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Biomedical subjects

L Tonelli

Publications and source records attributed to L Tonelli.

At least 19 recordsLinked to original sources

Dyspnoea and hypoxaemia after lung surgery: the role of interatrial right-to-left shunt.

After lung surgery, some patients complain of unexplained increased dyspnoea associated with hypoxaemia. This clinical presentation may be due to an interatrial right-to-left shunt despite normal right heart pressure. Some of these patients show postural dependency of hypoxaemia, whereas others do not. In this article, the pathogenesis and mechanisms involved in this post-surgical complication are discussed, and the techniques used for confirmation and localisation of shunt are reported. An invasive technique, such as right heart catheterisation with angiography, was often used in the past as the diagnostic procedure for the visualisation of interatrial shunt. As to noninvasive techniques, a perfusion lung scan may be used as the first approach as it may detect the effect of the right-to-left shunt by visualising an extrapulmonary distribution of the radioactive tracer. The 100% oxygen breathing test could also be used to quantify the amount of right-to-left shunt. Particular emphasis is given to newer imaging modalities, such as transoesophageal echocardiography, which is minimally invasive but highly sensitive in clearly visualising the atrial septum anatomy. Finally, the approach to closure of the foramen ovale or atrial septal defect is discussed. Open thoracotomy was the traditional approach in the past. Percutaneous closure has now become the most used and effective technique for the repair of the interatrial anatomical malformation.

Aged↗

Lipopolysaccharide-induced oestrogen receptor regulation in the paraventricular hypothalamic nucleus of lewis and Fischer rats.

Oestrogen receptor (ER) regulation of gene transcription in neurosecretory and pituitary cells has been proposed as an important mechanism for increased hypothalamic-pituitary-adrenal (HPA) axis responses in females of several mammalian species, including humans. Inbred female Fischer (F344/N) and Lewis (LEW/N) rats have similar oestrogen levels, although Fischer rats exhibit hyper- and Lewis rats hypo-HPA axis responses. The blunted HPA axis response of Lewis rats has been associated with their blunted hypothalamic corticotropin releasing hormone (CRH) expression. To determine if the female CRH expression deficiency in Lewis rats is associated with defective ER expression and regulation, hypothalamic paraventricular nucleus (PVN) transcript levels of CRH and ER were determined under basal conditions and after immune challenge. Microdissected PVN were obtained from control and lipopolysaccharide (LPS) treated Lewis and Fischer rats and CRH, ERalpha and beta mRNA levels were determined by semiquantitative reverse-transcriptase-polymerase chain reaction. In addition, ERalpha and beta protein levels were determined by semiquantitative Western blots. ERalpha and beta mRNA and protein levels in the PVN of control Fischer rats were significantly higher than in control Lewis rats. ERalpha and beta mRNA and protein levels in Fischer rats were reduced by LPS administration at the time of maximal CRH mRNA levels but did not change in Lewis rats, an effect independent of oestrogen levels. These data indicate that defective neuroendocrine HPA axis responses are associated with defective ER expression and regulation in Lewis PVN despite oestrogen concentrations.

Animals↗

Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients.

PURPOSE: Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE. SUBJECTS AND METHODS: We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE. RESULTS: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively. CONCLUSIONS: In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.

Adolescent↗

Effects of cross fostering on open-field behavior, acoustic startle, lipopolysaccharide-induced corticosterone release, and body weight in Lewis and Fischer rats.

Lewis (LEW/N) and Fischer (F344/N) rats differ on a myriad of behavioral and physiological endpoints, some of which have been reported to be affected by maternal experience in outbred rats and other strains. To assess whether epigenetic factors contribute to the differential behavioral responses to stress and pro-inflammatory challenges in these strains, the effects of cross fostering on open-field, acoustic startle, and glucocorticoid reactivity to lipopolysaccharide (LPS) were examined in the present experiment. In the open-field test, although in-fostered female LEW/N and F344/N strains did not differ, female LEW/N rats displayed significantly greater activity than female F344/N rats in the cross-fostered condition. Differences between males of the two strains were increased by cross fostering, with the LEW/N strain displaying greater total activity. In acoustic startle, there was little strain difference between in-fostered or cross-fostered female rats. On the other hand, in-fostered male LEW/N rats had a significantly greater startle response than in-fostered male F344/N rats, an effect that was dramatically reduced by cross fostering. In-fostered female LEW/N rats displayed a blunted corticosterone response relative to in-fostered female F344/N rats, an effect that was reduced by cross fostering. Conversely, although there was no strain difference between male in-fostered rats, cross-fostered male F344/N rats displayed a significantly greater corticosterone response to LPS than cross-fostered male LEW/N rats. Finally, body weight differences between in-fostered LEW/N and F344/N rats were reduced by cross fostering. Together, these data illustrate that maternal factors play a role in the behavioral and physiological responses to stress between the two strains.

Animals↗

Neuroendocrine responses regulating susceptibility and resistance to autoimmune/inflammatory disease in inbred rat strains.

Rodent animal models of inflammatory and autoimmune disease have been important tools in the study of the interaction between neuroendocrine physiology and the immune responses. The rat has been particularly useful in part because, in contrast to other species, most rat models of autoimmune/inflammatory disease are induced rather than spontaneous. This allows for systematic and controlled manipulations of the neuroendocrine system in relation to exposure to the antigen or proinflammatory trigger. The most frequently used immune challenges include lipopolysaccharide-induced septic shock, carrageenan-induced local inflammation and adjuvant or bacterial cell wall-induced arthritis. By analyzing the responses to these challenges in different strains of rats and mice it has been possible to define the relationships between the neuroendocrine and immune systems and to identify some mechanisms through which these connections confer susceptibility and resistance to autoimmune and inflammatory diseases. The present review will discuss data obtained from rodent physiology, indicating that an important component in the susceptibility or resistance to development of these diseases is due to dysfunctional regulation of the immune response by the neuroendocrine hypothalamic-pituitary-adrenal axis. In particular, the importance of neurons of the paraventricular hypothalamic nucleus in determining susceptibility or resistance to autoimmune and inflammatory disease will be discussed.

Animals↗

Gerbil angiotensin II AT1 receptors are highly expressed in the hippocampus and cerebral cortex during postnatal development.

Increasing evidence suggests that Angiotensin II, classically known from its many effects regulating salt and water homeostasis, is also involved in brain development and cognitive functions through activation of AT1 Angiotensin II receptors. The recently cloned gerbil AT1 receptor is expressed in brain areas controlling hydro-mineral homeostasis, and particularly highly expressed in limbic areas such as the hippocampal formation. We quantified the gerbil AT1 receptor messenger RNA expression and receptor binding by quantitative in situ hybridization and receptor autoradiography, respectively, in the hippocampal formation and cerebral cortex of gerbils during postnatal development. The receptor messenger RNA and binding were present from birth and showed a gradual and sustained increase through postnatal maturation in the CA1 and CA2 regions of the hippocampus and in the dentate gyrus. Conversely, in the CA3 region, no binding was detected while receptor messenger RNA peaked at 15 days after birth and disappeared in the adult. The highest receptor messenger RNA expression and binding were found in the septomedial portions of the CA1 region and at septal levels of the CA2 region. We detected the highest receptor messenger RNA expression at postnatal day one in the frontolateral pole of the cerebral hemispheres. In these areas, and in the frontoparietal and insular cortex, receptor messenger RNA dramatically decreased during postnatal life. Similarly, we found receptor messenger RNA expression in the cingulate, retrosplenial, perirhinal and infralimbic cortex with higher values during the first two weeks of development and decreased expression in the adult. However, receptor binding in the cerebral cortex, did not decrease during postnatal life. The differential profile of receptor messenger RNA expression and binding in the gerbil cortex and hippocampus during postnatal maturation suggest a role for AT1 receptors in the development and function of the corticohippocampal system.

Aging↗

Accuracy of clinical assessment in the diagnosis of pulmonary embolism.

To provide clinical diagnostic criteria for pulmonary embolism (PE), we evaluated 750 consecutive patients with suspected PE who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Prior to perfusion lung scanning, patients were examined independently by six pulmonologists according to a standardized diagnostic protocol. Study design required pulmonary angiography in all patients with abnormal scans. Patients are reported as two distinct groups: a first group of 500, whose data were analyzed to derive a clinical diagnostic algorithm for PE, and a second group of 250 in whom the diagnostic algorithm was validated. PE was diagnosed by angiography in 202 (40%) of the 500 patients in the first group. A diagnostic algorithm was developed that includes the identification of three symptoms (sudden onset dyspnea, chest pain, and fainting) and their association with one or more of the following abnormalities: electrocardiographic signs of right ventricular overload, radiographic signs of oligemia, amputation of hilar artery, and pulmonary consolidations compatible with infarction. The above three symptoms (singly or in some combination) were associated with at least one of the above electrocardiographic and radiographic abnormalities in 164 (81%) of 202 patients with confirmed PE and in only 22 (7%) of 298 patients without PE. The rate of correct clinical classification was 88% (440/500). In the validation group of 250 patients the prevalence of PE was 42% (104/250). In this group, the sensitivity and specificity of the clinical diagnostic algorithm for PE were 84% (95% CI: 77 to 91%) and 95% (95% CI: 91 to 99%), respectively. The rate of correct clinical classification was 90% (225/250). Combining clinical estimates of PE, derived from the diagnostic algorithm, with independent interpretation of perfusion lung scans helps restrict the need for angiography to a minority of patients with suspected PE.

Adolescent↗

Diagnostic value of gas exchange tests in patients with clinical suspicion of pulmonary embolism.

OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal scans who had normal P(A-a)O2, PaO2 and PaCO2 were 20, 25 and 37%, respectively. No differences were observed in the mean values of arterial blood gas data between patients with pulmonary embolism and those who had abnormal scans and negative angiograms. Among the 773 patients with suspected pulmonary embolism, 364 (47%) had prior cardiopulmonary disease. Pulmonary embolism was diagnosed in 151 (41%) of 364 patients with prior cardiopulmonary disease, and in 161 (39%) of 409 patients without prior cardiopulmonary disease. Among patients with pulmonary embolism, there was no difference in arterial blood gas data between patients with and those without prior CPD. CONCLUSION: These data indicate that arterial blood gas tests are of limited value in the diagnostic work-up of pulmonary embolism if they are not interpreted in conjunction with clinical and other laboratory tests.

Journal Article↗

Non-invasive diagnosis of pulmonary embolism.

Pulmonary embolism (PE) remains a challenging diagnostic problem because it mimics other cardiopulmonary disorders. Pulmonary angiography is still the reference standard for diagnosing PE but it is costly, invasive and not readily available. Non-invasive diagnostic strategies have therefore been developed to forego pulmonary angiography in patients suspected of having PE. Ventilation/perfusion lung scanning is, at present, the most widely used non-invasive diagnostic test for PE. A high probability ventilation/perfusion scan (segmental or greater perfusion defects with normal ventilation) warrants the institution of anticoagulant therapy especially when paired with high clinical suspicion of PE. Yet, only a minority of patients with confirmed PE have high probability ventilation/perfusion scans. Ventilation/perfusion abnormalities other than those of the high probability scan should be regarded as non-diagnostic. Under these circumstances, documentation of deep vein thrombosis by non-invasive leg testing warrants anticoagulation without the need for angiography. However, a single negative venous study result does not permit to rule out PE in patients with non-diagnostic ventilation/perfusion scans. Results of a recent prospective study indicate that accurate diagnosis or exclusion of PE is possible with perfusion lung scanning alone (without ventilation imaging). Combining perfusion lung scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected PE.

Clinical Trials as Topic↗

Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED).

To assess the value of perfusion lung scan in the diagnosis of pulmonary embolism, we prospectively evaluated 890 consecutive patients with suspected pulmonary embolism. Prior to lung scanning, each patient was assigned a clinical probability of pulmonary embolism (very likely, possible, unlikely). Perfusion scans were independently classified as follows: (1) normal, (2) near-normal, (3) abnormal compatible with pulmonary embolism (PE+: single or multiple wedge-shaped perfusion defects), or (4) abnormal not compatible with pulmonary embolism (PE-: perfusion defects other than wedge-shaped). The study design required pulmonary angiography and clinical and scintigraphic follow-up in all patients with abnormal scans. Of 890 scans, 220 were classified as normal/or near-normal and 670 as abnormal. A definitive diagnosis was established in 563 (84%) patients with abnormal scans. The overall prevalence of pulmonary embolism was 39%. Most patients with angiographically proven pulmonary embolism had PE+ scans (sensitivity: 92%). Conversely, most patients without emboli on angiography had PE- scans (specificity: 87%). A PE+ scan associated with a very likely or possible clinical presentation of pulmonary embolism had positive predictive values of 99 and 92%, respectively. A PE- scan paired with an unlikely clinical presentation had a negative predictive value of 97%. Clinical assessment combined with perfusion-scan evaluation established or excluded pulmonary embolism in the majority of patients with abnormal scans. Our data indicate that accurate diagnosis of pulmonary embolism is possible by perfusion scanning alone, without ventilation imaging. Combining perfusion scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected pulmonary embolism.

Adolescent↗

Sodium depletion induces Fos immunoreactivity in circumventricular organs of the lamina terminalis.

Acute sodium depletion by peritoneal dialysis (PD) induces c-fos expression in the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), in conscious rats. Fos immunoreactive (Fos-ir) neurons detected by immunohistochemistry first appeared in these nuclei 60 min after PD, increased gradually in the next 4 h and remained high for 27 h following PD. Fos-ir cells were distributed throughout the body of SFO, being the core of the posterior sections preferentially activated, whereas Fos-ir neurons occurred around the periphery of OVLT (annular disposition). When rats were allowed to drink sodium salt (1.8% NaCl) 24 h after PD, there was a marked reversion of the c-fos expression in the OVLT and a comparatively smaller effect in the SFO. Intracerebroventricular infusion of hypertonic CSF (170 mM NaCl) from 30 min before and during 4 h after PD, significantly inhibited the c-fos expression in both nuclei. These results demonstrate that an acute body sodium deficit induces c-fos activity in SFO and OVLT neurons, indicating the special role of these structures in sodium balance regulation. They also show that the sodium-depletion-induced production of Fos in neurons of the lamina terminalis can be modulated by central or systemic reposition of sodium.

Analysis of Variance↗

Dopaminergic neurons in the zona incerta modulates ingestive behavior in rats.

The zona incerta, located in the ventral thalamus, is a site of convergence of signals related to drinking. In the present experiments, agonists and antagonists of dopamine receptors were injected into the ZI of animals deprived of water overnight. Injection of 53 nM dopamine or the D2 dopamine receptor agonist PPHT caused a reduction of water and food intake, while the injection of the D1 receptor agonist SKF38393 had no effect. The current results suggest that dopamine injected into the ZI exerts inhibitory influences on drinking behavior mediated by D2 type receptor.

Animals↗

Enhancement of water intake in rats after lidocaine injection in the zona incerta.

Physiological evidence indicates that the zona incerta (ZI) may be an important region for convergence of signals mediating drinking. It is known that the ZI receives neural influences from brain osmoreceptive zones. Also there are wide-spread projections from the ZI to the neocortex. In the present experiments, lidocaine (1 microliter, 20 ng/microliters) was injected into the rostral aspect of the ZI. The animals were previously stimulated for water drinking by: a) overnight water deprivation; b) 2 M NaCl IP; c) AII (50 ng) in the anteroventral wall of the third ventricle (AV3V). In every case, lidocaine administration significantly enhanced the volume of water drank. The results support the idea that ZI exerts an inhibitory influence upon the expression of drinking behavior.

Angiotensin II↗

[Monitoring of intracranial pressure].

A very small fiberoptic catheter initially developed as an intravascular pressure sensor was incorporated into a system to be used as an intracranial pressure (ICP) monitor. 13 patients with intracranial hypertension have been studied with this probe. The clinical experience confirmed the safety, accuracy and reliability of the device. The monitor has functioned very well, and there have been no complications except for two breakages of optic fiber as a result of nursing manoeuvres. This new device can be placed into the ventricular, subdural and epidural space. Camino System appears to offer advantages over other monitors presently in use.

Adult↗

Investigation on cerebrospinal fluid opioids and neurotransmitters related to spinal cord stimulation.

The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, beta-endorphin, beta-lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50% increase of cerebrospinal beta-endorphin and beta-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-endorphin response to SCS could have clinical value in predicting the success of treatment.

Adult↗

Billroth I versus Billroth II partial gastrectomy in the treatment of gastric ulcer.

Short- and long-term results of B-I and B-II reconstructions were compared in order to assess which anastomosis is to be recommended after partial gastrectomy for gastric ulcer. All the patients (287) electively operated for gastric ulcer 10-20 years ago were considered for the study. Operative mortality did not significantly differ, while duration of post-operative time before discharge and post-operative morbidity were significantly lower after B-I. Long-term percentage probability of survival was higher after B-I than after B-II (87.0 and 63.7 after 19 years, respectively), while quality of life was similar in the two groups. In the 64 subjects (26 B-I and 38 B-II) who underwent the study protocol, fasting bile reflux appeared more abundant and bile acid concentration greater after B-II than after B-I. While bacteria and nitrite concentrations did not differ in the two groups, bile acid pattern differed in a greater deoxycholic acid percentage concentration in the B-II group. In spite of an increased deoxycholic acid concentration and therefore a probably more lithogenic bile, gallstones were shown in 23.11% and 39.41% of the B-I and the B-II subjects, respectively, without significant differences. In conclusion, when partial gastrectomy is indicated for gastric ulcer, B-I reconstruction seems preferable to B-II because of its lower post-operative mobility, less evident entero-gastric reflux and histological consequences, less evident bile acid pattern changes from normal, and an apparently longer life-expectancy after discharge.

Adult↗

Gastric histology and fasting bile reflux after partial gastrectomy.

Forty-four randomized, partially gastrectomized subjects were studied to assess whether gastric histologic findings after partial gastrectomy were related to reflux. Gastric biopsy specimens (12) were taken at different distances from the anastomosis. Histologic findings were as follows: (a) hyperplastic changes of the foveolar epithelium and (b) loss of the chief and parietal gland cells with atrophy of gastric glands (chronic atrophic gastritis). Hyperplastic changes typical of the perianastomotic area gradually decreased with increasing distance from the anastomosis. Hyperplastic changes showed a greater prevalence in Billroth II than in Billroth I subjects (100% vs. 29.4%). No significant association was found between histologic findings and symptoms. Hourly bile acid quantity (fasting bile reflux) and concentration were determined in the gastric aspirates. Bile reflux was greater after Billroth II than after Billroth I (fasting bile reflux median values: 30.5 vs. 0.18 mumol/h, respectively). The same was true for bile acid concentration (mean bile acid concentration median values: 624.9 vs. 17.5 mumol/L, respectively). Moreover, Billroth I subjects with hyperplasia had a greater quantity and concentration of reflux than those without hyperplasia (fasting bile reflux and mean bile acid concentration median values: 2.6 vs. 0.8 mumol/h and 4.7 vs. 2.7 mumol/L, respectively). These findings show that bile reflux is correlated with hyperplastic changes of the foveolar epithelium, but prevalence and severity of atrophic gastritis were not related to reflux. Therefore, although we failed to show any relationship between chronic atrophic gastritis and reflux, foveolar hyperplasia was shown to be reflux related.

Bile Reflux↗