumulation of extracellular nitrite in intact sperm suspensions. NOS activity (identified as an endothelial isoform) was inhibited by L-canavanine and N(G)-monomethyl-L-arginine, and nitrite accumulation was inhibited by the NO scavenger hemoglobin; both enzyme activity and nitrite production were increased by a 24 h incubation of spermatozoa with protein-enriched extracts of human follicular fluid (PFF); a significant increase of citrulline synthesis was observed only after a 4 h incubation with 40% PFF, a time period during which acrosomal reactivity was significantly increased. PFF-induced acrosomal reaction was inhibited by L-canavanine and hemoglobin, and the NO donors sodium nitroprusside (SNP), S-nitroso-N-acetyl-penicillamine (SNAP), and DETA NONOate were able to increase the percentage of reacted spermatozoa. Our results suggest that NO synthesized by human sperm may play a role in follicular fluid-induced acrosomal reaction.

Resveratrol arrests the cell division cycle at S/G2 phase transition.

Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring phytoalexin, found in grapes and wine, which has been reported to exert a variety of important pharmacological effects. We have investigated the activity of resveratrol on proliferation and differentiation of the promyelocitic cell line HL-60. A concentration as low as 30 microM causes a complete arrest of proliferation and a rapid induction of differentiation towards a myelo-monocytic phenotype. Analyses by flow cytometry showed the absence of the G2/M peak and the accumulation of cells in G1 and S phases. Moreover, at the concentrations employed, a very low amount of apoptotic cells was evidenced. A detailed biochemical analysis demonstrated that the G1 phase of the cell division cycle engine was completely unmodified by resveratrol addition, thus indicating that the G1 --> S transition occurs normally. Conversely, after only 24 h treatment, a significant increase of cyclins A and E could be observed along with the accumulation of cdc2 in the inactive phosphorylated form. These data demonstrate that resveratrol causes a complete and reversible cell cycle arrest at the S phase checkpoint.

Low dosage clozapine effects on L-dopa induced dyskinesias in parkinsonian patients.

OBJECTIVES: The aim of this study was to investigate the clinical efficacy of clozapine, an atypical neuroleptic, on L-dopa induced dyskinesias of Parkinson's disease. MATERIAL AND METHODS: In an open study, a group of 10 PD patients was treated with low dosage clozapine (mean 30 mg/day) for a 4-month period and L-dopa dyskinesias were evaluated in basal conditions and during clozapine treatment after the usual morning dose of clozapine. We utilized the AIMS for evaluation of dyskinesias and UPDRS for the assessment of motor performances. RESULTS: Clozapine produced a significant (P<0.05) reduction of dyskinesias 1 week after the therapy onset. This effect was more pronounced at the end of the 2nd week and remained stable through the following months. We did not observe significant variations of motor performances. CONCLUSION: A low dose of clozapine appears to be beneficial for patients with L-dopa induced dyskinesias that do not respond to other drugs and therapeutic measures.