When the fever will not stop, stop the pills! A case report

ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

When the fever will not stop, stop the pills! A case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

Differential distribution and biochemical characteristics of hydrolases among developmental stages of Schistosoma mansoni may offer new anti-parasite targets.

Schistosoma mansoni enzymes play important roles in host-parasite interactions and are potential targets for immunological and/or pharmacological attack. The aim of this study was to comparatively assess the presence of hydrolytic activities (phosphatases, glycosidases, aminopeptidases) in soluble (SF) and membrane (MF) fractions from different S. mansoni developmental stages (schistosomula 0 and 3h, juveniles, and adult worms of 28 and 45days-old, respectively), by using simple enzyme-substrate microassays. Our results show and confirm the prominent presence of alkaline phosphatase (AlP) activity in the MF of all the above parasite stages, highlighting also the relevant presence of MF-associated α-mannosidase (α-MAN) activity in juveniles. A soluble AlP activity, together with ß-N-D-acetylglucosaminidase (ß-NAG), and α-MAN activities, was detected in SF of schistosomulum 0h. Soluble ß-NAG, α-MAN, acid phosphatase (AcP), leucin (LAP) and alanine (AAP) aminopeptidase activities were also seen in the SF of the other different developmental stages. This work shows different soluble and membrane-associated hydrolytic capacities in each S. mansoni developmental stage from schistosomula to adults that might be exploitable as potential new targets for immune and/or chemoprophylactic strategies.

Metoclopramida mejora la calidad de la endoscopia digestiva superior en paciente con hemorragia digestiva superior activa / Metoclopramide improves the quality of upper gastrointestinal endoscopy in patients with upper gastrointestinal bleeding

La hemorragia digestiva superior aguda (HDSA), es una causa frecuente de hospitalización, se ha estimado una incidencia de 50 a 150 episodios por 100.000 habitantes por año y está asociada a una morbimortalidad significativa. Datos recientes sugieren que algunas medidas terapéuticas, como el uso endovenoso de la eritromicina y la metoclopramida mejoran la visualización endoscópica en pacientes con HDSA; sin embargo, los estudios al respecto no son concluyentes. Determinar la utili-dad de la metoclopramida endovenosa (EV) en mejorar la calidad de la EDS en pacientes con HDSA, a fin de reducir en los pacientes con sangrado agudo la necesidad de cirugía, el uso de transfusiones sanguíneas, el tiempo de hospitalización y la morbimortalidad. Estudio prospectivo, transversal, aleatorizado, llevado a cabo desde Enero-Mayo 2010 en la unidad de gastroenterología del Hospital Dr. Miguel Pérez Carreño. Fueron incluidos todos los pacientes con evidencia clínica de HDSA, con signos y síntomas de menos de 12 horas de evolución, edad ≥18 años. La población a estudiar se dividió en dos grupos: grupo A pacientes que recibieron 10 mg de metoclopramida EV 30-40 minutos previos al estudio; grupo B no recibió metoclopramida EV y fueron elegidos aleatoriamente. La EDS fue realizada en las primeras 6 horas de la admisión. Los criterios de exclusión fueron: sensibilidad conocida a la metoclopramida, disminución del estado de conciencia (por imposibilidad de fir-mar el consentimiento informado) embarazo o lactancia y lavado gástrico previo. Fueron incluidos un total de 44 pacientes, 25 del sexo masculino y 19 femenino, de los cuales 22 recibieron metoclopramida y 22 pacientes restantes no recibieron ningún procinético previo al estudio endoscópico. En el grupo A, se diagnosticó la etiología del sangrado en la primera endoscopia en 17 pacientes, requiriendo la realización de 2 o más endoscopias en 5 casos. En el grupo B, 12 pacientes fueron diagnosticados en la primera...

Active upper gastrointestinal bleeding (AUGIB) is known as a frecuent cause of admission, is estimated to be 50 to 150 per 100,00 each year and it is associated with a significant mortality. There is evidence that suggest that prompt Upper Digestive Endoscopy (UDE) assessment in patients with upper gastrointestinal bleeding is safe and effective, however, in patients with active or recent bleeding the quality of endoscopic examination may be limited by the presence of clots and residual blood, especially in gastric fundus. Recent data suggest that another therapeutic measures as intravenous erythromycin and metoclopramide improve endoscopic visualization in patients with AUGIB, however, few studies confirm these information. The aim of this study was to determine the utility of intravenous metoclopramide to improve upper digestive endoscopy quality in patients with AUGIB preventing the need for additional endoscopy attempts, surgery, blood transfusions, time of hospitalization and mortality. A transversal, randomized prospective study was developed between January and May 2010 at the Gastroenterology department of Dr. Miguel Pérez Carreño Hospital. All patients with clinical evidence of AUGIB were included; the symptoms must be assessed in the first 12 hours, and all of them must be over 18 year old. The subjects were divided into two groups: group A were people with upper gastrointestinal bleeding who received metoclopramide (10 mg) 30 to 40 minutes before UDE and group B did not receive metoclopramide before UDE. They were randomly chosen and compared. Upper digestive endoscopy was performed within the first six hours of admission. Exclusion criteria were: Known sensitivity or intolerance to metoclopramide, altered state of consciousness, pregnancy, lactancy and previous gastric lavage. There were 44 patients (25 males - 19 females), of which 22 received intravenous metoclopramide. Twenty two patients did not receive promotility agents before the UDE...

Molecular modeling studies of Yersinia pestis dihydrofolate reductase.

Considering the risk represented by plague today as a potential biological warfare agent, we propose cytosolic Yersinia pestis dihydrofolate reductase (YpDHFR) as a new target to the design of selective plague chemotherapy. This enzyme has a low homology with the human enzyme and its crystallographic structure has been recently deposited in the Protein Data Bank (PDB). Comparisons of the docking energies and molecular dynamic behaviors of five known DHFR inhibitors inside a 3D model of YpDHFR (adapted from the crystallographic structure) and human DHFR (HssDHFR), revealed new potential interactions and suggested insights into the design of more potent HssDHFR inhibitors as well as selective inhibitors for YpDHFR.

A combined proteomic and immunologic approach for the analysis of Schistosoma mansoni cercariae and adult worm protein extracts and the detection of one of the vaccine candidates, Sm28GST, from a Venezuelan parasite isolate.

Understanding the mode of Schistosoma mansoni larval invasion and the mechanism of immune evasion utilized by larvae and adult worms is essential for a rational development of vaccines or drugs to prevent or cure the disease. This parasite has a very complex molecular organization in all parasite stages, and identifying the major parasite proteins would give clues to schistosome metabolism and to the interaction of the parasite with the host immune system. Our goal was the evaluation of the protein parasite repertoire using a proteomic approach, and the characterization of protein extracts from two different parasite stages of a Venezuelan isolate, such as cercariae and adult worms, previously performed by other authors in some other strains. A comparison among authors was made. Besides, we aimed to identify different isoforms of one of the vaccine candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and mass spectrometry, and to achieve its immunologic detection using sera from rabbits immunized with synthetic peptides derived from the Sm28GST protein. These techniques allowed the identification of some of the target molecules of the protective immune response that are being evaluated as potential members of a multi-component and multi-stage anti-S. mansoni vaccine and to clarify if the selected peptides induce antibodies that are able to recognize different isoforms of the Sm28GST.

A combined proteomic and immunologic approach for the analysis of Schistosoma mansoni cercariae and adult worm protein extracts and the detection of one of the vaccine candidates, Sm28GST, from a Venezuelan parasite isolate / Aproximación al análisis proteómico e inmunológico de extractos proteicos de cercaria y verme adulto de Schistosoma mansoni y detección de uno de los candidatos a vacuna, Sm28GST, de un aislado venezolano

Understanding the mode of Schistosoma mansoni larval invasion and the mechanism of immune evasion utilized by larvae and adult worms is essential for a rational development of vaccines or drugs to prevent or cure the disease. This parasite has a very complex molecular organization in all parasite stages, and identifying the major parasite proteins would give clues to schistosome metabolism and to the interaction of the parasite with the host immune system. Our goal was the evaluation of the protein parasite repertoire using a proteomic approach, and the characterization of protein extracts from two different parasite stages of a Venezuelan isolate, such as cercariae and adult worms, previously performed by other authors in some other strains. A comparison among authors was made. Besides, we aimed to identify different isoforms of one of the vaccine candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and mass spectrometry, and to achieve its immunologic detection using sera from rabbits immunized with synthetic peptides derived from the Sm28GST protein. These techniques allowed the identification of some of the target molecules of the protective immune response that are being evaluated as potential members of a multi-component and multi-stage anti-S. mansoni vaccine and to clarify if the selected peptides induce antibodies that are able to recognize different isoforms of the Sm28GST.

Es esencial comprender la forma como las larvas de Schistosoma mansoni invaden y los mecanismos de evasión inmune utilizados por larvas y adultos, para el desarrollo racional de vacunas o drogas para prevenir o curar la esquistosomiasis. Este parásito tiene una organización molecular muy compleja en todos sus estadíos, por lo que la identificación de las proteínas más importantes es clave para investigar el metabolismo del esquistosoma y la interacción del parásito con el sistema inmune del hospedero. El objetivo de este trabajo fue evaluar el repertorio proteico del parásito utilizando una aproximación proteómica y la caracterización de extractos proteicos de dos estadios parasitarios diferentes de un aislado venezolano, como la cercaria y el verme adulto, previamente realizado por otros autores en otras aislados. Se realizó una comparación entre autores. Además, se identificaron diferentes isoformas de uno de los candidatos a vacuna, la glutation S transferasa (Sm28GST) por 2D SDS-PAGE y espectrometría de masas y se logró su detección inmunológica, usando sueros de conejos inmunizados con péptidos sintéticos derivados de la proteína Sm28GST. Estas técnicas permitieron identificar algunas de las moléculas blanco de la respuesta inmune protectora que están siendo evaluados como miembros potenciales de una vacuna multi-estadio y multi-componente y aclarar si los péptidos seleccionados indujeron anticuerpos capaces de reconocer diferentes isoformas de la Sm28GST.

Sjögren's Syndrome: a literature review / Síndrome de Sjögren: uma revisão da literatura

Sjögren's Syndrome (SS) is a chronic inflammatory systemic disease. It is auto-immune in nature and likely has a multifactorial etiology. This disease is characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands. The disease causes dysfunction and structural damage leading to the classic SS symptoms of xerophthalmia and xerostomia. No clinical findings or immunological markers have yet been accepted as defining a diagnosis of SS or to identify periods of disease activity and remission. It is important that a patient suspected to have SS is evaluated by multidisciplinary teams consisting of ophthalmologists, rheumatologists, otolaryngologists and dentists, among other professionals. Among the clinical manifestations of SS is a notable reduction in salivary flow. Therefore, it is essential that the dentist knows the clinical characteristics, diagnostic methods and treatments for SS. Patients should be properly guided, and preventive measures must be introduced in order to prevent tissue damage, which may arise due to the decrease in salivary flow. This disease affects the individual not only physically but also emotionally and socially, and dentists and health professionals in general must diagnose the disease and apply a therapy in order to provide the best quality of life for their patients.

A Síndrome de Sjögren (SS) é uma doença sistêmica inflamatória crônica, tem uma natureza auto-imune e etiologia provavelmente multifatorial. É uma doença caracterizada por infiltração linfocitária nas glândulas exócrinas. As glândulas lacrimais e salivares são os principais órgãos afetados originando disfunções e prejuízos estruturais que desencadeiam um quadro clássico de xeroftalmia e xerostomia. Nenhum sinal, achado clínico ou imunomarcador descrito até o momento é aceito isoladamente para determinar um diagnóstico ideal de SS ou detectar os períodos de atividade e remissão da doença. É importante que o paciente com suspeita de SS seja avaliado por equipes multidisciplinares compostas por oftalmologistas, reumatologistas, otorrinolaringologistas e dentistas, entre outros profissionais. Entre as manifestações clínicas, salienta-se a acentuada diminuição do fluxo salivar. Portanto, é imprescindível que o dentista conheça as características clínicas, os métodos de diagnóstico e o seu tratamento. Os pacientes devem ser adequadamente orientados, devendo ser introduzidas medidas preventivas para evitar lesões dos tecidos que possam surgir devido à diminuição do fluxo salivar. A doença compromete o indivíduo não só física, mas também emocional e socialmente, cabendo aos dentistas e demais profissionais de saúde a tarefa de diagnosticar e aplicar uma terapêutica para proporcionar uma melhor qualidade de vida aos pacientes.

Informática odontológica: uma disciplina emergente: [revisão] / Dental informatics: an emerging discipline: [review]

Este trabalho de revisão de literatura pretende demonstrar não só a importância da introdução da disciplina de Informática Odontológica no currículo das Faculdades de Odontologia mas também no cotidiano do médico-dentista ou cirurgião-dentista. Nos últimos anos houve um rápido desenvolvimento da Informática aplicada à Odontologia, sobretudo em áreas dedicadas ao exame do paciente, ao diagnóstico e ao plano de tratamento. Os sistemas CAD-CAM, as sondas periodontais computadorizadas, os aparelhos de radiologia digital, as câmaras intra-orais são exemplos da aplicação da Informática em Odontologia. É neste sentido que surge a disciplina de Informática Odontológica, uma área em constante desenvolvimento, que tem por base a aplicação de computadores e ciências de informação para melhorar a prática clínica, a pesquisa, a educação e a gestão. É importante que simultaneamente com a formação em Odontologia haja também adequada formação em Informática Odontológica. Atualmente os avanços tecnológicos e as pesquisas científicas requerem interdisciplinaridade e integração de uma grande quantidade de informação, muitas vezes proveniente de fontes díspares, havendo necessidade de compilar a informação em bases de dados. Os meios informáticos podem aumentar significativamente a velocidade de integração e correlação dessa informação, tornando o diagnóstico médico-odontológico mais rápido e a implementação da terapêutica mais eficaz.

This literature review aimed to present the importance of the discipline of Dental Informatics for the curriculum of dental schools and daily dental practice. In the last years there was a fast development of Informatics applied to Dentistry, especially in areas related to patient exam, diagnosis, and treatment plan. CAD-CAM systems, computerized periodontal probes, digital radiography, and intraoral cameras are examples of the application of Informatics in Dentistry. Dental Informatics is a discipline showing constant development and is based on the application of computers and information science to improve clinical practice, research, education, and management. Therefore, it is important that Dental Informatics is included in the dental curriculum. At present the technological advances and scientific research require interdisciplinary approach and integration of large amount of information. This information usually comes from several sources, which requires its compilation in databases. Informatics media can significantly increase the velocity of integration and correlation of necessary information to speed up the medical-dental diagnosis and improve treatment efficacy.

Detection of Schistosoma mansoni membrane antigens by immunoblot analysis of sera of patients from low-transmission areas.

Schistosoma mansoni surface membrane components play a relevant role in the host-parasite interaction, and some are released in vivo as circulating antigens. n-Butanol extraction favors the release of membrane antigens like alkaline phosphatase, which has been shown to be specifically recognized by antibodies from S. mansoni-infected humans and animals. In the present study, components in the n-butanol extract (BE) of the adult S. mansoni worm membrane fraction were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE [15%]) and further analyzed by immunoblotting (immunoglobulin G) using defined sera. S. mansoni-infected patient sera, but not sera of uninfected patients or sera obtained from patients infected with other parasite species, specifically and variably recognized up to 20 polypeptides in the molecular mass range of approximately 8 to >80 kDa. There were some differences in the number, intensity, and frequency of recognition of the BE antigens among sera from Venezuelan sites of endemicity with a different status of schistosomiasis transmission. Antigens in the 28- to 24-kDa molecular mass range appeared as immunodominants and were recognized by S. mansoni-positive sera from all the sites, with recognition frequencies varying between 57.5 and 97.5%. Immunoblotting with BE membrane antigens resulted in a highly sensitive (98.1%), specific (96.1.0%), and confirmatory test for the immunodiagnosis of schistosomiasis in low-transmission areas.