Increase in environmental temperature affects exploratory behaviour, anxiety and social preference in Danio rerio.

The aim of this work is to investigate the effect of a temperature increase on the behaviour of adult zebrafish (Danio rerio) maintained for 21 days at 34 °C (treatment) and 26 °C (control). The temperatures chosen are within the vital range of zebrafish and correspond to temperatures that this species encounters in the natural environment. Previous results showed that the same treatment affects the brain proteome and the behaviour of adult zebrafish by producing alterations in the proteins involved in neurotransmitter release and synaptic function and impairing fish exploratory behaviour. In this study, we have investigated the performance of treated and control zebrafish during environmental exploration by using four behavioural tests (novel tank diving, light and dark preference, social preference and mirror biting) that are paradigms for assessing the state of anxiety, boldness, social preference and aggressive behaviour, respectively. The results showed that heat treatment reduces anxiety and increases the boldness of zebrafish, which spent more time in potentially dangerous areas of the tank such as the top and the uncovered bright area and at a distance from the social group, thus decreasing protection for the zebrafish. These data suggest that the increase in ambient temperature may compromise zebrafish survival rate in the natural environment.

Environmental temperature variation affects brain protein expression and cognitive abilities in adult zebrafish (Danio rerio): A proteomic and behavioural study.

Water temperature is an important environmental parameter influencing the distribution and the health of fishes and it plays a central role in ectothermic animals. The aim of this study is to determine the effects of environmental temperature on the brain proteome and the behavioural responses in zebrafish, a widely used animal model for environmental "omics" studies. Adult specimens of wild-type zebrafish were kept at 18 °C, 34 °C and 26 °C (control) for 21 days. Proteomic data revealed that several proteins involved in cytoskeletal organization, mitochondrial regulation and energy metabolism are differently regulated at the extreme temperatures. In particular, the expression of proteins associated to synapses and neurotransmitter release is down-regulated at 18 °C and 34 °C. In both thermal conditions, fish exhibited a reduced interest for the novel environment and an impairment of cognitive abilities during Y-Maze behavioural tests. The observed pathways of protein expression are possibly associated to functional alterations of the synaptic transmission that may result in cognitive functions impairment at central nervous system level as those revealed by behavioural tests. This study indicates that temperature variations can elicit biochemical changes that may affect fish health and behaviour. This combined approach provides insights into mechanisms supporting thermal acclimation and plasticity in fishes. SIGNIFICANCE: Environmental temperature variation may impact on all levels of biological life. Understanding the impact of thermal variation on the nervous system and animal behaviour is of primary importance since the results obtained can be applied from the ecological to the biomedical fields.

Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data.

BACKGROUND: Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infarction. Recent advances in pharmacological treatment of myocardial infarction may have changed the impact of this arrhythmia. OBJECTIVE: To assess the incidence and prognosis of atrial fibrillation complicating myocardial infarction in a large population of patients receiving optimal treatment, including angiotensin converting enzyme (ACE) inhibitors. METHODS: Data were derived from the GISSI-3 trial, which included 17 944 patients within the first 24 hours after acute myocardial infarction. Atrial fibrillation was recorded during the hospital stay, and follow up visits were planned at six weeks and six months. Survival of the patients at four years was assessed through census offices. RESULTS: The incidence of in-hospital atrial fibrillation or flutter was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure) and with some adverse clinical events (reinfarction, sustained ventricular tachycardia, ventricular fibrillation). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99). CONCLUSIONS: Atrial fibrillation is an indicator of worse prognosis after acute myocardial infarction, both in the short term and in the long term, even in an unselected population.

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.

OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Thromboembolism after atrioventricular node ablation and pacing: long term follow up.

OBJECTIVE: To assess the incidence of arterial embolic events in patients with high rate, drug resistant, severely symptomatic paroxysmal and chronic atrial fibrillation who have undergone atrioventricular (AV) node ablation and permanent pacing. DESIGN: Multicentre retrospective cohort study. PATIENTS AND MANAGEMENT: From May 1987 to January 1997, AV node ablation was performed in 585 severely symptomatic patients (mean (SD) age 66 (11) years) with high rate, drug resistant paroxysmal atrial fibrillation (308) or chronic atrial fibrillation (277). Lone atrial fibrillation was present in 133 patients, while the remaining 452 suffered from dilated, ischaemic, or valvar heart disease. Patients underwent VVIR (454) or DDDR (131) pacemaker implantation, after AV node ablation. Antiplatelet agents were given to 202 patients, warfarin to 187 patients. RESULTS: During a follow up of 33.6 (24.2) months, thromboembolic events were observed in 17 patients (3%); the actuarial occurrence rates of thromboembolism were 1.1%, 3%, 4.2%, and 7.4% after one, three, five, and seven years, respectively. Among five variables, univariate analysis showed that only the presence of chronic atrial fibrillation at the time of ablation (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.02 to 3. 20, p = 0.04) and the need for warfarin treatment (RR = 1.6, 95% CI 1.00 to 2.71, p = 0.048) were associated with a significantly higher risk of occurrence of thromboembolic events. On multivariate analysis the only predictor of embolic events during the follow up was the presence of chronic atrial fibrillation. CONCLUSIONS: Data from this large cohort of patients indicate a fairly low incidence (1.04% per year) of thromboembolic events after AV node ablation and pacing for drug refractory, high rate atrial fibrillation.

The effect of heart rate on the slope and pressure half-time of the Doppler regurgitant velocity curve in aortic insufficiency.

The effect of the heart rate on the Doppler aortic regurgitant velocity curve was evaluated in 14 patients with aortic regurgitation. The heart rate was increased in two steps with either endocardial or transesophageal pacing in 12 patients and with atropine sulfate in 2 patients (increased from 66 +/- 7 to 82 +/- 4 beats per minute [step 1] to 100 beats per minute [step 2]) in all patients. The increased heart rate resulted in an increased regurgitant slope (from 3.3 +/- 1.2 to 4.5 +/- 1.7 m/s2 [step 1] to 5.8 +/- 1.9 m/s2 [step 2]; p < 0.01) and a shortened pressure half-time (PHT) (from 442 +/- 136 to 323 +/- 98 ms [step 1] to 254 +/- 69 ms [step 2]; p < 0.01). Such variations occurred in the presence of a prevalent hemodynamic improvement, noninvasively suggested by a decreased Doppler-derived left ventricular end-diastolic pressure (LVEDP) (from 23 +/- 10 to 14 +/- 10 mmHg at the highest heart rate; p < 0.05) and by an increased peak aortoventricular diastolic gradient (from 80 +/- 20 to 84 +/- 22 at the highest heart rate; p < 0.05). The PHT and slope correlated with diastolic time (r = 0.74 and -0.65, respectively; p < 0.001). The relative-PHT (PHT/diastolic time x 100) showed insignificant changes during the increase in heart rate and correlated better than the PTH with color Doppler assessment of regurgitation severity (r = -0.73; p = 0.003, and r = -0.53; p = 0.05, respectively). We concluded that the slope and PHT of the aortic regurgitant velocity curve were rate-dependent; the relative-PHT appeared to limit the influence of the heart rate on PHT.

[Surgery of abdominal aortic aneurysms in octogenarians. Critical remarks on indications for surgical intervention in different age groups]. / La chirurgia degli aneurismi dell'aorta addominale negli ottuagenari. Riflessioni critiche sulla indicazione all'intervento chirurgico nelle varie fasce d'età.

Following the increased frequency of surgery for aortic abdominal aneurysm, due to increasing population age and to improved surgical and anaesthesiological techniques, results in octogenarians are presented and compared. The analysed data derive from 809 consecutive patients operated between January 1987 and December 1993. These have been divided into three age groups: group A = under 65 years, group B = from 65 to 79, group C = from 80 to 93. For each group surgery has been divided in planned operations (symptomatic and asymptomatic cases) and emergency operations (performed after aneurysm rupture) and results are compared. Surgery has been performed as an emergency in 8.6% of cases of group A, in 18.4% of group B and in 41.3% of cases of group C. Death rate in the three groups was respectively of 1.78%, 1.90% and 4.68% for planned operations and 12.50%, 32.63% and 46.67% for the emergency operations. These data confirm the experience of other Authors and indicate that age factor must not be considered a controindication for planned surgery. The importance of this factor in emergency surgery, the greater frequency of ruptures with increased age and the quality of the results in planned surgery suggest a widening of the indications for surgery: the aneurysm transverse diameter of 5 cm, as a minimal measure for planned surgery, must be reconsidered.

[The noninvasive quantitative evaluation of the acute hemodynamic effects of sublingual and transdermal nitroglycerin in man]. / Valutazione quantitativa non invasiva degli effetti emodinamici acuti della nitroglicerina sublinguale e transdermica nell'uomo.

BACKGROUND: Organic nitrates are complex vasodilators: the hemodynamic action of these drugs is different in the venous and arterial resistance and capacitance beds. The aim of our study was to obtain a quantitative, noninvasive evaluation of the acute effects of sublingual and transdermal (td) nitroglycerin (NTG). METHODS: Twenty-one pts (mean age 49 years) underwent strain-gauge plethysmography and digital photoplethysmography under control conditions, 5 min after sublingual NTG (0.4 mg), 1 hour thereafter and 2 hours after NTG td (10 mg patch). Forearm venous capacitance (CV, ml.100 ml-1) and arteriolar resistance (RA, mmHg.ml-1.100 ml.min) and the b/a ratio of arterial pulse wave (%) were measured. RESULTS: After sublingual NTG, CV increased (+24%, p < 0.01) and b/a was reduced (-35%, p < 0.01), while heart rate and RA increased (+9% and +36% respectively, both p < 0.01). Two hours after NTG td, CV increase was not statistically significant (+11%, p = 0.056), b/a was reduced (-31%, p < 0.01), heart rate and RA did not change. CONCLUSIONS: The combined use of plethysmography and digital photoplethysmography is suitable for the evaluation of vasoactive drugs such as nitrates, which have a complex profile of action on arterial and venous beds. By this method we have shown that NTG td 10 mg dilates venous beds to a low extent; this approach will be utilized in future studies aimed at elucidating dose-response and regimen effect of these drugs.

[Study of the retroperitoneal lymphatic spread of müllerian ovarian carcinoma, using lymphography]. / Studio sulla diffusione linfatica retroperitoneale del carcinoma ovarico mülleriano mediante l'impiego della linfografia

From January 1973 to May 1974, 117 patients with ovarian carcinomas were evaluated with lymphography. The tumors were staged and classified histopathologically according to FIGO (1971). Considering all cases, lymphography showed nodal metastases in 44 patients (38%). Lymphography was positive in 36% of serous cystoadenocarcinomas, in 26% of mucinous cystoadenocarcinomas, in 15% of endometrioid carcinomas and in 36% of unclassified carcinomas. Of the 10 cases not identified by cell type, lymphography was positive in 40% of cases. In 68% of cases bilateral involvement was found. The site of metastatic nodes was in 32% of cases only in the iliac chains were both involved. Considering the single node chains we found 36% of para-aortic, 27% of common iliac, 35% of external iliac and 2% of inguinal involvement. Metastases were observed, regardless of histological type, in 25% of cases in stage III, 62% iin stage IV, 54% in recurrences and only in 5% of cases in stage I. Therefore the lymphatic spread seems to occur in more advanced stages and in recurrences. In 28 of 117 patients node biopsy was performed. Histological-lymphographic correlation was correct in 7/7 positive cases and in 19/21 negative cases (93%). These results show that lymphography is a reliable tool in the evaluation of ovarian cancer.

Staging laparotomy in non-Hodgkin's lymphomata.

Staging laparotomy was performed in 106 selected untreated adults and in 6 children. In adults the histological pattern at initial biopsy was interpreted as nodular lymphoma in 33% and as diffuse lymphoma in 67%. Diffuse histiocytic was the most frequently observed histological subtype in the present series (54%). Diffuse undifferentiated lymphoma was noted in 2/6 children. Waldeyer's ring involvement was noted in 27% of adult patients. Systemic symptoms were present in 7%. Surgery detected occult lesions in 27% of patients (para-aortic nodes 3%, spleen 12%, liver 12%, coeliac nodes 15%, splenic hilar nodes 26%, mesenteric nodes 15%, gastrointestinal tract 1%, bone marrow 12%). The chance of detecting splenic and hepatic involvement was definitely higher in patients with nodal disease above and below the diaphragm in comparison with those with either supra-diaphragmatic or infra-diaphragmatic adenopathy. Lymphography yielded a 96% accuracy proving once more to be a sufficiently reliable diagnostic method. Staging laparotomy is a useful procedure in non-Hodgkin's lymphomata in order to gain information on the natural history and to plan treatment. It remains to be determined whether findings observed through surgical staging will lead to improved treatment and survival.