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Biomedical subjects

G Bartoloni

Publications and source records attributed to G Bartoloni.

At least 19 recordsLinked to original sources

New model of liver regeneration induced through use of vascular endothelial growth factor.

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen. The objective of this study was to verify the proregenerative effects of VEGF in an experimental model of acute liver failure. MATERIALS AND METHODS: Sixty four rats that underwent intraperitoneal injection of carbon tetrachloride (CCl(4)) were randomly divided into two groups: group B animals received intravenous injection of VEGF(164) 1 hour following CCl(4) poisoning. Group A hosts were untreated. To obtain daily liver function tests (LFTs) and histological samples, on each day up to 8 days we sacrificed four rats in each group. RESULTS: The laboratory examinations showed notable alteration of LFTs in group A, while group B revealed only slight changes. The histological examination showed greater liver damage in group A compared with group B. CONCLUSION: Our results suggest that administration of exogenous VEGF protects the liver from CCl(4)-induced acute hepatic failure. Further studies are underway to assess whether exogenous VEGF is effective in other liver injuries.

Alanine Transaminase↗

Prenatal 2-dimensional and 3-dimensional ultrasonography diagnosis and autoptic findings of isolated ectopia cordis.

Ectopia cordis is a very rare congenital malformation, commonly associated with intracardiac anomalies. It is due to a defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. We report prenatal 2-dimensional (2D) and 3D ultrasonography diagnosis and postnatal autoptic findings of an isolated ectopia cordis with tricuspid atresia. Ectopia cordis prenatal diagnosis is easily made with ultrasound by visualizing the heart outside the thoracic cavity. 3D ultrasonography may add more detailed visualization of the heart anomaly even if the 2D ultrasonography alone permits the prenatal diagnosis. Obstetrical management should include a careful search for associated anomalies, especially cardiac, and the assessment of fetal karyotype. As this is considered a sporadic anomaly, the recurrence risk is low and no genetic origin is known.

Adult↗

Prenatal and postnatal findings of acrania.

INTRODUCTION: Acrania is a rare congenital anomaly in which the flat bones of the cranial vault are partial or complete absent with complete but abnormal development of the cerebral hemispheres. CASE REPORT: We report two cases, diagnosed prenatally by ultrasound and followed by medical pregnancy termination, one with isolated acrania and one with associated cleft lip and palate and spina bifida. DISCUSSION: The acrania pathogenesis is unknown and differential diagnosis should be made with other conditions like anencephaly and acalvaria. Genetic counselling is not easy because there is no evidence for a specific genetic origin, but the extreme rarity and sporadic nature suggests a low recurrence risk.

Abortion, Induced↗

[Innovative use of the vascular endothelial growth factor in an experimental model of acute liver failure].

Vascular Endothelial Growth Factor (VEGF) is an endothelial cell mitogen and an important stimulator of sinusoidal endothelial cell proliferation. The aim of this research was to study the effects of exogenous VEGF in a rat model of acute liver failure. The study was conducted on 64 rats (240-300 g). All rats underwent intraperitoneal injection (5 ml/kg) of 25% carbon tetrachloride (CCl4) and 75% paraffin oil. This dosage of CCl4 was devised to induce nonfatal acute liver failure with spontaneous recovery in 7 days. The animals were randomly divided into 2 groups. Group B animals underwent i.v. injection of 200 ng of VEGF165 one hour following intra-peritoneal injection of CCl4. To obtain daily liver functional tests (LFTS) and histological liver samples, 4 rats in each group were sacrificed daily up to 8 days. In group A, the liver histology showed massive periportal hepatocyte necrosis associated with portal lymphocytic infiltrates. The peak of the damage was documented at 72 hours following CCl4. Group B showed minimal necrosis, moderate periportal edema and a minimum periportal steatosis. At 48 hours steatotic changes had disappeared and the periportal edema was resolving. LFTs demonstrated severe liver damage in rats in group A. In group A the peak AST (mean 322.5 IU/L) and ALT (mean 250.25 IU/L) were recorded at 72 hours. In group B, at 72 hours the mean AST was 137 IU/L (normal < 95 IU/L) and ALT 68 IU/L(normal < 45 IU/L). The maximum levels of AST and ALT, in group B, were 152.3 IU/L and 72.3 IU/L, at 24 hours. According to our results exogenous VEGF successfully protects the liver from CCl4 induced acute liver failure. Further studies will demonstrate if exogenous VEGF can be effective in other liver injuries.

Animals↗

Accelerated cardiomyopathy in maternally inherited diabetes and deafness.

The clinical features and course of cardiac involvement in a patient with maternally inherited diabetes and deafness associated with the mitochondrial DNA 3243 mutation are reported. A 45-year-old woman with maternally transmitted diabetes mellitus and deafness presented with congestive heart failure. The patient showed a short P-R interval on electrocardiogram (ECG) and had developed progression from left ventricular hypertrophy to a hypokinetic cardiomyopathy pattern over the course of 10 months. Rapid cardiac change was accompanied by left ventricular remodeling, as shown by wall thinning on echocardiogram and decrease in QRS voltages on ECG. Coronary arteriography revealed no significant stenosis. In the endomyocardial biopsy specimens, light microscopy showed nonspecific cardiomyopathic changes. Genetic testing for mitochondrial DNA mutations in peripheral blood lymphocytes revealed an adenine (A)-to-guanine (G) substitution at nucleotide 3243 in the mitochondrial DNA encoding the transfer RNA for leucine (tRNA Leu (UUR)). The proportion of mutant mitochondrial DNA was 25%. Two of the patient's daughters, aged 13 and 21 years, who were symptom free, were found to carry the same point mutation. A short P-R interval on ECG in the younger of them was the sole manifestation of the mutation. Unfortunately, 6 months after diagnosis, the patient died suddenly at home. Accelerated cardiomyopathy can occur as a mitochondria-related complication in patients with maternally inherited diabetes and deafness associated with the 3243 mutation.

Adolescent↗

Neonatal diaphragmatic hemangioma.

The first neonatal case of a hemangioma of the diaphragm in a neonate is reported. After 25 months the patient is well with no signs of recurrence. Diaphragmatic tumors should be considered in the differential diagnosis of neonatal thoracic masses.

Diaphragm↗

Expression of alpha6 and beta4 integrin subunits on human endometrium throughout the menstrual cycle and during early pregnancy.

OBJECTIVE: To evaluate the expression of alpha6 and beta4 integrin subunits on surface and glandular endometrium throughout the menstrual cycle and during early pregnancy. SETTING: Second Department of Obstetrics and Gynecology, University of Catania, Catania, Italy. PATIENT(S): Thirty-two women. Nineteen of the women regularly menstruated in different phases of the cycle, and 13 were in the sixth to ninth week of gestation and required voluntary abortion. INTERVENTION(S): Endometrial specimens collected during endometrial biopsy, hysterectomy, or voluntary abortion. MAIN OUTCOME MEASURE(S): Immunohistochemical staining for alpha6 and beta4 integrin subunits in endometrial tissues. RESULT(S): Both subunits (poorly expressed in preimplantation days) reached a significant peak on the endometrial surface during the implantation window, which tended to disappear in the postimplantation phase. On glandular endometrium they exhibited an opposite trend, showing high levels in the preimplantation and postimplantation days, whereas their expression decreased during the implantation window. The two subunits tended to disappear in early pregnancy. CONCLUSION(S): alpha6 and beta4 integrin subunits are uniformly distributed and highly expressed on the endometrial surface during the implantation window; they decreased dramatically in the postimplantation phase. These results could suggest involvement of integrin-extracellular matrix components in blastocyst-endometrium interaction during the early stages of implantation.

Adult↗

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.

Bacterial Infections↗

Cardiac iron overload in thalassemic patients: an endomyocardial biopsy study.

Secondary heart failure induced by organ siderosis is the main cause of death in patients affected by thalassemia major. At present it cannot be predicted whether heart siderosis is correlated with iron overload and little is known about the real cardiac histological pattern of post transfusional hemochromatosis in patients with thalassemia major and intermedia. The study aim was to evaluate cardiac iron overload by non invasive and invasive techniques. Fifteen thalassemic patients were investigated and endomyocardial biopsy performed in ten revealed different grades of endomyocardial iron overload with histochemical positivity. Non invasive techniques are not able to furnish an exact picture of the cardiac hemochromatosis. There was a significant correlation between serum ferritin and myocardial iron grade. Patients with elevated ferritin levels and poor compliance to chelating therapy are at high risk of severe heart hemochromatosis. It was seen that endomyocardial biopsy is a useful tool in studying myocardial iron.

Adult↗

Leiomyomatosis with vascular invasion. A unified pathogenesis regarding leiomyoma with vascular microinvasion, benign metastasizing leiomyoma and intravenous leiomyomatosis.

Three uterine leiomyomas with vascular invasion (LWVI), two of which were associated with pulmonary leiomyomatous nodules, and a case of intravenous leiomyomatosis (IVL) invading the vena cava and extending to the right atrium, are described. Despite their histological benignity, these lesions have a strong tendency to metastasize and are closely related to the so-called benign metastasizing leiomyoma (BML). From a clinical point of view, the pulmonary nodules of LWVI are stable or slowly-growing. The IVL was a "worm-like" tumour that presented as a cardiac mass. On the basis of their histological and immunohistological features, a unified histogenetic view of LWVI, IVL and BML of the uterus is proposed. LWVI and BML may be the same pathological entity and microscopic vascular invasion may represent the metastatic mechanism of BML. Alternatively, LWVI may be the initial stage of IVL. In rare instances, IVL may be associated with distant parenchymal (pulmonary) metastases. LWVI seems to be the precursor of both BML and IVL.

Adult↗

[Echocardiography in the early diagnosis of acute rejection in patients with heart transplant].

The aim of our study was to assess the sensibility and specificity of Doppler echocardiographic evaluation of left ventricular diastolic function during acute cardiac rejection. We studied 34 patients who had undergone a recent heart transplant and compared the echocardiographic results with the histologic findings. We considered the following parameters of left ventricular filling: early peak of mitral flow velocity; pressure half-time (PHT); isovolumic relaxation time (IVRT). We divided the patients into two groups according to the histologic findings: Group I (25 patients who had at least 1 episode of mild-moderate rejection), Group II (6 patients without documented rejection after at least three consecutive biopsies). Three patients with clinically evident rejection were excluded from the analysis. In Group I cardiac rejection was associated with a statistically significant decrease in IVRT (p < 0.0005), without significant changes in heart rate and in the early peak of mitral flow velocity. In Group II Doppler parameters remained unchanged. These variations were not associated with changes in echocardiographic morphologic parameters and in parameters of ventricular systolic function. IVRT and PHT returned to normal values after adequate immunosuppressive treatment. Considering variations of IVRT and PHT of at least 20%, we obtained a sensibility of 88% for isolated variations of PHT and a specificity of 93% for consensual variations of PHT and IVRT. Therefore, the assessment of the left ventricular diastolic function by Doppler echocardiography represents a safe and non-invasive method for an early detection of acute cardiac rejection.

Acute Disease↗

When and why do heart transplant recipients die? A 7 year experience of 1068 cardiac transplants.

This mortality study deals with the 1068 heart transplants (1054 patients) performed in Italian Units from November 1985 to April 1992. The death rate was 19.7% and the actuarial survival was 89% at 1 month, 83% at 1 year and 74% at 6.5 years. Recipients who died had been less often transplanted for dilated cardiomyopathy, were older (44.1 vs. 41.7 years) and more often male (84.5 vs. 72.7%). Analysis of the causes of death was restricted to orthotopic transplantations (1029/1068 procedures, 195/208 deaths). Deaths were grouped within four intervals: peri-operative (< or = 1 month, 50.0% of deaths), early (> 1 month < or = 3 months, 17.2%), intermediate (> 3 months < or = 2 years, 22.6%) and late (> 2 years, 10.2%). The prime causes of death were mostly postoperative graft failure (whose effects brought about 64% of peri-operative deaths, 28% of early and 7% of intermediate deaths), post-operative complications (10% of peri-operative deaths), acute rejection (10% of total deaths, distributed in all the periods), graft arteriopathy (6% of early, 36% of intermediate and 58% of late deaths), infections (17% of deaths, occurring in all periods but late) and malignant tumours (7% of deaths), lymphomas being the first to occur and Kaposi's sarcoma occurring only in the intermediate period. Repeat transplantation had a poor outcome (death rate 71.4%), two-thirds of the re-transplanted patients' deaths being due to early graft failure and a third to late relapsing graft vasculopathy.

Adult↗

[The contribution of pathology sections to the Italian Heart Transplant Project in the first 5 years of its activities (1985-1990)].

All the transplantation units within the Italian Heart Transplantation Project are supported by a section of pathology, devoted to the study of the recipient's heart, to patient monitoring by means of a schedule of endomyocardial biopsies, and, if that was the case, to examine the donor's heart and to analyse the causes of death. When successes and failures of the first five years of the Project's activity are weighed up, good results are observed: of the 847 operations performed (orthotopic, heterotopic and heart-lung transplants, and re-transplants) an actuarial survival rate of 77% at 5 years has been achieved. The sections of pathology believe to have contributed significantly to these results, examining as many as 10,446 endomyocardial biopsies. The indications for transplantation were: dilated cardiomyopathy (48.5%); ischemic (35.3%); valvular (5.9%) and congenital (2.4%) heart disease; hypertrophic cardiomyopathy (2.2%); endocardial fibroelastosis (1.7%); restrictive cardiomyopathy (1.4%); anthracycline cardiotoxicity (0.8%); myocarditis (0.8%); cardiac tumours (0.5%) and arrhythmogenic cardiomyopathy (0.2%). Distribution of recipients by sex and age varied according to the indications for transplantation: males were more common among the patients transplanted for ischemic (97%) and valvular (84%) heart disease, as well as for dilated (82%) and hypertrophic (78%) cardiomyopathy, whereas the opposite was true for endocardial fibroelastosis (males constituting 21%) and cardiac tumours (25%). Mean age at transplantation ranged from 49 years (ischemic heart disease) to 6 years (endocardial fibroelastosis). In the follow-up period, a 17.5% death rate was recorded; the main causes of death were the early failure of the transplanted heart (27 pts), postoperative complications (16), hyperacute rejection (4), acute rejection (18), infections (the singular most frequent cause of death, 35 pts), the proliferative endoarteritis of coronary branches (the so-called chronic rejection, that caused 21 deaths and required 14 re-transplants) and the development of neoplasms (11). The actuarial survival curve drops to 89% after the first postoperative month, abates to 82% at the end of the first year, and progressively decreases to 77% at the end of the fifth follow-up year. Rejection monitoring required an average number of 12.5 endomyocardial biopsies per recipient, and allowed 1.7 rejection episodes per patient to be diagnosed. The fewer were the rejection episodes occurring in a unit, the higher was the percentage of deaths due to infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Blockade of central and peripheral luteinizing hormone-releasing hormone (LHRH) receptors in neonatal rats with a potent LHRH-antagonist inhibits the morphofunctional development of the thymus and maturation of the cell-mediated and humoral immune responses.

The development of the thymus and the hypothalamic-pituitary-gonadal axis are linked by bidirectional hormonally mediated relationships. In the present study, the direct involvement of the neuropeptide LHRH in the maturation of the thymus and development of the cell-mediated and humoral immune responses were assessed after treatment of neonatal (from post-natal day 1-day 5) female rats with a potent LHRH-antagonist (LHRH-anta, p-Glu-D-Phe 2.6,Pro3-LHRH, 50 micrograms/rat), and the effects compared to those resulting from neonatal castration. Whereas in control animals the maturation of mitogenic potential in thymocyte cultures showed a progressive and age-dependent increase, reaching a maximal activity at 30 days of age and then decreasing after puberty onset, in LHRH-anta-treated rats, the thymocyte's proliferative response was completely blocked at 7 days of age and remained very low at each time interval studied, until 3 months of age. A similar effect of the LHRH-anta treatment on splenocyte cultures was measured. Moreover, a reduced percentage of the T-helper lymphocyte subpopulation followed LHRH-anta administration. By contrast, in neonatally castrated rats, blastogenic activity was significantly higher, compared to control cultures, at each stage studied. Treatment with LHRH-anta produced a significant decrease in thymus wt, an alteration of the maturational pattern characterized by a cellular monomorphism, reduced thymocyte volume, reduction of the cortical area, and depauperation of the epithelial microenvironment. Moreover, a morphometric analysis revealed a selective decrease in the large lymphoid cell population of the subcapsular cortex at 7 and 15 days. On the other hand, neonatal castration produced an opposite effect, leading to a marked hypertrophy of the cortical area, and counteracted the post-puberal thymus atrophy. When LHRH-anta-treated adult (3-month-old) rats were challenged with an antigenic stimulus (multiple sc injections of complete Freund adjuvant and BSA) and antibody (anti-BSA antibodies of the immunoglobulin G class) production measured in the serum after 15 days, a marked and significant decrease in immunoglobulin G levels was observed, compared to the values measured in untreated control. The described immune deficiencies in LHRH-anta-treated rats were associated with a clear inhibition of sexual maturation. This study clearly indicates that the blockade of central and peripheral LHRH receptors during a critical period for maturation of both hypothalamus-hypophyseal-gonadal axis and brain-thymus-lymphoid axis dramatically impairs immune system development, suggesting a potential role of the neuropeptide LHRH in the bidirectional programming of both neuroendocrine and immune functions.

Animals↗

Luteinizing hormone-releasing hormone-binding sites in the rat thymus: characteristics and biological function.

The present study was designed to explore the effects of LHRH and its agonists on immune system function. As a first step, to identify a putative site of action, the very potent and stable LHRH agonist (LHRH-A), [D-Ser(TBU6)] des-Gly10-LHRH ethylamide (buserelin), was used as an iodinated ligand to characterize LHRH receptors in a membrane preparation of rat thymus, a key organ of the immune system. The effects of LHRH and LHRH-A were then investigated on the proliferative capacity of rat thymocytes exposed in vitro to a mitogen and on ornithine decarboxylase specific activity. In addition, to determine whether LHRH-A treatment in vivo might directly influence thymic function, we treated hypophysectomized (hypox) rats with a moderately high dose of LHRH-A for a period of 2 weeks, and thymocyte mitogenic capacity, thymus weight, and the histological and functional appearance of the thymus were then assessed. Specific binding of LHRH-A to rat thymic membrane preparations is a saturable process, depending on both time and temperature of incubation, but differs markedly from binding to the rat pituitary or ovarian LHRH receptor in its low binding affinity. Binding is optimal in the absence of chelating agents (EDTA) or divalent metal ions, and increases linearly with increasing protein concentration. Binding is specific for LHRH, LHRH-A, and antagonists. Both the C-terminal amide and N-terminal regions of the LHRH molecule were required for binding, and amino acid substitutions at position 6 markedly enhanced and at position 8 markedly reduced binding potencies in rat thymic tissue. A number of peptides, proteins, and other agents had no effect on the specific binding of LHRH-A to thymic membrane preparations. The binding affinity (Ka) of the membrane receptor of the rat thymus for the LHRH superagonist buserelin was 8.4 x 10(8) M-1, while a higher binding affinity (Ka = 2.8 x 10(9) M-1) was calculated for the ovarian LHRH-binding site. Preincubation of rat thymocytes with LHRH-A for 20 h induced a significant dose-dependent increase in the proliferative response to the mitogen Concanavalin-A, monitored by [3H]thymidine incorporation. Using native LHRH, it was also possible to elicit stimulatory effects on the same parameter, although much higher concentrations were required than with LHRH-A. Furthermore, simultaneous addition of a LHRH antagonist, abolished the LHRH effect on thymocytes. Ornithine decarboxylase specific activity under lectin stimulation was also significantly increased by LHRH-A in cultures of rat thymocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗