Ventral intermediate nucleus deep brain stimulation for treatment-resistant focal aware motor seizures: illustrative case.

BACKGROUND: Resection of the seizure onset zone (SOZ) is considered the gold standard for treating refractory focal aware seizures (FASs). When resective surgery is unadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT; ANT-DBS) has been the procedure of choice. However, less than half of patients with FASs respond to ANT-DBS. The need for alternative targets to effectively treat FAS is thus evident. OBSERVATIONS: The authors report the case of a 39-year-old woman presenting with pharmaco-resistant focal aware motor seizures, with the SOZ located in the primary motor cortical area. She had previously undergone unsuccessful resection of the left temporoparietal operculum elsewhere. Considering the risk of new resective surgery, she was offered combined ventral intermediate nucleus (Vim)/ANT-DBS. Vim-DBS proved to be superior to ANT-DBS for seizure control (88% vs 32%), although the association of both provided the best results (97%). LESSONS: This is the first report on the use of the Vim as a target of DBS for the treatment of FAS. The excellent results were presumably obtained by modulation of the SOZ through Vim projections to the motor cortex. This opens a completely new avenue for treating FAS: chronic stimulation of specific thalamic nuclei.

Characterization, antimicrobial and cytotoxic activity of polymer blends based on chitosan and fish collagen.

This study aims to produce, characterize, and assess the antimicrobial activity and cytotoxicity of polymer blends based on chitosan (CT) and fish collagen (COL) produced by different precipitation methods. Polymer blends were obtained in alkaline (NaOH), saline (NaCl), and alkaline/saline (NaOH/NaCl) solutions with different CT:COL concentration ratios (20:80, 50:50, and 80:20). The polymer blends were characterized by various physicochemical methods and subsequently evaluated in terms of their in vitro antimicrobial and cytotoxicity activity. In this study, the degree of chitosan deacetylation was 82%. The total hydroxyproline and collagen content in the fish matrix was 47.56 mg. g-1 and 394.75 mg. g-1, respectively. The highest yield was 44% and was obtained for a CT:COL (80:20) blend prepared by precipitation in NaOH. High concentrations of hydroxyproline and collagen in the blends were observed when NaOH precipitation was used. Microbiological analysis revealed that the strains used in this work were sensitive to the biomaterial; this sensitivity was dose-dependent and increased with increasing chitosan concentration in the products. The biocompatibility test showed that the blends did not reduce the viability of fibroblast cells after 48 h of culture. An analysis of the microbiological activity of the all-polymer blends showed a decrease in the values of minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) for S. aureus and P. aeruginosa. The blends showed biocompatibility with NIH-3T3 murine fibroblast cells and demonstrated their potential for use in biomedical applications such as wound healing, implants, and scaffolds.

Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome.

CONTEXT: Although metabolic syndrome has been studied in patients with autonomous cortisol secretion, there are limited data for those with nonfunctioning adrenal incidentaloma (NFAI). OBJECTIVE: To assess metabolic syndrome frequency in NFAI patients and controls without adrenal adenoma according to World Health Organization (WHO), National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and International Diabetes Federation (IDF) criteria. DESIGN: Retrospective and transversal study. PATIENTS: Seventy-four NFAI and 90 controls were evaluated. NFAI diagnosis was established according to current guidelines. The control group was selected based on normal adrenal imaging examinations. MEASUREMENTS: Subjects were categorized by metabolic syndrome presence according to WHO, NCEP-ATP III, AACE/ACE and IDF. RESULTS: Age, gender, ethnicity, body mass index, smoking, menopause, statin and fibrate use were comparable between patients and controls. The frequency of prediabetes, dyslipidaemia and hypertension as well as waist circumference were significantly higher in the NFAI patients compared to the controls. The metabolic syndrome frequency in the NFAI group was significantly higher compared to the normal adrenal group: WHO: 69.2% × 31.0% (P < 0.001); NCEP-ATP III: 81.7% × 44.9% (P < 0.001); AACE/ACE: 77.1% × 31.9% (P < 0.001); IDF: 78.6% × 45.5% (P < 0.001). Logistic regression analysis showed that NFAI was a predictor of metabolic syndrome according to WHO (P = 0.001), NCEP-ATP III (P = 0.005) and AACE/ACE (P = 0.007). CONCLUSIONS: Metabolic syndrome is frequently found in patients with NFAI, and this frequency is higher in NFAI patients than in those with normal adrenal imaging.

The Hydroalcoholic Extract Obtained from Mentha piperita L. Leaves Attenuates Oxidative Stress and Improves Survival in Lipopolysaccharide-Treated Macrophages.

Mentha piperita L. (peppermint) possesses antimicrobial properties, but little is known of its ability to modulate macrophages. Macrophages are essential in bacterial infection control due to their antimicrobial functions and ability to link the innate and adaptive immune responses. We evaluated the effects of the peppermint leaf hydroalcoholic extract (LHAE) on cultured murine peritoneal macrophages stimulated or not with lipopolysaccharide (LPS) in vitro. Vehicle-treated cells were used as controls. The constituents of the extract were also identified. Epicatechin was the major compound detected in the LHAE. LPS-induced macrophage death was reversed by incubation with LHAE (1-30 µg/ml). Higher concentrations of the extract (≥100 µg/ml) decreased macrophage viability (49-57%) in the absence of LPS. LHAE (1-300 µg/ml) attenuated H2O2 (34.6-53.4%) but not nitric oxide production by these cells. At similar concentrations, the extract increased the activity of superoxide dismutase (15.3-63.5-fold) and glutathione peroxidase (34.4-73.6-fold) in LPS-treated macrophages. Only LPS-unstimulated macrophages presented enhanced phagocytosis (3.6-6.6-fold increase) when incubated with LHAE (3-30 µg/ml). Overall, the LHAE obtained from peppermint modulates macrophage-mediated inflammatory responses, by stimulating the antioxidant pathway in these cells. These effects may be beneficial when the excessive activation of macrophages contributes to tissue damage during infectious disease.

The presence of nonfunctioning adrenal incidentalomas increases arterial hypertension frequency and severity, and is associated with cortisol levels after dexamethasone suppression test.

There are limited data regarding the frequency of hypertension in nonfunctioning adrenal incidentaloma (NFAI). Our objectives were to investigate rates of hypertension and resistant hypertension in NFAI patients, and compare them to a control group without adrenal adenoma. We also aimed to evaluate the relationship between cortisol levels after 1 mg-dexamethasone suppression test (DST) and hypertension in NFAI patients. We selected 40 patients with NFAI and 40 control patients over the age of 18 without adrenal lesions on abdominal imaging. Data regarding hypertension, resistant hypertension, number, and type of antihypertensive drugs were collected from each subject. Blood samples for C-reactive protein (CRP), plasma adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were also collected from the patients. Age, gender, race, smoking status, menopause status and BMI were comparable between patient and control groups. Patients with NFAI had a higher frequency of hypertension (72.5 vs. 47.5%; p = 0.04), resistant hypertension (37.9 vs. 11.1%; p = 0.04) and took three or more antihypertensive drugs (33.3 vs. 5.2%; p = 0.002) when compared to the controls, respectively. NFAI patients with hypertension had higher mean cortisol levels after 1 mg-DST when compared to NFAI patients without hypertension (1.3 ± 0.3 vs. 1.0 ± 0.4; p = 0.03, respectively). We found a negative correlation between cortisol levels after 1 mg-DST DHEA-S levels (r = -0.61; p < 0.001) and a positive correlation with CRP levels (r = 0.44; p = 0.02). In conclusion, NFAI patients presented a higher frequency of hypertension, resistant hypertension and used more antihypertensive medications when compared to the control group. We found an association between hypertension in NFAI patients and cortisol levels after 1 mg-DST.

Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities.

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthusdrasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide.

Periodontal profile and radiographic characterization of the jaws in a patient with autosomal dominant osteopetrosis.

Osteopetrosis (OP) comprehends a rare group of conditions, presenting on radiographs increased bone density, deriving from irregularities in osteoclast differentiation or function. In the autosomal dominant osteopetrosis (ADO), some patients stay asymptomatic for some time, or only develop mild symptoms. The dental surgeon is often the first to presuppose the disease during routine imaging examinations, referring the patient to a specialized medical group. Furthermore, osteomyelitis is one of the major OP complications, and should be refrained through frequent dental monitoring. Signals of cortical interruption, sclerotic sequestra or periosteal new bone formation, should be looked for in these patients. Their dental management is complex and procedures encompassing bone tissue, such as implant procedures, tissue regenerations, tooth extractions, maxillofacial surgeries and orthodontic treatments, when elected, should be avoided. This case report describes a case of ADO with a diagnosis of moderate generalized chronic periodontitis, not statistically related to plaque index. This is the first case to describe such a condition, in which the systemic component and the altered bone metabolism seem to be related to the loss of periodontal apparatus, independent of the biofilm. Concerning prevention, we can reinforce the need for frequent dental monitoring to avoid further interventions in those cases. LEARNING POINTS: This paper reports a case in which the systemic component and the altered bone metabolism seem to have been related to the loss of periodontal attachment apparatus, independent of the biofilm.The periodontal damage observed in the OP patient was not related to the dental plaque, which leads us to suggest that the cases of periodontitis in OP patients should be diagnosed as periodontitis as a manifestation of systemic diseases.The periodontitis prevention should be longed for in OP patients thus, we propose that doctors responsible for patients with OP refer them to a dental service as soon as possible and that dentists should be aware of the preventive dentistry value as well as the most appropriate dental management for those cases.

Lactobacillus fermentum ATCC 23271 Displays In vitro Inhibitory Activities against Candida spp.

Lactobacilli are involved in the microbial homeostasis in the female genital tract. Due to the high prevalence of many bacterial diseases of the female genital tract and the resistance of microorganisms to various antimicrobial agents, alternative means to control these infections are necessary. Thus, this study aimed to evaluate the probiotic properties of well-characterized Lactobacillus species, including L. acidophilus (ATCC 4356), L. brevis (ATCC 367), L. delbrueckii ssp. delbrueckii (ATCC 9645), L. fermentum (ATCC 23271), L. paracasei (ATCC 335), L. plantarum (ATCC 8014), and L. rhamnosus (ATCC 9595), against Candida albicans (ATCC 18804), Neisseria gonorrhoeae (ATCC 9826), and Streptococcus agalactiae (ATCC 13813). The probiotic potential was investigated by using the following criteria: (i) adhesion to host epithelial cells and mucus, (ii) biofilm formation, (iii) co-aggregation with bacterial pathogens, (iv) inhibition of pathogen adhesion to mucus and HeLa cells, and (v) antimicrobial activity. Tested lactobacilli adhered to mucin, co-aggregated with all genital microorganisms, and displayed antimicrobial activity. With the exception of L. acidophilus and L. paracasei, they adhered to HeLa cells. However, only L. fermentum produced a moderate biofilm and a higher level of co-aggregation and mucin binding. The displacement assay demonstrated that all Lactobacillus strains inhibit C. albicans binding to mucin (p < 0.001), likely due to the production of substances with antimicrobial activity. Clinical isolates belonging to the most common Candida species associated to vaginal candidiasis were inhibited by L. fermentum. Collectively, our data suggest that L. fermentum ATCC 23271 is a potential probiotic candidate, particularly to complement candidiasis treatment, since presented with the best probiotic profile in comparison with the other tested lactobacilli strains.

Bone Mineral Density and Microarchitecture in Patients With Autosomal Dominant Osteopetrosis: A Report of Two Cases.

The aim of this case study is to describe changes in areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) scan, as well as volumetric bone density and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) in two patients with autosomal dominant osteopetrosis (ADO) and compare with 20 healthy subjects. We describe a 44-year-old male patient with six low-impact fractures since he was age 16 years, and a 32-year-old female patient with four low-impact fractures on her past history. Radiographic changes were typical of ADO. Consistent with the much higher aBMD, total volumetric BMD (average bone density of the whole bone, including trabecular and cortical compartments) at distal radius and tibia (HR-pQCT) was more than twice the mean values found in healthy subjects in both patients. Trabecular number and thickness were higher, leading to an evident increase in trabecular bone volume to tissue volume. Also, an enormous increase in cortical thickness was found. Most important, a great heterogeneity in bone microstructure of the affected patients was evident on HR-pQCT images: islets of very dense bone were interposed with areas with apparent normal density. The increase in aBMD, volumetric BMD, and most indices of trabecular and cortical bone, associated with the great heterogeneity on bone tridimensional microarchitecture, reflect the accumulation of old and fragile bone randomly distributed along the skeleton. These alterations in bone microstructure probably compromise bone quality, which might justify the high prevalence of low-impact fractures in patients with ADO, despite abnormally elevated BMD.

Endocrine abnormalities in ring chromosome 11: a case report and review of the literature.

UNLABELLED: Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that have not yet been reported. A 20-year-old female patient had facial dysmorphism, short stature, psychomotor developmental delays, a ventricular septal defect, and thrombocytopenia. Karyotyping demonstrated RC11 (46,XX,r(11)(p15q25)). This patient presented with clinical features that may be related to Jacobsen syndrome, which is caused by partial deletion of the long arm of chromosome 11. Regarding endocrine abnormalities, our patient presented with precocious puberty followed by severe hirsutism, androgenic alopecia, clitoromegaly, and amenorrhea, which were associated with overweight, type 2 diabetes mellitus (T2DM), and hyperinsulinemia; therefore, this case meets the diagnostic criteria for polycystic ovary syndrome. Endocrine abnormalities are rare in patients with RC11, and the association of RC11 with precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM has not been reported previously. We speculate that gene(s) located on chromosome 11 might be involved in the pathogenesis of these conditions. Despite the rarity of RCs, studies to correlate the genes located on the chromosomes with the phenotypes observed could lead to major advances in the understanding and treatment of more prevalent diseases. LEARNING POINTS: We hypothesize that the endocrine features of precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM might be associated with 11q-syndrome.A karyotype study should be performed in patients with short stature and facial dysmorphism.Early diagnosis and adequate management of these endocrine abnormalities are essential to improve the quality of life of the patient and to prevent other chronic diseases, such as diabetes and its complications.

A Sensitive and Selective Label-Free Electrochemical DNA Biosensor for the Detection of Specific Dengue Virus Serotype 3 Sequences.

Dengue fever is the most prevalent vector-borne disease in the world, with nearly 100 million people infected every year. Early diagnosis and identification of the pathogen are crucial steps for the treatment and for prevention of the disease, mainly in areas where the co-circulation of different serotypes is common, increasing the outcome of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Due to the lack of fast and inexpensive methods available for the identification of dengue serotypes, herein we report the development of an electrochemical DNA biosensor for the detection of sequences of dengue virus serotype 3 (DENV-3). DENV-3 probe was designed using bioinformatics software and differential pulse voltammetry (DPV) was used for electrochemical analysis. The results showed that a 22-m sequence was the best DNA probe for the identification of DENV-3. The optimum concentration of the DNA probe immobilized onto the electrode surface is 500 nM and a low detection limit of the system (3.09 nM). Moreover, this system allows selective detection of DENV-3 sequences in buffer and human serum solutions. Therefore, the application of DNA biosensors for diagnostics at the molecular level may contribute to future advances in the implementation of specific, effective and rapid detection methods for the diagnosis dengue viruses.

Striatal somatotopy and motor responses evoked by acute electrical stimulation of the posterior striatum in rats.

INTRODUCTION/OBJECTIVES: Previous experiments suggest that the striatal sensorimotor territory in rats is located in its dorsolateral region, along the rostrocaudal axis, unlike what has been observed in primates. In the present study, electrical stimulation was performed to investigate the degree of participation of the posterior striatum in its motor territory, its somatotopic organization, and the motor responses evoked by stimulation. METHODS: Twenty-five rats were submitted to stereotactic stimulation of the posterior striatum under general anesthesia, receiving consecutively four different current intensities. The motor responses observed in the different body parts were registered for later comparison. We considered as threshold the smallest of these current intensities able to evoke a motor response. RESULTS: The observed motor responses were qualitatively different for each segment: forepaws: ipsilateral, adduction, and contralateral abduction; hindpaws: ipsilateral, flexion, and contralateral, extension/abduction; trunk, rotation/flexion; and tail, rotation/elevation. High-frequency, small-amplitude distal tremor occurred in the ipsilateral forepaw in 95% of the animals. Progressively larger current intensities were necessary for the induction of motor response in the forepaws, hindpaws, and trunk/tail, in that order. CONCLUSIONS: The results allowed us to infer the following posterior striatal somatotopic organization: forepaws, posterolaterally, being the contralateral medial to the ipsilateral; trunk/tail, anteromedially; and hindpaws, in an intermediate position, being the contralateral posterior to the ipsilateral. It is suggested that the tremor and the other observed motor responses derive from the excitation of striatal projection neurons and that the striatum may play an important role in the genesis of essential tremor.

Electrochemical DNA biosensor for human papillomavirus 16 detection in real samples.

An electrochemical DNA biosensor for human papillomavirus (HPV) 16 detection has been developed. For this proposed biosensor, L-cysteine was first electrodeposited on the gold electrode surface to form L-cysteine film (CYSFILM). Subsequently, HPV16-specific probe was immobilized on the electrode surface with CYSFILM. Electrochemistry measurement was studied by differential pulse voltammetry method (DPV). The measurement was based on the reduction signals of methylene blue (MB) before and after hybridization either between probe and synthetic target or extracted DNA from clinical samples. The effect of probe concentration was analyzed and the best results were seen at 1000 nM. The hybridization detection presented high sensitivity and broad linear response to the synthetic-target concentration comprised between 18.75 nM and 250 nM as well as to a detection limit of 18.13 nM. The performance of this biosensor was also investigated by checking probe-modified electrode hybridization with extracted DNA from samples. The results showed that the biosensor was successfully developed and exhibited high sensitivity and satisfactory selectivity to HPV16. These results allow for the possibility of developing a new portable detection system for HPVs and for providing help in making an effective diagnosis in the early stages of infection.

Electrochemical DNA biosensor for bovine papillomavirus detection using polymeric film on screen-printed electrode.

A new electrochemical DNA biosensor for bovine papillomavirus (BPV) detection that was based on screen-printed electrodes was comprehensively studied by electrochemical methods of cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A BPV probe was immobilised on a working electrode (gold) modified with a polymeric film of poly-L-lysine (PLL) and chitosan. The experimental design was carried out to evaluate the influence of polymers, probe concentration (BPV probe) and immobilisation time on the electrochemical reduction of methylene blue (MB). The polymer poly-L-lysine (PLL), a probe concentration of 1 µM and an immobilisation time of 60 min showed the best result for the BPV probe immobilisation. With the hybridisation of a complementary target sequence (BPV target), the electrochemical signal decreased compared to a BPV probe immobilised on the modified PLL-gold electrode. Viral DNA that was extracted from cattle with papillomatosis also showed a decrease in the MB electrochemical reduction, which suggested that the decreased electrochemical signal corresponded to a bovine papillomavirus infection. The hybridisation specificity experiments further indicated that the biosensor could discriminate the complementary sequence from the non-complementary sequence. Thus, the results showed that the development of analytical devices, such as a biosensor, could assist in the rapid and efficient detection of bovine papillomavirus DNA and help in the prevention and treatment of papillomatosis in cattle.

A importância da função de continência no atendimento de pacientes de quadros graves / The importance of content function in the treatment of patients with severe disorders

É importante a função de continência no atendimento de pacientes de quadros graves. Entretanto, há formas de amar que aparecem de forma idealizada ou de maneira extremamente sádica e perversa. Na psicoterapia com pacientes que necessitam de continente, como os transtornos de pânico e obsessivos-compulsivos, há momentos de desespero, nos quais predominam sentimentos de vazio total, de desinteresse, algo como uma ausência de mente ou uma mente que é incapaz de pensar. Formulou-se, assim, a hipótese, de que esta sensação de ausência de mente, de incapacidade de construir um pensamento, sequer era decorrente de um ataque do paciente à relação analítica, de uma rejeição a qualquer relação que apresentasse ser criativa. São descritos momentos nos quais a terapeuta observou fatos clínicos resultantes do mecanismo de identificação projetiva. Nos transtornos obsessivos- compulsivos ocorre uma dificuldade na fixação da libido e no desenvolvimento da capacidade de amar, a qual foi representada pelos ataques que o paciente fazia à relação terapêutica, nos quais ele expressava o desejo de impedir o desenvolvimento do vínculo transferencial positivo, com medo dos sentimentos de liberdade e de criatividade (AU)

A importância da função de continência no atendimento de pacientes de quadros graves / The importance of content function in the treatment of patients with severe disorders

É importante a função de continência no atendimento de pacientes de quadros graves. Entretanto, há formas de amar que aparecem de forma idealizada ou de maneira extremamente sádica e perversa. Na psicoterapia com pacientes que necessitam de continente, como os transtornos de pânico e obsessivos-compulsivos, há momentos de desespero, nos quais predominam sentimentos de vazio total, de desinteresse, algo como uma ausência de mente ou uma mente que é incapaz de pensar. Formulou-se, assim, a hipótese, de que esta sensação de ausência de mente, de incapacidade de construir um pensamento, sequer era decorrente de um ataque do paciente à relação analítica, de uma rejeição a qualquer relação que apresentasse ser criativa. São descritos momentos nos quais a terapeuta observou fatos clínicos resultantes do mecanismo de identificação projetiva. Nos transtornos obsessivos- compulsivos ocorre uma dificuldade na fixação da libido e no desenvolvimento da capacidade de amar, a qual foi representada pelos ataques que o paciente fazia à relação terapêutica, nos quais ele expressava o desejo de impedir o desenvolvimento do vínculo transferencial positivo, com medo dos sentimentos de liberdade e de criatividade