Prevalence of depressive mood disorders in breast cancer patients of southern Italy.
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Biomedical subjects
Publications and source records attributed to M Aragona.
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1. In genetically epilepsy-prone rats (GEPR-9s), which represent a natural genetic model of epilepsy, we observed that the number of peritoneal macrophages was significantly lower with respect to normal rats, and that some functional parameters (i.e. phagocytosis and intracellular killing) of these macrophages were impaired. 2. The count of lymphocyte populations showed a predominance of T-helper over T-cytotoxic/suppressor both in the spleen and lymph nodes. Moreover, an increased T-cell/B-cell ratio was observed in GEPR-9s. Flow cytometry revealed that GEPR-9s spleens possessed a large percentage of T-helper cells in comparison to normal rats. 3. By using concanavalin A-induced proliferation of GEPR-9s cultured lymphocytes, we have shown increased functional activation. 4. We suggest that the alterations in T-cell functions in GEPR-9s could be due to the involvement of the neuroendocrine system in the modulation of immunity, in the shift between Th1 and Th2, and in the activation of stress response.
Estrogens are known to have mitogenic activities and to influence hematic crasis. A wide literature on this subject allows us to re-evaluate the results of research performed in 1950. Estrogens injected into the peritoneum (estradiol propionate 2.5-5 mg, twice weekly) or into tibial bone marrow (estradiol propionate 1.5 mg weekly) of guinea pigs, after carbon tetrachloride induced cirrhosis (CCI4 inhalation for 7-15 min twice weekly), caused hyperchromic anemia, with erythroblastosis and leucocytosis; hyperplasia of reticulo-hystiocitary cells of bone marrow and lymphoid organs; splenic hemosiderosis; hyperplasia of immature bone marrow cells, with maturative inhibition; and terminal bone marrow hypoplasia. Our results agree with recent literature data concerning the role played by natural estrogens and environmental xenoestrogens that are capable of stimulating bone marrow progenitor cell proliferation and delaying their maturation, by the secretion of growth factors, especially from hyperplastic stromal cells, in solid and hematological tumors.
Depressive mood disorders and severe, chronic stressful life events (DSM-III-R criteria) were more frequently diagnosed in 106 breast cancer patients with respect to 37 patients with benign breast diseases (control group) (p < 0.001), during a stressful period such as hospital admission, diagnosis uncertainty, and when awaiting surgery. The study was performed 5 +/- 3 days before histological diagnosis had been done. Controls showed reduced 24-h diuresis and low catecholamine excretion (norepinephrine, NE; and epinephrine, E) that positively correlated with 24-h diuresis (p < 0.001) and CD3+ lymphocytes (p = 0.056), as during a normal stress response. In contrast, breast cancer patients showed increased 24-h diuresis (with respect to controls p < 0.001) and catecholamine values (p < 0.05). Patients' 24-h diuresis correlated positively with NE (p = 0.02) and 17-ketosteroids (p = 0.004); blood cortisol correlated positively with CD3+ (p = 0.01), CD4+ (p = 0.02), CD8+ (p < 0.01), CD16+ (p = 0.01) lymphocytes and negatively with E (p < 0.03); catecholamines correlated negatively with CD8+ (p = 0.006). These preliminary data are discussed in relation to upregulation of the adrenergic system and the different mechanisms of immune system regulation involved in breast cancer patients, compared with those in subjects with benign breast disease. The differences in these mechanisms may be a result of an imbalance of the bi-directional regulatory circuit of the psycho-neuro-endocrine-immune system, caused by previous life stress or the presence of the tumor mass.
Two cases of unexpected post-partum death of women with acute leukemia are described. In the first case (1st pregnancy) the diagnosis (acute promyelocytic leukemia: M3) was performed one week before delivery and death occurred 3 days later, because of hemorrhagic and renal DIC complication. Since one month before hospitalization, laboratory exams indicated a serious hematological pathology and no further exams were carried out by the physicians, elements of professional fault were recognized in them, considering that because of the diagnostic omission it was impossible to make an early diagnosis and thus perform to specific therapy, adopted only in the terminal phase. This specific therapy is able to determine remission from most cases of acute promyelocytic leukemia. In the second case (2nd pregnancy) the diagnosis (acute myelomonocytic leukemia: M4) was performed only postmortem because, during the whole pregnancy, no signs of disease were evident. After a few hours from the spontaneous delivery, death occurred as a result of an intractable + hemorrhagic syndrome caused by primary hyperfibrinolysis and repeated episodes of cardiac arrest, without possibility of recognizing it. The medical procedures for this case, both throughout pregnancy and terminal phases, appeared free of censure.
The sudden death by hypoglycemia is an aspect of the forensic pathology frequently neglected. Authors initially described the pathogenesis of different hypoglycemia forms, distinguishing the primary ones due to hyperinsulinism and the secondary ones due to functional insufficiency of other organs (hypophysis, thyroid, adrenal gland, liver); after that Authors described three cases of sudden death induced hypoglycemia by hyperinsulinism: two were unweaned with nesidioblastosis and one adolescent. In any form of hypoglycemia the central nervous system damage is present with evident neuronal degenerative-necrotic phenomena, widespread edema with microhemorrhage, swollen and dissociation of myelin sheath, glial cells hyperplasia. Death caused by primary hypoglycemia is histopathologically different from the secondary one because of the maintenance of hepatic glycogen content in the former, that increase in striated muscles, including the heart, in spite of the constant secretion of catecholamine from the adrenal medulla. Glycogen is depleted in secondary hypoglycemia. In the primary form, behind the adrenal medulla hyperfunction, the increased functional activity of the adrenal cortex is moderate, contrasting with the seriousness of the syndrome, due prevalently to inhibit the gluconeogenesis response conditioned by the persistence of stored glycogen in the liver, heart and striated muscles. The rare anoxic processes coming with resynthesis of hepatic glycogen have to be considered in the differential diagnosis. The primary hypoglycemic death, especially in unweaned, is frequently promoted by other processes inducing hypoxia (fetal asphyxia outcome, pneumonia, etc.) or worsening the hypoglycemia (hypothyroidism, etc.). The secondary hypoglycemias are characterized by the normality of exocrine pancreas and by organic alterations that cause glycogen depletion from the liver.
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Sera from 74 hepatitis B surface antigen-positive individuals, who presented with acute hepatitis delta virus (HDV) infection which ran a self-limited course in 58 and progressed to chronicity in 16, were tested over time for HDV markers. In self-limited disease the serum pattern varied from early HD-antigenaemia followed by IgM and IgG anti-HD seroconversion, to the appearance of IgM and IgG anti-HD without antigenaemia, or the isolated expression of either the IgM or the IgG antibody. The typical case of IgM anti-HD was transient and appeared with a mean delay of 10-15 days from admission in the different serological subgroups. The IgG antibody usually developed several weeks later during convalescence. In contrast, patients with disease destined to become chronic had a brisk IgM antibody response and IgG anti-HD was detectable with a mean delay of 15 days; generally, the IgM and the IgG antibody persisted over the follow-up time. IgM antibody to HDV is often the only serological test positive in the clinical stage of hepatitis D and repeated testing for this marker is necessary to diagnose acute HDV co-infection. The serological follow-up provides important prognostic information: waning of IgM confirms resolution of HDV infection, persistence predicts chronicity.
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The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each of 70 patients with inflammatory liver disease and at a low titer in one of six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. The IgM antibody persisted in high titer over many years in patients with unremitting or progressive liver disease, but declined or disappeared before the homologous IgG antibody in the patients whose disease improved or resolved. Testing for IgM antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.
Antibody to the hepatitis delta virus (anti-delta) was detected in 112 out of 2487 (5%) individuals fortuitously found to have the hepatitis B surface antigen (HBsAg) in the blood. Liver function was impaired in 38% (43 of 112) of the anti-delta-positive carriers but in only 9% (215 of 2375) of the anti-delta-negative subjects (p less than 0.001). Liver biopsy specimens were obtained from 31 antibody-positive and 97 antibody-negative subjects with impaired liver function. Important histological changes were observed in 61% of the 31 antibody-positive carriers (7 chronic active hepatitis, 4 active cirrhosis, 8 inactive cirrhosis) but in only 19% of the 97 antibody-negative carriers (p less than 0.001). The presence of anti-delta in serum identifies a subpopulation of apparently healthy HBsAg carriers whose risk of underlying liver disease is four times higher than that in the ordinary carrier. The identification of anti-delta in a symptom-free HBsAg carrier with abnormal liver function is thus an indication for a diagnostic liver biopsy.
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We have undertaken a search for autonomously replicating (ARSs) from Kluyveromyces lactis chromosomal DNA able to sustain plasmid replication in K. lactis and in Saccharomyces cerevisiae. The discovery of such sequences might be interesting for the comparison of ARSs from different sources and possibly useful for the construction of multivalent vectors. HindIII fragments from K. lactis chromosomal DNA were inserted in the YIp5 plasmid (lacking an origin of replication) and the resulting chimaeric plasmids were selected for the ability to transform S. cerevisiae. Four plasmids were identified and further analysed. Two contained the same 1.8 kb K. lactis fragment and transformed both K. lactis and S. cerevisiae with the same efficiency and stability, whereas the third transformed only S. cerevisiae and the fourth transformed K. lactis with a higher efficiency than S. cerevisiae. A detailed study was performed on the 1.8 kb fragment which exhibited ARS function in both yeasts. The fragment was subcloned using different restriction enzymes and Bal31 exonuclease. Subclones were tested for ARS function. ARS activities in the two yeasts were localized in the same 100 bp region. Sequencing demonstrated the presence in this region of the dodecanucleotide 5'ATTTATTGTTTT3' differing from the ARS core consensus of S. cerevisiae only by a T insertion. A similar nucleotide sequence is present in the putative replication origin of the 2 mu-like plasmid pKD1 which stably replicates in K. lactis. Homologies with ARSs from S. cerevisiae were also found in the regions flanking the above-mentioned dodecanucleotide.
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