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Biomedical subjects

R Bussani

Publications and source records attributed to R Bussani.

At least 19 recordsLinked to original sources

Cardiac metastases.

Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others--for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions.

Heart Neoplasms↗

Giant omphaloceles with a small abdominal defect: prenatal diagnosis and neonatal management.

A giant omphalocele is a liver-containing protrusion through an abdominal defect wider than 5 cm in diameter. The giant form with a small abdominal wall defect is a rare condition which, to our knowledge, has not been described previously. We describe three cases with the typical features of elongated vascular liver pedicle and angiomatosis of the hepatic portal system. The abnormal liver organogenesis, due to extra-abdominal development, represented a significant risk factor for hepatic thrombosis after visceral reduction and liver rotation. All the neonates underwent surgery on the first day of postnatal life. One died because of a postoperative liver infarction, and the survivors needed prolonged respiratory support. Prenatal sonographic features, timing, delivery, type of surgical repair, and postnatal outcome are reviewed. A prenatal sonographic diagnosis could be useful to evaluate the abdominal ring and serial ultrasound examinations are recommended to detect promptly ominous signs of hepatic and bowel damage. Color Doppler may be useful to assess the anatomy of the abdominal vessels and their relationships with the herniated organs, although it was not used in any of the cases reported here. This congenital malformation might be considered as a pathological entity separate from giant omphalocele with large abdominal defect, with a severe prognosis due possibly to its different embryological development.

Abdominal Wall↗

Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?

BACKGROUND: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. OBJECTIVE: To assess COX-2 expression at the site of recent myocardial infarction. METHODS: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. RESULTS: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). CONCLUSIONS: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

Aged↗

Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction.

BACKGROUND: Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown. AIM: To evaluate survivin expression after acute myocardial infarction (AMI). METHODS: Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in four control hearts. RESULTS: Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infarct regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. CONCLUSIONS: Survivin myocardial expression after AMI may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling.

Apoptosis↗

High-risk clinical features predict increased post-infarction myocardial apoptosis and the benefits as a result of an open infarct-related artery.

BACKGROUND: Infarct-related artery (IRA) patency after acute myocardial infarction (AMI) is associated with a more favourable clinical course, in particular in patients with high-risk features. As it has been recently reported that IRA patency is associated with a reduced postinfarction apoptotic rate (AR), the aim of our study was to assess whether IRA status late after AMI had a different impact on AR in high- vs. low-risk patients. METHODS AND RESULTS: Co-localization of TUNEL and caspase-3 was used to calculate the AR at the site of infarction at the time of death in 30 subjects. The Norris coronary prognostic index (NI) was calculated (computing age, presence of pulmonary congestion, heart size and history of previous additional AMI) in order to define the patients' individual risk at the time of hospitalization. According to the NI (< or =7 vs. >7), subjects were divided into low and high risk, as NI >7 carries an approximate threefold higher risk of death. The NI was significantly correlated with the AR at the time of death both in infarct and remote areas. Twenty subjects had IRA occlusion at the time of death, and in these patients AR was significantly higher both in infarct and remote areas (P<0.001 and P=0.009 vs. the others, respectively). However the impact of IRA occlusion on AR was significantly different comparing high- vs. low-risk subjects. In particular, AR at the infarct site was 10-fold higher in the high-risk subjects with IRA occlusion (26.1%[20.4-28.7%]) vs. those with open IRA (2.3%[0.6-3.5%]; P=0.002) and was nonsignificantly different in the low-risk subjects vs. those without IRA occlusion (8.2%[2.5-17.5%] vs. 5.4%[1.5-7.9%]; P=0.48). Similarly, in the high-risk subjects, AR in remote areas was significantly greater in cases with occluded vs. open IRA (0.7%[0.4-0.9%] vs. 0.3%[0.3-0.32%]; P=0.009). CONCLUSION: A significantly higher AR is associated with IRA occlusion late post AMI in subjects with high-risk clinical features, and not in low-risk patients. The diverse impact of IRA occlusion on AR in subjects with different risk profiles may explain the greater benefit associated with coronary reperfusion in high-risk subjects. The overall lower AR in low-risk subjects, independently from the IRA status, may be correlated with the better long-term prognosis after AMI in this case.

Aged↗

Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans.

BACKGROUND: Cardiac remodelling after acute myocardial infarction (AMI) is characterised by molecular and cellular mechanisms involving both left and right ventricles, and biventricular failure identifies patients with an extremely unfavourable prognosis. AIMS: To assess whether a link exists between increased myocardial apoptotic rates (AR) at sites of recent infarction and patterns of unfavourable cardiac remodelling, such as biventricular enlargement after left ventricular (LV) infarction. METHODS: Twelve patients with recent AMI involving the LV and not the right ventricle (RV) and with permanent infarct related artery occlusion were selected at necropsy. Gross pathological characteristics, such as LV and RV dilatation, and AR at site of infarction were assessed. Potential false positive results (DNA synthesis and RNA splicing) were excluded from the cell count. RESULTS: RV enlargement, defined as a tricuspidal ring greater than 120 mm, was found in five cases and was associated with LV dilatation. These patients showed significantly higher AR than the others. When the subjects were divided into three groups according to progressive cardiac remodelling (absence of cardiac dilatation, isolated LV dilatation, and biventricular enlargement), the last group had significantly higher ARs than the other two groups, showing that myocardiocyte apoptosis is increased in more unfavourable forms of cardiac remodelling. CONCLUSION: Patients with severely unfavourable cardiac remodelling, such as biventricular enlargement, have extremely high myocardiocyte apoptosis at necropsy, even late after LV myocardial infarction, supporting the role of myocardiocyte loss in determining post-infarction adverse remodelling.

Aged↗

Cytomegalovirus endocarditis. A case report and a review of the literature.

The authors describe the case of a 75-year-old man admitted to our intensive care unit due to coma and respiratory failure; the history revealed a chronic renal failure due to an ANCA+ arteritis; subsequently, he developed a thrombotic thrombocytopenic purpura which was treated with plasma exchange. During his clinical course the patient developed polymicrobial and fungine sepsis and ultimately died. The autopsy demonstrated a severe cytomegalovirus endocarditis, which is extremely uncommon in non-immunodepressed patients as those receiving a solid-organ transplantation.

Aged↗

Intractable fever and cortical neuronal glycogen storage in glycogenosis type 2.

Glycogenosis type 2 is an autosomal recessive glycogen storage disorder caused by deficiency of lysosomal acid alpha-glucosidase. Different phenotypes are recognized. The authors describe two children affected by the late infantile form; both presented terminal hyperthermia not caused by infections. Autopsy performed in one case showed diffuse glycogen storage in the CNS neurons. In light of current interest in enzyme replacement therapy, this finding casts some doubt on how effective enzyme replacement therapy will be unless it can be targeted directly into the CNS.

Cerebral Cortex↗

Evidence that human cardiac myocytes divide after myocardial infarction.

BACKGROUND: The scarring of the heart that results from myocardial infarction has been interpreted as evidence that the heart is composed of myocytes that are unable to divide. However, recent observations have provided evidence of proliferation of myocytes in the adult heart. Therefore, we studied the extent of mitosis among myocytes after myocardial infarction in humans. METHODS: Samples from the border of the infarct and from areas of the myocardium distant from the infarct were obtained from 13 patients who had died 4 to 12 days after infarction. Ten normal hearts were used as controls. Myocytes that had entered the cell cycle in preparation for cell division were measured by labeling of the nuclear antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined, and the mitotic index (the ratio of the number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. The presence of mitotic spindles, contractile rings, karyokinesis, and cytokinesis was also recorded. RESULTS: In the infarcted hearts, Ki-67 expression was detected in 4 percent of myocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts. The reentry of myocytes into the cell cycle resulted in mitotic indexes of 0.08 percent and 0.03 percent, respectively, in the zones adjacent to and distant from the infarcts. Events characteristic of cell division--the formation of the mitotic spindles, the formation of contractile rings, karyokinesis, and cytokinesis--were identified; these features demonstrated that there was myocyte proliferation after myocardial infarction. CONCLUSIONS: Our results challenge the dogma that the adult heart is a postmitotic organ and indicate that the regeneration of myocytes may be a critical component of the increase in muscle mass of the myocardium.

Antibodies, Monoclonal↗

Absence of connections between spinal nerves and the spinal cord in a twin fetus: a very rare malformation occasionally evidenced at autopsy.

We describe a rare case of spinal cord malformation in a dichorionic diamniotic twin fetus aborted at 20 weeks' gestation due to acute chorioamnionitis with placental dysmaturity probably caused by a maternal viral infection. At autopsy, there were no connections between the spinal nerves and the spinal cord. The spinal cord lacked the posterior median fissure and gray matter; only a few neurons were present in the anterior and lateral gray columns. No chromosome anomalies were found. Although we cannot reconstruct the pathogenetic chain of events leading to this malformation, we believe that it is correlated with a maternal viral infection. We hypothesize that this viral infection altered the delicate balance between the factors inducing and those inhibiting fetal spinal neural differentiation.

Abortion, Spontaneous↗

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust.

To understand the dermal uptake of chemicals bound to soil and dust, information on the neat substance is helpful but does not seem sufficient. Because of its content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be carcinogenic. However, experimental carcinogenity studies on coal dust never succeeded in demonstrating a higher incidence of cancer in treated animals. The aim of the study was to assess dermal penetration through human skin of PAHs from coal dust. A sample of coal dust was grinded and sieved, using the particle size of < 30 microm. An in vitro static diffusion cell system validated by in vitrolin vivo comparison has been used to study dermal penetration through human skin of PAHs from coal dust compared with their percutaneous absorption as pure compounds. No percutaneous penetration of PAHs was observed in the cells where coal dust was applied, while dermal penetration was demonstrated for PAHs applied in an acetone solution. Results agree with the literature that PAHs are poorly absorbed through the skin from solids. Dermal risk assessment of PAHs should take into account not only the degree and the extent of skin contamination, but also their bioavailability, which is heavily influenced by the physico-chemical characteristics of the matrix.

Administration, Cutaneous↗

An uncommon cause of lower limb weakness.

We describe a case of a severely mentally disabled patient diagnosed as suffering from Guillain-Barré syndrome and treated with repeated plasma exchange. However, the abrupt onset of a cardiovascular collapse prompted a more in-depth diagnostic workup which demonstrated that the neurologic symptoms were likely to be ascribed to poisoning with heavy metals from a large number of ingested coins and other metallic items.

Aluminum↗

Early screening for fetal cardiac anomalies by transvaginal echocardiography in an unselected population: the role of operator experience.

OBJECTIVES: To examine the accuracy of early transvaginal fetal echocardiography performed in an unselected population by operators with different levels of experience and to compare the results with those obtained from a referral population. DESIGN: Prospective study. METHODS: A series of 4785 unselected fetuses and 221 referred fetuses were screened at 13-15 weeks' gestational age by transvaginal echocardiography. For each fetus, visualization of the four-chamber view plus the origin of the great arteries was attempted. Color Doppler imaging was only performed in cases of cardiac malformations already identified by two-dimensional echocardiography. The scans were performed by seven operators with different levels of experience. Reliability was assessed by conventional transabdominal echocardiography at 20-22 weeks, by postnatal follow-up in the first 3 months of life, and/or by autopsy in all cases of termination or fetal death. RESULTS: The rate of complete visualization (four-chamber view plus great arteries) was 47.5% in the unselected population, and 76.9% in the referral population. There were four (0.08%) true positives among the unselected fetuses, and five (2.3%) among referrals, mostly with enlarged nuchal translucency or other malformations. Among the unselected fetuses, nine false negatives were detected by transabdominal echocardiography. Improvement in the operators' ability to recognize cardiac anomalies in unselected population was disappointing and was influenced more by individual approach than by the number of examinations performed. CONCLUSIONS: Early screening for cardiac anomalies among unselected fetuses is ill-advisable. The usefulness of an early approach is confirmed in high risk fetuses or in the presence of enlarged nuchal translucency when performed by expert operators.

Adult↗