Socioeconomic factors and the probability of death by Covid-19 in Brazil.

BACKGROUND: To design better measures to contain the Covid-19 epidemics, it is relevant to know whether socioeconomic factors are associated with a higher risk of death by Covid-19. This work estimates the effects of individual socioeconomic characteristics on the risk of death by Covid-19. METHODS: Logistic models were estimated to assess the effect of socioeconomic characteristics (income, race/ethnicity, schooling, occupation and economic activity) on the risk of death from Covid-19. For this purpose, Covid-19 individual death records in Rio de Janeiro state, Brazil were combined with the Annual Register of Social Information, which contains socioeconomic information about formal workers. FINDINGS: Workers employed in establishments in the health and public safety sectors present a risk of dying 2.46 and 2.25 times higher than those employed in other activities. Non-white people, men, and those who work in the Metropolitan Region are also more likely to die from Covid-19. People with higher education are 44% less likely to die from the disease. CONCLUSIONS: Some population groups are more vulnerable to the Covid-19 pandemic and individual socioeconomic conditions play a relevant role in the probability of death by the disease. That should be considered in the design of prevention policies to be adopted.

Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy.

Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma.

BACKGROUND: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. METHODS: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. RESULTS: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. CONCLUSION: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process.

PTEN status in advanced colorectal cancer treated with cetuximab.

BACKGROUND: Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway. METHODS: PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab. RESULTS: The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001). CONCLUSION: A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised.

Late miocene tidal deposits in the amazonian foreland basin.

Late Miocene tidal sediments of Acre, Brazilian Amazonia, were deposited in an embayment or interior seaway located in the sub-Andean zone. This late Tertiary embayment system may once have connected the Caribbean with the South Atlantic. The tidal coasts of the embayment-seaway have provided an avenue for the earliest waif (over water) dispersal phases of the great American biotic interchange in the late Miocene. The subsequent change from semimarine to terrestrial environments is of value in assessing the importance of earlier hypotheses on the evolution of the westem Amazonian landscape and gives insight into the formation of several observed biogeographic patterns, especially of aquatic biota.

Metabolic syndrome and biventricular hypertrophy in essential hypertension.

The metabolic syndrome (MS) is associated with structural and functional alterations of the left ventricle (LV); no evidence is available on the impact of the MS on the right ventricle (RV). To assess whether MS, as defined by the ATP III report, is associated with biventricular hypertrophy, a total of 286 hypertensive subjects (mean age 58.7+/-12.2 years) attending our outpatient clinic underwent the following procedures: (1) physical examination and standard clinic blood pressure (BP) measurement; (2) routine laboratory investigations; (3) M-mode, two-dimensional and Doppler echocardiography. LV hypertrophy (LVH) was defined by LM mass index>or=51/47 g m(-2.7) in men and women, respectively. Right-sided chambers were measured in parasternal long axis at the outflow tract and subcostal view; RV hypertrophy (RVH) was defined by anterior RV wall thickness>or=6.0/5.5 mm in men and women, respectively. Filling velocities of both ventricles were assessed by pulsed Doppler echocardiography. Structural cardiac alterations were more pronounced in hypertensive men and women with MS than in their non-MS counterparts and involved both ventricles as shown by the differences in continuous variables as well as in prevalence rates of LVH (58 and 48% vs 28 and 30%, respectively, P<0.01) and RVH (48 and 54% vs 25 and 35%, respectively, P<0.01). Both LV and RV filling in MS hypertensives were more dependent on the atrial systole. Our study shows that in human hypertension, structural and functional cardiac changes induced by MS are not limited to the LV but also involve the right one.

Successful isolation and long-term establishment of a cell line with stem cell-like features from an anaplastic medulloblastoma.

AIMS: Herein we report on the successful isolation and establishment of a novel, long-term, primary, neurosphere-like cell line called 1603-MED from a 5-year-old boy affected by a highly aggressive anaplastic medulloblastoma. METHODS: Elaboration of the new protocol for neurosphere assay is extensively discussed, together with a complete immuno-histochemical and cytogenetic characterization of 1603-MED. RESULTS: Clinical course and histopathology are briefly discussed. The 1603-MED possesses a high capacity for proliferation, CD133 expression, self-renewal and differentiation, thus indicating that anaplastic medulloblastoma contains a subpopulation of cancer stem cells as observed in classic medulloblastoma. CONCLUSIONS: 1603-MED provides us with the first in vitro model of anaplastic medulloblastoma that may be suitable for studying both tumour progression and the genetic mechanisms related to therapy resistance, and may lead to the development and testing of chemosensitivity and new therapeutic targets.

Prevalence and correlates of multiple organ damage in referred treated hypertensives: data from the ETODH study.

This study, carried out in a large cohort of treated essential hypertensives attending an out-patient hospital hypertension clinic, extends previous observations by showing that a clustering of two or three markers of organ damage (OD) has a higher prevalence than a single organ involvement. These findings call for a systematic evaluation of cardiac and extracardiac OD in treated hypertensive patients referred to a specialist setting.

Ambulatory heart rate and target organ damage in never-treated essential hypertensives.

Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (

Epidemiology and clinics of mushroom poisoning in Northern Italy: A 21-year retrospective analysis.

BACKGROUND: Limited information exists about epidemiology and management of mushroom poisoning. We analyzed and described epidemiology, clinical presentation, and clinical course of mushroom-poisoned patients admitted to emergency departments (EDs) of the Province of Parma, Italy. METHODS: Data from the database of mycological service were matched with clinical information retrieved from hospitals' database, from January 1, 1996 to December 31, 2016. RESULTS: Mycologist consultation was obtained in 379/443 identified mushroom poisonings. A remarkable seasonality was found, with significant peak in autumn. Thanks to the collaboration, the implicated species could be identified in 397 cases (89.6%); 108 cases (24.4%) were due to edible mushrooms, Boletus edulis being the most represented (63 cases). Overall, 408 (92%) cases presented with gastrointestinal toxicity. Twenty cases of amatoxin poisoning were recorded (11 Amanita phalloides and 9 Lepiota brunneoincarnata). One liver transplantation was needed. We observed 13 cases of cholinergic toxicity and 2 cases of hallucinogenic toxicity. Finally, 46 cases were due to "mixed" toxicities, and a total of 69 needed hospitalization. CONCLUSIONS: Early identification and management of potentially life-threatening cases is challenging in the ED, so that a mycologist service on call is highly advisable, especially during periods characterized by the highest incidence of poisoning.

Deranged anterior pituitary responsiveness to hypothalamic hormones in depressed patients.

Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders. In ten, TRH, 500 microgram given intravenously, induced a rise in plasma growth hormone (GH) level, while in eight patients it induced a rise in plasma levels of FSH or LH or both. When LH-RH, 150 microgram was administered intravenously to ten patients, it induced a rise in plasma GH level in one patient and increased plasma prolactin level in three patients. Collectively, in only three of 14 patients was conventional AP responsiveness to hypothalamic neurohormones present. These findings demonstrate the existence of a profound derangement of AP responsiveness to hypothalamic neurohormones in depressed patients and suggest that a primary alteration in the physiologic links between the central nervous system and the AP may be at the origin of the neuroendocrine disturbance.

Modulation of hemostatic balance with antithrombin III replacement therapy in a case of liver cirrhosis associated with recurrent venous thrombosis.

Patients with liver failure can present both thrombotic and hemorrhagic complications because of the deficiency in coagulation factors and inhibitors (protein C and S, antithrombin III) and impairment of fibrinolytic balance. Here we report the case of a 63-year-old man with liver cirrhosis, recurrent thrombosis, and features of low-grade consumption coagulopathy, showing severe antithrombin III deficiency (about 30% of normal values). Treatment with antithrombin III (2000 U/day) and low doses of heparin (5000 U b.i.d.) was successful in modulating the coagulation system toward an antithrombotic effect. After discharge from hospital the ambulatory treatment with antithrombin III concentrates (2000 U twice a week) allowed the attainment of antithrombin III activity of about 60% and prevented the patient from recurrence of venous thrombosis.

Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy.

The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found among ER, PR status, and the presence of serum thyroid antibodies. In conclusion, 1) the present study provides evidence that the overall prevalence of thyroid disorders is increased in patients with breast cancer, and 2) thyroid autoimmune disorders, especially Hashimoto's thyroiditis, account to a large extent for the increased prevalence of thyroid disease in patients with breast cancer. This feature is independent from the ER and PR status of the primary tumor. The present findings call attention to the usefulness of screening for thyroid disease in any patient with breast cancer.

3-Methoxy-4-hydroxyphenylglycol and primary depression: clinical and pharmacological considerations.

Pretherapeutic urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was studied in 25 primary depressed patients. The results indicate that: (i) There exists a wide variability among primary depressives with respect to MHPG excretion. (ii) Age of onset together with polarity of the disease may account for the nonhomogeneous division of the patients according to MHPG levels. (iii). The other variables considered, with the possible exception of motor activity, do not explain the dichotomy between high or normal and low MHPG levels, even though it is possible that they influence MHPG excretion to some extent, with the consequent possibility of errors in subclassification of the patients at the boundaries between the two groups. (iv) The correlation between motor retardation and low MHPG excretion is positive, but probably due to a frequent association between this motricity state and primary depression of bipolar early onset type. (v) Treatments with chlorimipramine and, to a lesser degree of specificity, with amitriptyline are particularly indicated in patients with normal or high MHPG. Some practical and theoretical implications deriving from these data are briefly discussed.

Local insulin infusion stimulates expression of plasminogen activator inhibitor-1 and tissue-type plasminogen activator in normal subjects.

PURPOSE: Plasma levels of plasminogen activator inhibitor-1 are increased in obesity, hypertension, and diabetes. Their correlation with insulin levels supports the hypothesis that hypofibrinolysis may affect the development of atherosclerotic complications in patients with insulin resistance. To investigate the effect of insulin on fibrinolysis, we evaluated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) antigens during insulin infusion in the forearm vascular beds of 8 healthy subjects. MATERIALS AND METHODS: Insulin was infused in the brachial artery of each subject to raise local venous concentrations to approximately 100 microU/mL. Blood samples were obtained from the brachial artery and vein at baseline, after 30, 60, 90, and 120 minutes of infusion, and 30 minutes after the end of the infusion. RESULTS: Following intra-arterial infusion of insulin, forearm blood flow (mean +/- SD) increased progressively from 2.7 +/- 0.6 to 4.0 +/- 0.6 mL/dL/min (P <0.01) and did not return to baseline after the end of the infusion. Plasminogen activator inhibitor-1 balance increased (345 +/- 160 versus 8 +/- 152 fmol/dL/min, P <0.02) at 60 minutes, reaching baseline levels after the end of the infusion. After 90 minutes, tPA balance increased (40 +/- 26 versus 7 +/- 29 fmol/dL/min, P <0.01) with a profile similar to forearm blood flow. CONCLUSIONS: Local hyperinsulinemia induces regional vasodilation and expression of PAI-1 and tPA antigens. An alteration of this physiological process could be involved in the development of hypofibrinolysis and atherosclerosis in states of insulin resistance.

Comparison of monoclonal immunocytochemical and immunoenzymatic methods for steroid receptor evaluation in breast cancer.

The production of monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PR) has permitted the development of the enzyme immunoassay (EIA) and immunocytochemical assay (ICA) for steroid receptor determination. The results obtained with these two techniques, using the same monoclonal antibodies, were compared in a large series of breast carcinomas (187 for ER and 100 for PR). The correlation between these methods was significant for ER (rs = 0.54) and PR (rs = 0.55) (P less than 0.001) but was lost when the receptor concentrations determined by EIA were less than or equal to 15 and less than or equal to 30 fmol/mg protein for ER and PR, respectively. When these values are considered as cutoffs, the concordance between the two methods was 84.5% for ER and 73% for PR. An analysis of discordant results revealed that low epithelial cellularity generally was present in ICA-positive, EIA-negative specimens, whereas only focal positivity with ICA, or positivity of only normal peripheral mammary ducts and lobules, frequently was found in ICA-negative, EIA-positive tumors. In conclusion, there is good correlation between the results obtained by EIA and ICA methods for detection of ER and PR. The authors suggest that biochemical and histochemical methods for steroid receptors could be considered complementary and used together for the analysis of breast cancer.

Interference between anti-HLA antibodies and CPZ metabolites.

The interference of chlorpromazine (CPZ) and several preincubated CPZ metabolites on the lymphocyte absorption of antibodies directed against HLA-A1 and other nonrelated HLA specificities were investigated. Both CPZ and metabolites 7-OH-, Nor1-, and Nor2-CPZ were found to interfere with the specific absorption of anti-HLA-A1 antibodies. The meaning of such a result is discussed.

Computerized echocardiographic study of left ventricular function and cardiodynamic investigation with a new antihypertensive agent (indenolol).

Indenolol hydrochloride is a recently introduced antihypertensive substance. Although it has beta-adrenoceptor blocking activity, its action is due to total peripheral resistance reduction. We investigated the effects of indenolol therapy on left ventricular performance in 15 patients with essential hypertension. Assessments were made using systolic time intervals and computerized echocardiography. The echocardiographic and mechanocardiographic tracings were recorded three times: at the beginning of the trial, after seven days of placebo, and after three weeks of indenolol treatment. The indenolol therapy significantly decreased (P less than 0.001) systolic and diastolic blood pressures and heart rate in all patients, both in supine and standing positions. After three weeks of treatment, systolic time intervals and echocardiographic determinants of left ventricular function were substantially unchanged in comparison with the basal and placebo evaluations. We conclude that indenolol exerted a marked effect on chronotropism but no demonstrable negative effect on inotropism in patients with essential hypertension. No clinical signs of heart failure were recorded. Side effects were absent, and patient compliance was good in all cases.

p53 overexpression in lymph node metastases predicts clinical outcome in ductal pancreatic cancer.

In this study, we evaluated the prognostic significance of both p53 overexpression and proliferating activity in 133 primary ductal pancreatic carcinomas and in their regional synchronous lymph node metastases by immunohistochemistry, by using DO7 and MIB1 monoclonal antibodies, respectively. Tumor samples and lymph nodes were obtained from formalin-fixed, paraffin-embedded archival material of patients operated on between 1976 and 1996. Patients had a well-documented clinical history and were given accurate follow-up. p53 accumulation was observed in 77 (54%) of 133 primary tumors and in 22 (44%) of 50 patients with nodal metastases. The p53 overexpression was directly related to proliferating activity (p = 0.01) in the primary tumors. A significant direct correlation was present between the p53 expression in the primary tumor and in nodal metastases (p = 0.01); the same occurred for proliferating activity by MIB1 (p = 0.002). The patients' overall survival was affected by the presence of nodal (p = 0.02) and distant (p = 0.0001) metastases. The p53 immunoreactivity in nodal metastases was associated with a statistically significant decrease in the postoperative survival period (p = 0.005). Multivariate analysis confirmed these results, and the only two parameters that maintained statistical significance were M1 status (p = 0.0006) and p53 overexpression in nodal metastases (p = 0.01).

Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus.

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.