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1.
Arq. bras. med. vet. zootec. (Online) ; 69(3): 513-522, jun. 2017. ilus, tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-846834

ABSTRACT

This study aimed to evaluate Himatanthus drasticus latex in a mice wound healing experimental model. Animals were divided into four groups (n=7) according to the treatments: GI - saline 0.9% (control), GII - mineral oil (vehicle), GIII - H. drasticus commercial latex (HdCL) and GIV - H. drasticus mixed isolated fraction (MIF, 1 mg/mL). The treatments were applied topically once daily, 50 µL for 14 consecutive days. Macroscopic lesions were evaluated, considering parameters such as swelling, redness, granulation tissue and reepithelialization. VEGF+, CD68+ expressions and mast cells (Toluidin blue stain) were evaluated. HdCL induced higher contraction and exuberant granulation tissue (P > 0.05). HdCL showed a mild inflammatory process while MIF induced intense infiltrate inflammatory predominantly by lymphocytes, vascular congestion, bleeding and did not presented full reepithelialization. Reorganization of collagen fibers (red picrosirius stain) was observed. CD68+ expression and mast cells were presented as moderate, intense and mild in GI, GIII and GIV, respectively. Neovascularization occurred in all groups, while VEGF+ expression was intense in MIF in relation to HdCL. We concluded that HdCL presents wound healing potential, through modulation of mast cells, CD68+ and VEGF+ expressions that can be associated to triterpenes presence according MIF isolated from HdCL.(AU)


Objetivou-se avaliar o látex de Himatanthus drasticus em feridas induzidas experimentalmente em camundongos. Os animais foram divididos em quatro grupos (n=7): GI - salina 0,9% (controle), GII - óleo mineral (veículo), GIII - látex comercial de H. drasticus (HdCL) e GIV - fração isolada mista de H. drasticus (MIF, 1mg/mL). Os tratamentos foram aplicados topicamente uma vez ao dia (50µL), durante 14 dias consecutivos. Lesões macroscópicas, as expressões de VEGF+, CD68+ e a participação dos mastócitos (coloração azul de toluidina) foram avaliadas. HdCL induziu maior contração e tecido de granulação exuberante (P >0,05). HdCL induziu leve processo inflamatório enquanto MIF promoveu intenso infiltrado inflamatório predominantemente linfocítico, congestão vascular, hemorragia e reepitelização parcial. Observou-se reorganização das fibras colágenas (coloração picrosírius). A expressão de CD68+ e os mastócitos apresentaram-se moderados, intensos e leves em GI, GIII e GIV, respectivamente. A neovascularização foi observada em todos os grupos, enquanto a expressão de VEGF+ foi mais intensa em MIF em relação a HdCL. Conclui-se que HdCL apresenta potencial de cicatrização por meio da modulação dos mastócitos e das expressões de CD68+ e VEGF+, o que pode estar associado à presença de triterpenos de acordo com MIF isolada de HdCL.(AU)


Subject(s)
Animals , Mice , Angiogenesis Inducing Agents/analysis , Apocynaceae/chemistry , Glycoproteins , Mast Cells , Vascular Endothelial Growth Factor A/analysis , Wound Healing/drug effects , Latex/chemistry
3.
Rev Esp Med Nucl Imagen Mol ; 34(6): 345-9, 2015.
Article in English, Spanish | MEDLINE | ID: mdl-25986344

ABSTRACT

OBJECTIVE: To evaluate factors associated with non identification of the sentinel lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the relationship with SLN metastases. MATERIAL AND METHODS: A single-center, cross-sectional and retrospective study was performed. Forty patients with lymphoscintigraphy without sentinel lymph node identification (negative lymphoscintigraphy - NL) were enrolled. The control group included 184 patients with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors were age, body mass index (BMI), tumor size, histology, localization, preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The statistical analysis was performed with uni- and multivariate logistic regression models and matched-pairs analysis. RESULTS: Age (p=0.036) or having BMI (p=0.047) were the only factors significantly associated with NL. Being ≥60 years with a BMI ≥30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking with hookwire seems to increase the likelihood of NL, but demonstrated statistical significance is lacking (p=0.087). The other tested variables did not affect the examination result. When controlling for age, BMI and marking with the harpoon, a significant association between lymph node metastization and NL was not found (p=0.565). CONCLUSIONS: The most important factors related with non identification of SLN in the patients were age, BMI and marking with hook wire. However, only the first two had statistical importance. When these variables were controlled, no association was found between NL and axillary metastases.


Subject(s)
Breast Neoplasms/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Lymphoscintigraphy/methods , Neoplasm Staging/methods , Sentinel Lymph Node/diagnostic imaging , Adult , Aged , Body Mass Index , Cancer Care Facilities , Cross-Sectional Studies , False Negative Reactions , Female , Fiducial Markers , Humans , Middle Aged , Retrospective Studies , Risk Factors , Tertiary Care Centers , Tumor Burden
4.
Chemosphere ; 88(2): 155-60, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22406242

ABSTRACT

The thiadiazolylurea derivative tebuthiuron (TBH) is commonly used as an herbicide even though it is highly toxic to humans. While various processes have been proposed for the removal of organic contaminants of this type from wastewater, electrochemical degradation has shown particular promise. The aim of the present study was to investigate the electrochemical degradation of TBH using anodes comprising boron-doped (5000 and 30,000 ppm) diamond (BDD) films deposited onto Ti substrates operated at current densities in the range 10-200 mA cm(-2). Both anodes removed TBH following a similar pseudo first-order reaction kinetics with k(app) close to 3.2 × 10(-2) min(-1). The maximum mineralization efficiency obtained was 80%. High-pressure liquid chromatography with UV-VIS detection established that both anodes degraded TBH via similar intermediates. Ion chromatography revealed that increasing concentrations of nitrate ions (up to 0.9 ppm) were formed with increasing current density, while the formation of nitrite ions was observed with both anodes at current densities ≥ 150 mA cm(-2). The BDD film prepared at the lower doping level (5000 ppm) was more efficient in degrading TBH than its more highly doped counterpart. This unexpected finding may be explained in terms of the quantity of impurities incorporated into the diamond lattice during chemical vapor deposition.


Subject(s)
Boron/chemistry , Diamond/chemistry , Electrodes , Herbicides/chemistry , Methylurea Compounds/chemistry , Water Pollutants, Chemical/chemistry , Herbicides/analysis , Kinetics , Methylurea Compounds/analysis , Oxidation-Reduction , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/analysis
5.
Transpl Infect Dis ; 14(3): 237-41, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22093046

ABSTRACT

BACKGROUND: Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. METHODS: A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. RESULTS: Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). CONCLUSIONS: YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur.


Subject(s)
Organ Transplantation , Yellow Fever Vaccine/administration & dosage , Yellow Fever/prevention & control , Yellow fever virus/immunology , Adult , Brazil , Female , Humans , Male , Middle Aged , Risk Assessment , Surveys and Questionnaires , Vaccination/methods
7.
Cancer Genet Cytogenet ; 123(1): 55-60, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11120336

ABSTRACT

The relationship between the presence of high frequencies of chromosomal aberrations in peripheral lymphocytes and predisposition to cancer has been suggested for some cancer diseases. In nonfamilial thyroid cancer, the few reports available are equivocal. The aim of this study was to assess the possible chromosomal instability in peripheral blood lymphocytes from 22 patients suffering from nonfamilial thyroid cancer. For this purpose, 2 classic cytogenetic assays, the chromosomal aberrations assay and cytokinesis-blocked micronucleus assay, were chosen. The frequency of chromosomal aberrations excluding gaps (%) was 1.68 +/- 1.39 (mean value +/- SD) for the patients group versus 2.20 +/- 1.87 for the control group. The frequency of binucleated lymphocytes with micronuclei ( per thousand) was 5.41 +/- 3.51 (mean value +/- SD) for the patients group versus 5.37 +/- 3.21 for the control group. The results obtained revealed no significant differences between both groups. The present study reinforces the idea that constitutional chromosomal instability in peripheral blood lymphocytes is not visible in nonfamilial thyroid carcinomas.


Subject(s)
Chromosome Aberrations , Lymphocytes/metabolism , Micronuclei, Chromosome-Defective/metabolism , Thyroid Neoplasms/genetics , Adult , Cell Division/drug effects , Cytochalasin B/pharmacology , Female , Humans , Lymphocytes/drug effects , Lymphocytes/pathology , Male , Micronuclei, Chromosome-Defective/genetics , Micronucleus Tests , Middle Aged , Mitotic Index , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy
8.
Mutagenesis ; 15(1): 69-75, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10640533

ABSTRACT

This study aimed to assess two end-points of DNA damage, namely chromosomal aberrations and micronuclei in peripheral lymphocytes, and their possible relationship with oxidative stress (which may be related to DNA damage and repair) in thyroid cancer patients receiving therapeutic doses of (131)I. Nineteen patients receiving 2590 MBq (70 mCi) were studied. Chromosomal aberrations were scored using standard cytogenetic methods and micronuclei scored in cytokinesis-blocked lymphocytes. Oxidative stress was assessed by determining thiobarbituric acid-reactive substances in blood, total plasma antioxidant status and serum uric acid levels. All parameters were assessed before treatment and 1 and 6 months after (131)I administration. The frequency of micronucleated cells per 1000 binucleated cells scored (mean +/- SEM) increased significantly from 5.21 +/- 0.80 to 9.68 +/- 1.22 1 month after treatment (P < 0.01) and to 8.42 +/- 1.28 6 months after treatment (P < 0.05). The frequency of cells with chromosomal aberrations, excluding gaps, per 100 cells, increased significantly from 1.68 +/- 0.41 to 3.47 +/- 0. 55 1 month after treatment (P < 0.01) and to 4.05 +/- 0.46 6 months after treatment (P < 0.01). Oxidative stress parameters showed slight modifications over the time period studied, but the differences were not significant except for a decrease in thiobarbituric acid-reactive products 6 months after therapy (P < 0. 05) and in serum uric acid concentration 1 and 6 months after therapy (P < 0.01). This report demonstrates slight but significant and persistent DNA damage in (131)I-treated patients as assessed by cytogenetic assays. There was no clear correlation between the cytogenetic findings and oxidative stress parameters studied.


Subject(s)
Chromosome Aberrations , Iodine Radioisotopes/adverse effects , Oxidative Stress , Thyroid Neoplasms/drug therapy , Adult , Aged , Female , Humans , Iodine Radioisotopes/therapeutic use , Lymphocytes/pathology , Lymphocytes/ultrastructure , Male , Micronuclei, Chromosome-Defective/ultrastructure , Middle Aged , Thiobarbituric Acid Reactive Substances , Thyroid Neoplasms/blood , Thyroid Neoplasms/pathology , Uric Acid/metabolism
9.
Clin Cancer Res ; 5(10 Suppl): 3190s-3198s, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10541363

ABSTRACT

The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen x anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40-100 mCi of 131I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003-0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 x 53.4, 29.6 x 35.3, 10.9 x 13.6, and 8.4 x 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.


Subject(s)
Antibodies, Bispecific/therapeutic use , Carcinoma, Medullary/radiotherapy , Haptens/therapeutic use , Iodine Radioisotopes/therapeutic use , Radioimmunotherapy , Thyroid Neoplasms/radiotherapy , Adolescent , Adult , Aged , Antibodies, Anti-Idiotypic/blood , Antibodies, Bispecific/pharmacokinetics , Female , Humans , Male , Middle Aged , Radioimmunotherapy/adverse effects , Radiotherapy Dosage
12.
Eur J Nucl Med ; 18(2): 119-23, 1991.
Article in English | MEDLINE | ID: mdl-2044570

ABSTRACT

The ability of technetium 99m labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in patients with rheumatoid arthritis (RA). Eight patients with clinically active synovitis were injected with 350 MBq 99mTc-IgG, and imaging took place 4 h later. This resulted in excellent images of inflamed synovium. Significant correlations were observed between individual joint uptake on the scan and scores for joint pain (n = 316, p less than 0.001), joint swelling (n = 300, p less than 0.001) or the average of pain and swelling (n = 300, p less than 0.001). These results suggest that 99mTc-IgG scintigraphy may provide an objective, non-invasive test to detect and measure synovitis.


Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Immunoglobulins , Synovitis/diagnostic imaging , Technetium , Humans , Joints/diagnostic imaging , Radionuclide Imaging
13.
Rev Port Cardiol ; 9(1): 41-9, 1990 Jan.
Article in Portuguese | MEDLINE | ID: mdl-2328137

ABSTRACT

AIMS: To study by equilibrium radionuclide angiography (ERNA) the cardiac inotropic reserve after a myocardial infarction, and to evaluate its prognostic value. DESIGN: Patients in a chronic status of a myocardial infarction were studied by ERNA at a basal state and after stimulation with epinephrine, in the same session. Left ventricle (LV) functional abnormalities, global and regional, were evaluated. A 3-to-5 years follow-up was done. PATIENTS AND METHODS: Twenty five patients with a post myocardial infarction were included: 19 with an anterior infarction, 2 with an inferior and 4 with a combined one. All patients had LV dysfunction evaluated by Echocardiogram at hospital discharge. Global and regional LV function were studied by ERNA before and after inotropic stimulation, using increasing doses of epinephrine from 4.8 to 12 micrograms/minute. Heart rate and blood pressure were monitored. ERNA acquisition were done on left oblique best-septal and lateral views, over 400 cardiac cycles, using a Gama-camera GE 400AC. Three groups of patients were considered, according with the change of LV global ejection fraction: increments greater than 2%--group A (positive response); changes between +2% and -2% - group B; decreases greater than 2%--group C (negative response). During a 3 to 5 years follow-up, the incidence of major cardiac events was analysed: cardiovascular mortality, angina, left ventricle failure, myocardial reinfarction and coronary artery by-pass graft surgery. RESULTS: LV global function-Inotropic stimulation was done with an average perfusion time of 30.8 minutes, with total doses of epinephrine between 176 and 660 ng. No significant changes of heart rate (5%) or blood pressure (5.3%) occurred. Basal LV global ejection fraction (EF) was 29.2%. Only 2 patients had a normal LV ejection fraction; 14 patients had a severe LV dysfunction (EF less than 30%) and 9 had a moderate reduction of ejection fraction (EF between 30% and 45%). From the 14 patients with EF less than 30%, twelve had an involvement of the LV anterior wall. After stimulation EF value ineditreased in 9 and decreased in one patient. From the 11 patients with EF greater than 30%, 6 experienced a increase of EF and 3 decreased of EF after stimulation. REGIONAL WALL MOTION: Group A--15 patients--75 segments. In this group 39 segments were related to necrotic ECG localization, and 79% of them contributed to EF increase after stimulation. Forty-one segments were not involved by necrosis, and 78% had a positive contribution to EF increase. Six patients had all LV segments contributing to the EF increase after stimulation. The other 9 patients, had 13 segments not responding to stimulation (EF increments greater than 2%): 5 of them were segments related to ECG site of infarction. Group B--6 patients--30 segments. Five patients had 9 segments with a positive contribution to EF after inotropic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Epinephrine/pharmacology , Myocardial Contraction/drug effects , Myocardial Infarction/physiopathology , Adult , Aged , Chronic Disease , Coronary Disease/physiopathology , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Stimulation, Chemical , Stroke Volume/drug effects
14.
Rev Port Cardiol ; 8(1): 19-26, 1989 Jan.
Article in Portuguese | MEDLINE | ID: mdl-2631811

ABSTRACT

OBJECTIVE: To study the evolution of left ventricular (LV) function in the 1st year after acute myocardial infarction (MI) and to define its prognostic significance. DESIGN: Patients recovering from acute MI submitted to evaluation of LV function by equilibrium radionuclide angiography (RNA) at the time of discharge, three months later and at 12 months of follow-up. PATIENTS AND METHODS: 93 patients suffering an acute transmural MI were submitted to equilibrium RNA. Studies were taken at time of discharge, 3 and 12 months of follow-up. 19 patients had just the 1st study; in 14 the one year follow-up study was not performed. The other 60 include the group submitted to 1 year follow-up. We used the technic of labelled erytrocites in vivo, with acquisition of the blood pool gated with EKG in left lateral. PAGE protocol from GE has been used for processing of images. RESULTS: Mean global ejection fraction (EF) was 20.6 +/- 8.5% for anterior MI with LV failure and 40.2 +/- 14.5% for those without failure; in inferior MI it was 49.9 +/- 12.3% and for combined MI 30.3 +/- 9.5%. The differences between these values are statistically significant. For the 56 patients in which the 1st and 2nd examination were taken we found no significant differences between the mean values for global EF in the 4 groups previously considered. Conversely, we couldn't find a significant difference between the mean EF in the 4 groups, when we compared the values of early (1st and 2nd examinations) test with those of 12 months follow-up. 10 patients (10.8%) died in the 1 year follow-up. All had global EF lower than normal: 33% of deaths in the group with EF less than 20%; 14% in the subset with EF between 20 and 30%; 8% in the sub-group with EF between 30 and 45%. As far as regional motion is concerned we noticed that changes include both the necrotic and the spared areas. We didn't found significant differences between the contribution of necrotic and viable myocardium to the positive or negative variation of global EF, in the 4 groups of infarction considered. Apical segment seems to have an important contribution for global EF changes, both in anterior and inferior MI. CONCLUSION: In this group of patients with acute MI, followed for 12 months, we noticed a higher degree of LV dysfunction in the group of anterior MI. The values of LVEF measured early after the acute attach, usually at hospital discharge are stable along the follow-up, unless major cardiac episodes develop. All the deaths along the one year follow-up had LV dysfunction with EF below 45%. Prognostic "quod vitam" worsened while EF decreased, with a death rate of 33% in the sub-group with global EF less than 20%, and 28% considering those with EF below 30%. In relation with regional motion we found that changes may be elicited both in the necrotic and spared segments. We emphasize the contribution of the apical area to the changes in global EF.


Subject(s)
Gated Blood-Pool Imaging , Myocardial Infarction/physiopathology , Stroke Volume , Adult , Aged , Follow-Up Studies , Humans , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality
15.
Acta Psiquiatr Psicol Am Lat ; 32(4): 271-80, 1986 Dec.
Article in Portuguese | MEDLINE | ID: mdl-3591399

ABSTRACT

A sample of 16 patients with malignant breast tumors were examined by means of an interview, a questionnaire, and the Szondi Test together with a comparison group of 56 patients with benign breast tumors. The patients were divided into two age groups, those below and above 40 years of age. In this way studies done in other countries to investigate the personality structure of cancer patients were replicated. Emphasis was given to the following issues: self-destructive and/or masochistic tendencies, attitudes of depressive resignation, and conflicts with respect to femininity and motherhood. The results showed several significant differences by which benign tumor patients can be better characterized. These patients presented symptoms, experiences and structures of the neurotic type. The cancer patients presented structures closer to the psychosomatic type, with rigid negation of conflicts (in relation to sex, identification, violence and aggression), and with an unreal insertion in the world. Their somatizations are not conversive; they are interpreted as effects of the destructive and violent tendencies which, without release for the lack of adequate contacts with objects, are directed toward themselves. However, this cannot properly be called a masochistic structure because the destructive tendencies do not have a sexual origin, rather they are part of a vehement negation of others and of life itself, in the sense of a primary death drive. It is impossible to tell, however, to what point these characteristics are already the effects of the breast problems, or whether they have more causal relevance as certain previous personal experiences indicate.


Subject(s)
Breast Neoplasms/psychology , Adult , Female , Humans , Interview, Psychological , Middle Aged , Projective Techniques , Surveys and Questionnaires
16.
Acta Psiquiatr. Psicol. Am. Lat ; 32(4): 271-80, 1986 Dec.
Article in Por | BINACIS | ID: bin-52890

ABSTRACT

A sample of 16 patients with malignant breast tumors were examined by means of an interview, a questionnaire, and the Szondi Test together with a comparison group of 56 patients with benign breast tumors. The patients were divided into two age groups, those below and above 40 years of age. In this way studies done in other countries to investigate the personality structure of cancer patients were replicated. Emphasis was given to the following issues: self-destructive and/or masochistic tendencies, attitudes of depressive resignation, and conflicts with respect to femininity and motherhood. The results showed several significant differences by which benign tumor patients can be better characterized. These patients presented symptoms, experiences and structures of the neurotic type. The cancer patients presented structures closer to the psychosomatic type, with rigid negation of conflicts (in relation to sex, identification, violence and aggression), and with an unreal insertion in the world. Their somatizations are not conversive; they are interpreted as effects of the destructive and violent tendencies which, without release for the lack of adequate contacts with objects, are directed toward themselves. However, this cannot properly be called a masochistic structure because the destructive tendencies do not have a sexual origin, rather they are part of a vehement negation of others and of life itself, in the sense of a primary death drive. It is impossible to tell, however, to what point these characteristics are already the effects of the breast problems, or whether they have more causal relevance as certain previous personal experiences indicate.

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