Neurological manifestations temporally associated with SARS-CoV-2 infection in pediatric patients in Mexico.

PURPOSE: To describe the temporal association of specific acute neurological symptoms in pediatric patients with confirmed SARS-CoV-2 infection between May and August 2020. METHODS: We performed a recollection of all the clinical and laboratory data of patients having acute neurological symptoms temporally associated with SARS-CoV-2 infection at a third-level referral hospital in Mexico City (Instituto Nacional de Pediatría). Patients in an age group of 0-17 years with acute neurological signs (including ascending weakness with areflexia, diminished visual acuity, encephalopathy, ataxia, stroke, or weakness with plasma creatinine kinase (CK) elevation) were evaluated. RESULTS: Out of 23 patients with neurological manifestations, 10 (43%) had a confirmed SARS-CoV-2 infection. Among the infected patients, 5 (50%) were males aged 2-16 years old (median age 11.8 years old). Four (40%) patients confirmed a close contact with a relative positive for SARS-CoV-2, while 6 (60%) cases had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. CONCLUSIONS: Neurological manifestations temporally associated with SARS-CoV-2 infection were noticed in the pediatric population even without respiratory symptoms. In this study, 2 of 6 symptomatic patients had mild respiratory symptoms and 4 had unspecific symptoms. During this pandemic, SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.

Anatomía quirúrgica de la vena tiroidea media: prevalencia en 100 tiroidectomías totales consecutivas / Surgical anatomy of the median thyroid vein: prevalence in 100 consecutive total thyroidectomies

El estudio de las venas tiroideas no ha recibido una investigación tan exhaustiva como lo tuvieron las arterias tiroideas y los nervios laríngeos en relación a la cirugía tiroidea.De los tres pedículos venosos de la glándula tiroides, el medio, de lejos es el menos estudiado. La vena tiroidea media es inconstante y es el primer elemento vascular de la glándula tiroides que debe ser seccionado antes de luxar el lóbulo hacia medial para evaluar sus relaciones posteriores. Su lesión puede provocar sangrado intraoperatorio dificultando secundariamente la identificación del nervio laríngeo inferior y las glándulas paratiroides, próximas a la misma. Se realizó un estudio descriptivo de corte transversal evaluando la pesencia, número, simetría y asociación de la vena tiroidea media con variables tales como edad y sexo del paciente, así como la hiperfuncionalidad de la glándula tiroides y la presencia del tubérculo de Zuckerkandl en 100 tiroidectomías totales llevadas a cabo en el Instituto Nacional del Cáncer y en el Servicio de Otorrinolaringología del Hospital Central del Instituto de Previsión Social del Paraguay. La prevalencia global de vena tiroidea media fue del 74 %. En el lóbulo derecho, la vena se presentó en el 60 %, mientras que en el lóbulo izquierdo en el 53 %. En el 38 % se encontró la vena en ambos lóbulos. En 4 pacientes se localizaron venas tiroideas medias dobles, en una de ellas fue bilateral. El mayor porcentaje de las venas tiroideas medias se originó en el tercio medio del lóbulo, el 72 % en el lado derecho y el 70% en el izquierdo. No se encontró asociación entre la presencia de la vena tiroidea media y la edad, sexo, estado de hiperfunción glandular, así como tampoco con la presencia del tubérculo de Zuckerkandl.

The study of the thyroid veins has not received an investigation as extensive as the thyroid arteries and laryngeal nerves did in relation to thyroid surgery. Of the three veins pedicles of the gland the middle is far the least studied. This vein is inconstant and is the first vascular element of the gland that must be sectioned before the medial lobe is dislocated to evaluate ist posterior relationships. His injury can cause intraoperative bleeding, making it difficult to identify the inferior laryngeal nerve and the parathyroid glands, proximal to it. A descriptive crossseccional study was carried aot evaluating the presence, number, symmetricity and association of the middle thyroid vein with variables such as age and sex of the patient, as well as the hyperfunctionality of the gland and the presence of the Zuckerkandl tubercle in 100 total thyroidectomies undergoing at the National Cancer Institute and the ENT Service of the Social Security Institute´s Central Hospital. The overall prevalence of the middle thyroid vein was 74%. In the right lobe the vein appeared in 60% while in the left lobe in 53 %. Double middle thyroid vein was found in 4 patients, in one of them it was bilateral. The highest percentage of the middle thyroid veins originated in the middle third of the lobe, 72 % on the right and 70% on the left side. No association was found between the presence of the vain and age and sex, the state of glandular hyperfunstion, as well as the presence of Zuckerkandl tubercle.

Metabolism of lysergic acid diethylamide (LSD): an update.

Lysergic acid diethylamide (LSD) is the most potent hallucinogen known and its pharmacological effect results from stimulation of central serotonin receptors (5-HT2). Since LSD is seen as physiologically safe compound with low toxicity, its use in therapeutics has been renewed during the last few years. This review aims to discuss LSD metabolism, by presenting all metabolites as well as clinical and toxicological relevance. LSD is rapidly and extensively metabolized into inactive metabolites; whose detection window is higher than parent compound. The metabolite 2-oxo-3-hydroxy LSD is the major human metabolite, which detection and quantification is important for clinical and forensic toxicology. Indeed, information about LSD pharmacokinetics in humans is limited and for this reason, more research studies are needed.

Aberrant expression of N-glycolyl GM3 ganglioside is associated with the aggressive biological behavior of human sarcomas.

BACKGROUND: The aberrant expression of N-glycolyl GM3 ganglioside (NeuGcGM3) in patients with sarcomas was reevaluated by assessing the relation of this molecule with some clinicopathological features and overall survival (OS) of patients. METHODS: Fifty formalin-fixed and paraffin-embedded specimens from patients diagnosed with sarcomas were included. For the evaluation of NeuGcGM3, the 14F7 monoclonal antibody followed by a peroxidase avidin-biotin system was used. Clinicopathological features were obtained from patient records. Survival rates were estimated by the Kaplan-Meier method and compared with the log-rank test. For multivariate analyses, the Cox regression model was used to identify independent prognostic factors for OS. RESULTS: The majority of samples had high levels of NeuGcGM3 expression (66.0%) that showed statistical correlation with age (p = 0.014), TNM stage (p = 0.022), histological grade (p = 0.013) and proliferation rates (p = 0.012). In addition, a tendency for association with tumor depth (p = 0.070) was evidenced. In univariate survival analysis, TNM stage (p = 0.000), occurrence of metastasis (p = 0.000) and expression of NeuGcGM3 (p = 0.034) were significant prognostic factors for OS, while a tendency for association was evidenced for histological grade (p = 0.091). Among these variables, only the presence of metastasis (p = 0.001) was an independent prognostic factor on multivariate analysis. CONCLUSIONS: The present research suggests the evaluation of NeuGcGM3 expression as a complementary prognostic factor in sarcoma, although our results need to be validated in a larger series and prospective studies. Moreover, our results could support the use of this molecule as a target for immunotherapy.

Chorionic bump in a pregnant patient with a history of infertility.

Chorionic bump is a rare condition in the first trimester of pregnancy. It appears as a bulge from the choriodecidual surface into the gestational sac. So far, there have been no ultrasound or clinical markers that can predict a difference in outcomeWe report a case of a pregnant woman with history of infertility, diagnosed in the first trimester with a chorionic bump. It disappeared spontaneously at 23 weeks of gestation. The pregnancy went well and she delivered a healthy baby.The aetiology and clinical significance of the chorionic bump remains unclear.

Utilización del colgajo muscular en collar del esternocleidomastoideo en el tratamiento quirúrgico del faringostoma. Presentación de un caso y revisión de la literatura / Use of the sternocleidomastoid muscle collar flap in the surgical treatment of the pharyngostoma. Case report and literature review

La fístula faringocutánea se define como una dehiscencia del cierre de la mucosa faríngea, que produce fuga de saliva y comunicación de la luz faríngea con la piel. Puede clasificarse en fístula propiamente dicha, en el que un trayecto fistuloso comunica luz del tubo digestivo con el exterior y en faringostoma en el que la luz de la faringe se abre directamente al exterior con pérdida importante de tejidos blandos. Es una complicación frecuente tras cirugías abiertas de laringe, pudiendo también aparecer tras cirugías de faringe, de columna espinal, reconstrucciones mandibulares así como en cirugías del piso de boca. Si bien pueden cerrar espontáneamente o con tratamiento conservador, muchas de ellas, sobre todo cuando existe una comunicación amplia entre la faringe y la piel, requieren de cirugía. Existen varias técnicas quirúrgicas para cerrar dichas fístulas. Se presenta un caso en el que se realizó la excéresis de un tumor de base de lengua sangrante, incontrolable, con una faringotomía suprahioidea como vía de abordaje, que presentó como complicación postoperatoria una fístula faringocutánea seguida de la formación de un faringostoma amplio. Fue tratado quirúrgicamente con una síntesis del defecto y refuerzo con colgajo muscular en collar con el fascículo esternal bilateral de esternocleidomastoideo. El paciente presentó buena evolución con cierre de la fístula.

Pharyngocutaneous fistula is defined as a dehiscence of the closing of the pharyngeal mucosa, which produces leakage of saliva and communication of pharyngeal light with the skin. It can be classified as a fistula proper, in which a fistulous tract communicates light from the digestive tract with the outside and in a pharyngostoma in which the pharyngeal lumen opens directly to the outside with significant loss of soft tissues. It is a frequent complication after open surgeries of the larynx, and may also appear after surgery of the pharynx, spinal column, mandibular reconstructions as well as surgeries of the floor of the mouth. Although they can close spontaneously or with conservative treatment, many of them, especially when there is a wide communication between the pharynx and the skin, require surgery. There are several surgical techniques to close these fistulas. We present a case in which the excresis of a tongue-based tumor was performed, due to uncontrollable bleeding, with a suprahyoid pharyngotomy as the approach, presenting as a postoperative complication a pharyngocutaneous fistula followed by the formation of a broad pharyngostoma. He was treated surgically with a synthesis of the defect and reinforcement with a muscular flap in a collar with the bilateral sternocleidomastoid sternal fascicle. The patient presented good evolution with closure of the fistula.

Glándula tiroides lingual: diagnóstico y tratamiento / Lingual thyroid gland: diagnosis and treatment

La presencia de glándula tiroidea ectópica es una entidad rara. La tiroides lingual es la ectopía mas frecuente, predominando en mujeres. Este tejido glandular es pasible de sufrir todas las patologías que pueden afectar a la glándula normotópica, pudiendo ser sintomática o asintomática. Se presenta un caso de tiroides lingual en una paciente previamente tiroidectomizada que consultó por disnea y disfagia en la unidad de Cirugía de Cabeza y Cuello del Servicio de Otorrinolaringología del Hospital Central del Instituto de Previsión Social, Asunción, Paraguay. La paciente recibía tratamiento hormonal de reemplazo,mostrando examen funcional normal. La semiología permitió observar un abombamiento de la base de la lengua. La fibroscopía mostró un tumor en base de lengua de unos 3 cm de diámetro, que pudo evaluarse correctamente con una tomografía computada. Ante la sospecha de una tiroides lingual se realizó un centellograma que demostró captación en piso de cavidad oral. Se realizó excéresis tumoral a través de una faringotomía suprahioidea, previa traqueostomía proofiláctica. El informe de Anatomía Patológica confirmó el diagnóstico de bocio coloide ectópico.

The presence of ectopic thyroid gland is a rare entity. The lingual thyroid is the most frequent ectopy, predominating in women. This glandular tissue is capable of suffering all the pathologies that can affect the normotopic gland, being able to be symptomatic or asymptomatic. We present a case of lingual thyroid in a previously thyroidectomized patient who consulted for dyspnea and dysphagia in the Head and Neck Surgery Unit of the Otolaryngology Service of the Central Hospital of the Institute of Social Prevision, Asuncion, Paraguay. The patient received hormone replacement therapy, showing normal functional examination. Semiology allowed to observe a bulging of the base of the tongue. The fibroscopy showed atongue-based tumor about 3 cm in diameter, which could be correctly evaluated with computed tomography.Suspicion of a lingual thyroid was performed with a scintigram demonstrating uptake in the oral cavity floor.Tumor excision was performed through a suprahyoid pharyngotomy, following a prophylactic tracheostomy.The Pathologic Anatomy report confirmed the diagnosis of ectopic colloid goitre.

A comprehensive review of urologic complications in patients with diabetes.

Diabetes Mellitus (DM) is a chronic disease characterized by hyperglycemia, as a result of abnormal insulin production, insulin function, or both. DM is associated with systemic complications, such as infections, neuropathy and angiopathy, which involve the genitourinary tract. The three most significant urologic complications include: bladder cystopathy, sexual dysfunction and urinary tract infections. Almost half of the patients with DM have bladder dysfunction or cystopathy, which can be manifested in women as hypersensitivity (in 39-61% of the diabetic women) or neurogenic bladder. In males it can be experienced as lower urinary tract symptoms (in 25% of diabetic males with a nearly twofold increased risk when seen by age groups). Additionally, an increased prostate volume affects their micturition as well as their urinary tract. Involving sexual dysfunction in women, it includes reduced libido, decreased arousal, clitoral erectile dysfunction and painful or non-sensitive intercourse; and in diabetic males it varies from low libido, ejaculatory abnormalities and erectile dysfunction. Globally, sexual disorders have a prevalence of 18-42%. Erectile dysfunction is ranked as the third most important complication of DM. Urinary tract infections are observed frequently in diabetic patients, and vary from emphysematous infections, Fournier gangrene, staghorn infected lithiasis to repetitive bacterial cystitis. The most frequent finding in diabetic women has been lower urinary tract infections. Because of the high incidence of obesity worldwide and its association with diabetes, it is very important to keep in mind the urologic complication associated with DM in patients, in order to better diagnose and treat this population.

Sertoli-Leydig cell tumor in a 12-year-old girl: a review article and case report.

BACKGROUND: The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. CASE PRESENTATION: A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. CONCLUSIONS: These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.

Rusty pipe syndrome, a cause of bloody nipple discharge: case report.

Breastfeeding has universally known advantages to the mother and child that include nutritional and immunological benefits but also involve reasons of ecological and economic order. Initiation and maintenance of breastfeeding can be associated with common problems. The beginning of milk production may course with bloody nipple discharge, which, after exclusion of pathological entities, concerns a self-resolving physiological syndrome called rusty pipe. We present a case of rusty pipe syndrome and discuss the implications.

HIV behind bars: human immunodeficiency virus cluster analysis and drug resistance in a reference correctional unit from southern Brazil.

People deprived of liberty in prisons are at higher risk of infection by the human immunodeficiency virus (HIV) due to their increased exposure through intravenous drug use, unprotected sexual activity, tattooing in prison and blood exposure in fights and rebellions. Yet, the contribution of intramural HIV transmission to the epidemic is scarcely known, especially in low- and middle-income settings. In this study, we surveyed 1,667 inmates incarcerated at Presídio Central de Porto Alegre, located in southern Brazil, for HIV infection and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667). Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV transmission clusters and drug resistance within the facility with the use of molecular and phylogenetic techniques. The molecular epidemiology of HIV-1 subtypes observed was similar to the one reported for the general population in southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and unique BC recombinants. In particular, the high rate (24%) of URF_BC found here may reflect multiple exposures of the population investigated to HIV infection. We failed to find HIV-infected inmates sharing transmission clusters with each other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high rates of HIV primary and secondary (acquired) drug resistance and an alarming proportion of virologic failure among patients under treatment, unveiling suboptimal access to antiretroviral therapy (ARV), low ARV adherence and dissemination of drug resistant HIV strains in primary infections. Our results call for immediate actions of public authority to implement preventive measures, serological screening and, for HIV-seropositive subjects, clinical and treatment follow-up in order to control HIV infection and limit the spread of drug resistance strains in Brazilian prisons.

NGcGM3/VSSP vaccine as treatment for melanoma patients.

Gangliosides are glycosphingolipids that are present in the plasma membranes of vertebrates and are involved in multiple cellular processes. In the Center of Molecular Immunology an NGcGM3 ganglioside based vaccine has been developed and is conceptualized as a targeted therapy in cancer. NGcGM3/VSSP vaccine had been used as treatment of metastatic melanoma patients and had showed to be safe and immunogenic. The treatment improved antitumoral response or maintain the response obtained with previous onco-specific treatment as chemotherapy. The results indicate that the vaccine improved overall survival of metastatic melanoma patients after first line-chemotherapy. The clinical trial ongoing currently will allow corroborating these results.

Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Primary Lymphoid Tumors and Lymph Node Metastasis.

The reactivity of the 14F7 Mab, a highly specific IgG1 against N-glycolyl GM3 ganglioside (NeuGcGM3) in normal tissues, lymphomas, lymph node metastasis, and other metastatic sites was assessed by immunohistochemistry. In addition, the effect of chemical fixation on the 14F7 Mab staining using monolayers of P3X63Ag.653 cells was also evaluated. Moreover, the ability of 14F7 to bind NeuGcGM3 ganglioside inducing complement-independent cytotoxicity by a flow cytometry-based assay was measured. The 14F7 Mab was reactive in unfixed, 4% paraformaldehyde, 4% formaldehyde, and acetone fixed cells. Postfixation with acetone did not alter the localization of NeuGcGM3, while the staining with 14F7 Mab was significantly eliminated in both cells fixed and postfixed with methanol but only partially reduced with ethanol. The staining with 14F7 Mab was evidenced in the 89.2%, 89.4%, and 88.9% of lymphomas, lymph node metastasis, and other metastatic sites, respectively, but not in normal tissues. The treatment with 14F7 Mab affected both morphology and membrane integrity of P3X63Ag.653 cells. This cytotoxic activity was dose-dependent and ranged from 24.0 to 84.7% (10-1000 µ g/mL) as compared to the negative control. Our data could support the possible use of NeuGcGM3 as target for both active and passive immunotherapy against malignancies expressing this molecule.

Del surgimiento de la psicología humanística a la Psicología humanista-existencial de hoy / From the uprising of humanistic psychology to today ́s humanistic-existential psychology

Este artículo presenta parte de los resultados de la tesis de Maestría: Las teorías de la formación no afirmativas como articulaciones conceptuales entre la Psicología humanista-existencial y la pedagogía crítica. Hace una integración de las bases filosóficas, epistemológicas, antropológicas de la Psicología humanista-existencial. Utiliza metodología de corte cualitativo; la hermenéutica, para comprender e interpretar los autores y construir inferencia teórica.

This article presents a part of the results of the Magister research the non-afirmative formation theories as conceptual articulations between existential-humanistic psychology and the critical pedagogy. It makes an integration of philosophical, epistemological, anthropological fundaments of existential-humanistic psychology. It uses a qualitative methodology: hermeneutic, in order to comprehend and understand authors and to build theoretical inference.

Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma.

NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 µg with five patients included in each dose level except the 900 µg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 µg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose.

Outcomes from ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonist in the context of in vitro fertilization: report of two cases and review of the literature.

OBJECTIVE: To report the outcomes from two cases of ovarian stimulation following the sole administration of gonadotrophin-releasing hormone agonist (GnRHa) in the context of in vitro fertilization (IVF). DESIGN: A case study was conducted. SETTING: National Referral Unit of Reproductive Medicine. PATIENTS: Two infertile women undergoing IVF participated in the study. INTERVENTIONS: Controlled ovarian hyperstimulation using a long protocol. GnRHa (Buserelin) was started in the luteal phase, in a dose of 600 µg/day, for 12 days. MAIN OUTCOME MEASURES: Number of retrieved oocytes, fertilization rate, number of embryos transferred, implantation rate, ongoing pregnancy, and live birth. RESULTS: Both women underwent egg retrieval and transfer of good quality embryos. One of them conceived and recently gave birth to a healthy full-term baby. CONCLUSIONS: The ovarian hyperstimulation after the sole administration of GnRHa is a rare condition. Oocyte retrieval may be a reasonable treatment under these circumstances instead of cycle cancellation. As far as it is known, this is the third case reported of a live birth following the sole administration of GnRHa in the context of IVF.

Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO Foundation study.

PURPOSE: To assess the pharmacodynamic effects of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody with intermediate affinity for the receptor, in skin and tumor tissues from head and neck cancer patients. EXPERIMENTAL DESIGN: Pharmacodynamic study in patients with advanced squamous cell carcinoma of the head and neck, unsuitable for chemoradiotherapy, enrolled in a single-center trial. Patients received 8 weekly infusions of nimotuzumab. The first nimotuzumab infusion was administered 1 week before starting radiation, whereas the remaining doses were administered concomitantly with irradiation. Paired biopsies were taken from skin and primary tumors, before (pretherapy) and 1 week (on single-agent therapy) after first infusion. Immunohistochemistry was conducted to assay the effects of nimotuzumab on total and phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), p-AKT, and proliferation (Ki-67). RESULTS: Nimotuzumab was well tolerated and there was no evidence of skin rash. Objective response was achieved in 9 of 10 patients. The pharmacodynamic assays showed inhibition of p-EGFR in both skin and tumor (P = 0.042 in skin and P = 0.034 in tumor). No significant changes in p-ERK1/2, p-AKT, or Ki-67 were detected in skin. In addition, lymphocytic infiltrates, folliculitis, or perifolliculitis were not observed. In tumor samples, there was an upregulation of p-AKT (P = 0.043), a reduction in proliferation index (P = 0.012), and a nonsignificant trend toward a decrease of p-ERK1/2 (P = 0.091). CONCLUSIONS: The pharmacodynamic data confirmed the ability of nimotuzumab to decrease EGFR phosphorylation. Downstream effects were observed in tumor cells but not in skin, a finding that may help to explain the lack of skin rash in patients treated with nimotuzumab.

Co-existence of integumentary lesions and lung x-ray abnormalities in patients with paracoccidioidomycosis (PCM).

In paracoccidioidomycosis (PCM), the primary lung infection remains silent. In this study, attempts were done to define the primary target organ by correlating lung radiographic abnormalities with the time course of mucosal/skin lesions concurrently exhibited at diagnosis by 63 patients in whom microscopy and/or isolation of Paracoccidioides brasiliensis from respiratory secretions had been positive. Mucosal and skin lesions were found in 65.1% and 12.7% of the patients, respectively. Odynophagia and dysphagia were present in 38.1% each. All patients had lung interstitial infiltrates, and 31.7% had also alveolar lesions; fibrosis was recorded in 46% of them. An inverse correlation was shown for fibrosis and presence of either odynophagia or dysphagia. Cluster analyzes strongly supported two sets of patients: those with mucosal damage, odynophagia/dysphagia, and alveolo-interstitial infiltrates and those with dermal lesions, dyspnea, and lung fibrosis. These groups may represent novel stages in the natural course of PCM.

Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study.

NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues. A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant. Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations. Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy. Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.