Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

Immunohistochemical expression of PRAME is a marker of poor prognosis in uveal melanoma: A clinico-pathologic and immunohistochemical study on a series of 85 cases.

PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, first isolated in tumor-reactive T-cell clones from a metastatic melanoma patient. It has been widely studied in skin pathology as an immunohistochemical marker capable of distinguishing between benign nevi and malignant melanomas. PRAME has been found to be also expressed in non-melanocytic tumors, including lung, breast, kidney and ovarian cancer. However, less is known about the diagnostic and/or prognostic role of this protein in uveal melanoma (UM); few studies have reported that PRAME expression seems to give to UM patients an additional metastatic risk beyond the other already-known prognostic parameters. In the present retrospective study, we aimed to correlate PRAME immunoreactivity to other clinico-pathologic features and follow-up data on a large series of 85 cases (45 non-metastasizing and 40 metastasizing tumors) of primary UM. A statistically significant correlation was found between PRAME expression and higher metastatic risk and lower metastasis-free survival. We propose to include PRAME in the immunohistochemical panel of UM as an easily usable marker capable of predicting higher metastatic risk and stratifying patients' outcome.

Ten-month follow-up of patients with covid-19 temporally related multi-system inflammatory syndrome in children: the experience of the children hospital of Palermo.

BACKGROUND: In Sicily, the first wave of COVID-19 showed a low epidemic impact in paediatric population, while the second and the third waves had a higher impact on clinical presentation of COVID-19 in children and a significantly higher severe outcome in patients with multisystem inflammatory syndrome in children (MIS-C), with a frequent life-threatening progression. METHODS: We describe a cohort of 22 Sicilian children (11 M; 11 F; age: 1.4-14 years), presenting with clinical features compatible with MIS-C. Patients with negative swab had a history of recent personal or parental infection. RESULTS: The following diagnostic criteria were detected: fever (100%); cheilitis and/or pharyngeal hyperaemia (86%); latero-cervical lymphadenitis (82%); rash (73%); abdominal pain and/or vomiting and/or diarrhoea (64%); conjunctivitis (64%); hands and feet oedema (18%). 59% showed cardiac involvement (6 pericardial effusion; 8 mitral valve insufficiency; 4 insufficiency of two valves; 3 coronary artery lesions (CAL)). In all the patients, treatment was started within 72 h after the admission, with intravenous immunoglobulins (IVIG) (2 g/Kg/dose), methylprednisolone (2 mg/Kg/day in 73% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 27% of patients). Two patients were treated with enoxaparin. Two patients with shock, were additionally treated with vasoactive drugs, albumin, diuretics. Cardiac involvement evolved into the complete resolution of lesions in most of the patients. All the patients were included in a follow-up, to investigate on clinical outcome and resolution of organ involvement. Cardiac valve insufficiency persisted only in 18% of children, CAL persisted only in 33% of children with coronary involvement, however without the evolution into aneurisms. CONCLUSIONS: The preferred treatment strategy was more aggressive at the diagnosis of MIS-C, to block the cytokine cascade. Most of our patients, in fact, received a first-line treatment with IVIG and steroids. This approach could explain the favourable prognosis, the rapid restoring of cardiac function also in patients with MAS or shock, and the good outcome during the 10 months follow-up in all the patients.

Is There a Role of Warburg Effect in Prostate Cancer Aggressiveness? Analysis of Expression of Enzymes of Lipidic Metabolism by Immunohistochemistry in Prostate Cancer Patients (DIAMOND Study).

Prostate Cancer (PCa) is still ranked as the first cancer in the male population and evidences have suggested an alteration of glycemic and lipidic metabolism that are related to its progression and prognosis. The aim of the study is to investigate associations between enzymes' expression, especially involved in the lipidic pathway, and PCa aggressiveness. We retrospectively analyzed data from 390 patients with PCa or benign prostatic hyperplasia (BPH) at the Department of Urology, University of Catania. Immunohistochemical slides were evaluated for the expression of proteins related to glucose and lipidic metabolism. A total of 286 were affected by PCa while 104 by BPH. We demonstrated that ATP-lyase (odds ratio [OR]: 1.71; p < 0.01), fatty acid synthase (OR: 4.82; p < 0.01), carnitine palmitoyl transferase-1a (OR: 2.27; p < 0.05) were associated with androgen receptor (AR) expression. We found that steaoryl Co-A desaturase expression in PCa patients with total cholesterol ≥ 200 mg/dL was independently associated with ISUP ≥4 (OR: 4.22; p = 0.049). We found that CPT-1a+ was associated with biochemical recurrence (hazard ratio: 1.94; p = 0.03]). Our results support the evidence that the manipulation of lipidic metabolism could serve in the future to contrast PCa progression.

Palmoplantar Psoriasis: A Clinico-Pathologic Study on a Series of 21 Cases with Emphasis on Differential Diagnosis.

Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro's microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed.

Heme Oxygenase-1 Overexpression Promotes Uveal Melanoma Progression and Is Associated with Poor Clinical Outcomes.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. To date, the main strategies to counteract its progression consist of focal radiation on the tumor site and ocular enucleation. Furthermore, many UM patients develop liver metastasis within 10 years following diagnosis, eventually resulting in a poorer prognosis for those patients. Dissecting the molecular mechanism involved in UM progression may lead to identify novel prognostic markers with significative clinical applications. The aim of the present study was to evaluate the role of Heme Oxygenase 1 (HO-1) in regulating UM progression. UM cell lines (92.1) were treated with Hemin (CONC e time), a strong inducer of HO-1, and VP13/47, a selective inhibitor of its enzymatic activity. Interestingly, our results showed an enhanced 92.1 cellular proliferation and wound healing ability following an HO-1 increase, overall unveiling the role played by this protein in tumor progression. Similar results were obtained following treatment with two different CO releasing molecules (CORM-3 and CORM-A1). These results were further confirmed in a clinical setting using our UM cohort. Our results demonstrated an increased median HO-1 expression in metastasizing UM when compared to nonmetastasizing patients. Overall, our results showed that HO-1 derived CO plays a major role in UM progression and HO-1 protein expression may serve as a potential prognostic and therapeutical factor in UM patients.

Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia.

BACKGROUND To date, Coronavirus disease 2019 (COVID-19) remains a global health concern, with fatalities mostly in older age groups with underlying medical conditions, while children are less likely to manifest severe symptoms. CASE REPORT We describe the clinical cases of 2 brothers admitted to our Children's Hospital for persistent fever and cough during the COVID-19 pandemic. Case 1. A 1.5-year-old boy had fever, expiratory dyspnea, desaturation, oxygen saturation 94-96% with O2, and bilateral hissing and crackling rales. His interleukin-6 level in the acute phase of the disease was 100.41 and at the resolution it was 46.2 pg/ml. Treatment with amoxicillin plus clavulanic acid, methylprednisolone, and O2 allowed progressive improvement of clinical conditions and laboratory data. Case 2. A 3-month-old toddler was admitted to our hospital for fever, cough, and tachypnea, which started 2 days before hospitalization. He had fever, cough, conjunctivitis, mucous rhinorrhea, and 99% oxygen saturation on room air. Thorax auscultation showed whistles and buzzes. He had a positive molecular test result from a COVID-19 swab. Interleukin-6 levels during all the phases of the disease were <6.25 pg/ml. The chest X-ray was normal. Treatment with azithromycin and methylprednisolone was followed by progressive improvement of clinical conditions. CONCLUSIONS These cases support the strong correlation between interleukin-6 levels and severe clinical manifestations such as COVID-19 pneumonia, and this marker predicts a more severe clinical outcome in children. Testing serum levels of interleukin-6 in children with COVID-19 could be useful to better understand the outcome of lung damage.

MIS-C and co-infection with P. vivax and P. falciparum in a child: a clinical conundrum.

BACKGROUND: The ongoing Coronavirus Disease 2019 (COVID-19) epidemic represents an unprecedented global health challenge. Many COVID-19 symptoms are similar to symptoms that can occur in other infections. Malaria should always be considered in patients with SARS-CoV-2 infection returning from endemic areas. CASE PRESENTATION: We present the first case of multisystem inflammatory syndrome (MIS-C) and Plasmodium vivax-falciparum and SARS-CoV2 coinfection in children. Despite clearance of parassitaemia and a negative COVID-19 nasopharyngeal PCR, the patient's clinical conditions worsened. The World Health Organization (WHO) criteria were used to make the diagnosis of MIS-C. Treatment with intravenous immunoglobulins and methylprednisolone was effective. CONCLUSIONS: This case emphasizes the importance of considering malaria diagnosis in patients returning from endemic areas, even in the COVID 19 era. Malaria and SARS-CoV2 co-infection may increase the risk of MIS-C, for which early detection is critical for proper management.

A Case of Non-Irradiated Balloon Cell Melanoma of the Choroid: Expanding the Morphological Spectrum of Primary Uveal Melanomas.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and usually has a very poor prognosis. Histologically, UMs have been classified in epithelioid cell type, spindle cell type, and mixed cell type. Balloon cells are large pale cells that contain small, hyperchromatic, central nuclei with vesiculated, clear, and lipid-rich cytoplasm. A balloon cell morphology is infrequently observed in naevi and even less frequently in malignant melanomas of the skin, conjunctiva, ciliary body and choroid. In this regard, UMs that exhibit balloon cell features are generally those previously treated with proton beam irradiation and then enucleated, rather than those that directly underwent primary surgery. To the best of our knowledge, very few cases of primary UM showing extensive balloon cell morphology have been reported in scientific literature to date. We herein present an unusual case of primary UM with diffuse balloon cell changes in a 69-year-old woman.

A 7-Year-Old Boy and a 14-Year-Old Girl Initially Diagnosed with Toxic Shock Syndrome and Tested Positive for SARS-CoV-2 Infection, Supporting a Diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C).

BACKGROUND Multisystem inflammatory syndrome in children (MIS-C) has recently been described in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This report describes 2 children with MIS-C who were initially diagnosed with toxic shock syndrome but who tested positive for SARS-CoV-2 infection on reverse transcription-polymerase chain reaction, supporting the diagnosis of MIS-C. CASE REPORT Case 1. A 7-year-old boy with fever, cough, and dyspnea was treated with oxygen, intravenous immunoglobulin (IVIG) infusion, and methylprednisolone and showed a worsening of clinical conditions, persistent fever, hypotension, and hematological parameters compatible with macrophage activation syndrome (MAS). Three intravenous boluses of methylprednisolone (30 mg/kg/day) were followed by a progressive resolution. Case 2. A 14-year-old girl with syncope, fever, diarrhea, oliguria, and increased creatinine levels required fluid infusion and correction of electrolyte imbalance. The increase of creatine phosphokinase (CPK), myoglobin, troponin, and creatine kinase-MB (CK-MB) was associated with grade I atrioventricular block and pericardial effusion. The patient showed myositis and severe muscular weakness, with hematological parameters compatible with MIS-C. She started IVIG and 3 intravenous boluses of methylprednisolone. However, bradycardia, tachypnea, severe hypotension, loss of consciousness, oliguria, bilateral ground-glass pneumonia, bilateral pleural, and peritoneal effusion, in the absence of thromboembolism, required treatment with furosemide, albumin, and enoxaparin, and was followed by a prompt resolution. CONCLUSIONS These 2 pediatric cases highlight the importance of SARS-CoV-2 testing in all patients with acute symptoms and signs of infection during the COVID-19 pandemic. As new variants of SARS-CoV-2 emerge, cases of MIS-C can become more prevalent, and pediatricians should be aware of diagnostic and management guidelines.

Estudio cadavérico del arco de la vena cefálica / Cadaveric study of the cephalic vein arch

RESUMEN: Dentro de las disfunciones de los angioaccesos, la estenosis del arco de la vena cefálica (AVC) juega un papel significativo. Existen características anatómicas del AVC que explican, en parte, este fenómeno. Todo esto obliga a un conocimiento profundo del AVC y sus principales variantes. Se disecaron 43 (n=43) axilas de cadáveres adultos fijados en solución en base a formol. Se registró: longitud del AVC (LAC), angulación del AVC respecto a la vena cefálica (AAC), tipo de terminación (simple o múltiple), presencia de afluentes y su número. LAC promedio 31,6 mm (rango 17-46 mm); AAC promedio 128,95° (rango 65-165°). En cuanto al tipo de terminación 41 (95,3 %) fueron simples, mientras que 2 casos (4,7 %) fueron de forma múltiple. Respecto a los afluentes, se encontraron en 42 de los casos (90,5 %). Se encontraron válvulas en 27 (62,8 %) de los casos. La longitud promedio del AVC fue de 31,6 mm, se dispuso en la mayoría de los casos en ángulo obtuso, presentando en la mayoría de los casos terminación de tipo simple. Además, en el 90,5 % se encontró afluentes que se agotaban en el AVC y en más de la mitad de los casos se encontraron válvulas. Se discuten las implicancias de estos hallazgos en la génesis de la disfunción de angioaccesos.

SUMMARY: Within the angio access dysfunctions, the stenosis of the cephalic vein arch (AC) has a significant role. There are anatomical characteristics of AVC that partially explain this phenomenon. This requires a deep understanding of AVC and its main variants. 43 axillary regions of formalin-fixed adult cadavers were dissected. For this study, the following were registered: length of the AVC (LAC), angulation of the AVC with respect to the cephalic vein (AAC), type of termination (single or multiple), presence and number of tributaries. LAC average 31.6 mm (range 17-46 mm); AAC average 128,95° (range 65-165°). Regarding the type of termination, 41 (95.3 %) were simple, while 2 cases (4.7 %) were multiple. Tributaries were found in 42 of the cases (90.5 %). Valves were found in 27 (62.8 %) of the cases. The average length of the AVC was 31.6mm. Most cases presented an obtuse angle, and simple termination. In addition, in 90.5 % tributaries were found and in more than half of the cases valves were found. Implications of these findings in the genesis of angioaccess dysfunction are discussed.

Respiratory syncytial virus bronchiolitis and hypertransaminasemia.

Bronchiolitis is the most common disease of the lower respiratory tract occurring in children during their first year of life, becoming the most frequent cause of hospitalization. Although the disease can also be caused by other viruses, more than 70% of bronchiolitis cases are caused by respiratory syncytial virus (RSV). RSV bronchiolitis clinically presents rhinitis, coughing, increased breathing and eating difficulties; the symptoms are usually mild, but in some cases may be so severe as to require hospitalization. Diagnosis is mainly clinical and is based on a thorough medical history and a physical examination. Therapy is substantially of support, and has the aim of ensuring alimentation/hydration and optimal oxygenation. It has been recently noted that RSV infections may cause extra-pulmonary manifestations, including liver problems, as rarely described in the literature. The aim of this paper is to present three cases of RSV bronchiolitis in children with elevated transitory transaminase levels.

Skin manifestations of POEMS and AESOP syndrome in the same patient revealing plasma cell dyscrasia.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin signs) and AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndromes are rare paraneoplastic conditions due to an underlying plasma cell dyscrasia. We report a 70-year-old patient with the rare coexistence of POEMS and AESOP syndromes and in whom skin signs, that differ both clinically and histologically, were the clues to the diagnosis of a plasma cell disorder. Vascular endothelial growth factor-A overexpression seems to be the common pathogenetic link of the different clinicopathological presentations of the skin lesions.

Intestinal tuberculosis in a child living in a country with a low incidence of tuberculosis: a case report.

BACKGROUND: Relatively common in adults, intestinal tuberculosis is considered rare in children and adolescents. The protean manifestations of intestinal tuberculosis mean that the diagnosis is often delayed (sometimes even for years), thus leading to increased mortality and unnecessary surgery. The main diagnostic dilemma is to differentiate intestinal tuberculosis and Crohn's disease because a misdiagnosis can have dramatic consequences. CASE PRESENTATION: A 13-year-old Caucasian, Italian female adolescent attended the Emergency Department complaining of abdominal pain, a fever of up to 38 °C, night sweats, diarrhea with blood in stool, and a weight loss of about three kilograms over the previous two months. Physical examination revealed a marked skin pallor and considerable abdominal distension with relevant discomfort in all the abdominal quadrant. Laboratory tests revealed a decreased white blood cell count with anemia and increased C-reactive protein levels. The Mantoux tuberculin skin test was negative. A chest X-ray and an abdominal ultrasonography did not reveal any significant findings. The patient underwent colonoscopy that showed diffuse mucosal congestion and significant blood loss, and laparatomy showed small bowel and colon loops with a whitish appearance. A biopsy of the ileal mucosa revealed inflammation with noncaseating granulomas possibly due to bacterial infection. Given the suspicion of an opportunistic bacterial infection in a child with chronic inflammatory bowel disease (possibly Crohn's disease), treatment with a third-generation cephalosporin was started. However, the abdominal pain, fever and poor general condition persisted and so, after 11 days, the patient underwent total body computed tomography and magnetic resonance imaging of the brain. On the basis of the radiological findings, miliary tuberculosis was suspected and bronchoscopy was performed and resulted positive for Mycobacterium tuberculosis. Miliary tuberculosis was confirmed and an effective treatment with four drugs was started. CONCLUSION: This case shows that the manifestations of intestinal tuberculosis can be very difficult to diagnose and mimic those of Chron's disease. Total body computed tomography and laparotomy with an intestinal biopsy for the detection of Mycobacterium tuberculosis are the means of avoid the risks of a misdiagnosis in children with unexplained chronic abdominal problems.

[Neonatal osteomyelitis of the talus due to methicillin-resistant Staphylococcus epidermidis]. / Osteomielite neonatale dell'astragalo dovuta a Staphylococcus epidermidis meticillino-resistente.

Acute osteomyelitis is a relatively rare disorder in the neonatal period, with considerable morbidity and mortality. Early diagnosis and prompt treatment are essential for a successful outcome. In this report we present a case of acute osteomyelitis of the talus due to methicillin-resistant Staphylococcus epidermidis, observed in a 30-day-old infant.

Acute pancreatitis in children and rotavirus infection. Description of a case and minireview.

This report describes a case of acute pancreatitis in a 2-year-old boy following rotavirus gastroenteritis. Its characteristics are analyzed and discussed in the light of another 4 cases of pancreatitis associated with rotavirus infection found through a systematic review of the international literature. None of the five children underwent surgery or was referred to an intensive care unit and all 5 children recovered with normalization of pancreatic enzymes within 5-10 days. The pathogenesis of this rare complication remains unsettled, and its actual incidence may be higher than reported. Although acute pancreatitis associated with rotavirus gastroenteritis seems to be a mild disease, attention must be paid by the pediatrician fearing possible complications. Rotavirus infection should be amended to the differential diagnosis panel of pancreatitis in toddlers.

[Ileocaecal intussusception associated with adenovirus infection: a case report]. / Un caso di invaginazione ileocecale associata ad infezione da adenovirus.

Intestinal intussusception is the invagination of an intestinal segment into another. Childhood intussusception is usually idiopathic, whereas adult intussusception is usually due to a definable intraluminal lesion or to a systemic disease. Although the aetiology of idiopathic forms often remains unclear, there is appreciable evidence to support an indirect role played by certain infectious agents. In this report we present a case of childhood intussusception probably due to adenovirus infection.

Variations of the cAMP levels in fish ovaries: effect of human chorionic gonadotropin in vitro and of haloperidol in vivo

Se ha desarrollado un ensayo para la determinación de la actividad gonodotrópica en peces hembra, basado en la medición de las variaciones de AMPc en ovario, por medio de un método de radiocompetición proteica. Con ovarios de Cichlasoma facetum, se establecieron las condiciones para la inducción in vitro con gonadotrofina coriónica humana (hCG): 1) preincubación en 1 ml de medio a 30MC durante 60 m; 2) incubación en 1 ml de medio con HCG a 30§C durante 60 m. Este esuqema fue usado en ovarios de Betta splendens de 3-4 meses de edad sexualmente maduras. En una serie de experimentos, se determinó que 50 UI o más de hCG por tubo de incubación, producen un aumento significativo de AMPc con respecto a los controles y que la respuesta es dosis dependiente. El efecto de una inyección intraperitoneal de haloperidol, un antagonista de la dopamina, se estudió en hembras Betta splendens de 3-4 meses de edad sexualmente maduras. Con bajas dosis se observó una tendencia al aumento de AMPc (1 microng/gm de peso corporal) y con mayores dosis (10 microng/gm de peso corporal) hubo un aumento significativo luego de 6 h de la administración. No se observó respuesta a las 24 h. Este trabajo muestra que, como en otros teleósteos, la dopamina actúa como un factor inhibidor de la liberación de gonadotrofina hipofisaria (GRIF) en B. splendens, dado que la admistración de haloperidos induce un aumento de la actividad gonadotrópica

Variations of the cAMP levels in fish ovaries: effect of human chorionic gonadotropin in vitro and of haloperidol in vivo

Se ha desarrollado un ensayo para la determinación de la actividad gonodotrópica en peces hembra, basado en la medición de las variaciones de AMPc en ovario, por medio de un método de radiocompetición proteica. Con ovarios de Cichlasoma facetum, se establecieron las condiciones para la inducción in vitro con gonadotrofina coriónica humana (hCG): 1) preincubación en 1 ml de medio a 30MC durante 60 m; 2) incubación en 1 ml de medio con HCG a 30ºC durante 60 m. Este esuqema fue usado en ovarios de Betta splendens de 3-4 meses de edad sexualmente maduras. En una serie de experimentos, se determinó que 50 UI o más de hCG por tubo de incubación, producen un aumento significativo de AMPc con respecto a los controles y que la respuesta es dosis dependiente. El efecto de una inyección intraperitoneal de haloperidol, un antagonista de la dopamina, se estudió en hembras Betta splendens de 3-4 meses de edad sexualmente maduras. Con bajas dosis se observó una tendencia al aumento de AMPc (1 microng/gm de peso corporal) y con mayores dosis (10 microng/gm de peso corporal) hubo un aumento significativo luego de 6 h de la administración. No se observó respuesta a las 24 h. Este trabajo muestra que, como en otros teleósteos, la dopamina actúa como un factor inhibidor de la liberación de gonadotrofina hipofisaria (GRIF) en B. splendens, dado que la admistración de haloperidos induce un aumento de la actividad gonadotrópica (AU)