A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom

Background Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.(AU)

A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom

Abstract Background Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research CONEP) and sanitation (National Health Surveillance Agency ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.

Ingestão proteica na encefalopatia hepática: panorama atual / Protein intake in hepatic encephalopathy: current concepts

Hepatic encephalopathy is a severe complication of cirrhosis and comprises a complexand multifactorial pathophysiology. However, ammonia exchange between different tissues still deserves attention in relation to neurological alterations. Hepatic encephalopathy treatment remains focused on the trigger factor correction and the ammonia formation. Therefore, it was believed that high-proteic diets could lead to hepatic encephalopathy through the accumulation of nitrogen compounds in the gastrointestinal tract, which could increase production and absorption of ammonia.Currently, it is known that proteic restriction is harmful to cirrhotic patients, but it isstill utilized. Malnutrition is highly prevalent among cirrhotic individuals with hepatic encephalopathy, thus indicating a nutritional risk which is clearly related to higher mortality rates. Furthermore, there is an increase in the protein needs of these patients and also a relationship between the loss of lean mass and hyperammonaemia. For these and other factors herein discussed, today's global guidelines recommend the ingestion of higher protein levels for patients with hepatic encephalopathy

A encefalopatia hepática é uma complicação grave da cirrose e envolve uma fisiopatologia complexa e multifatorial. Entretanto, a influência da amônia nos diferentes tecidos ainda merece atenção no que se refere às manifestações neuropatológicas. O tratamento da encefalopatia hepática permanece focado na correção do distúrbio desencadeante e na diminuição da formação da amônia a partir do cólon. Por conta disso, acreditava-se que dietas ricas em proteínas poderiam desencadear a encefalopatia hepática por meio do aporte de nitrogênio no trato gastrointestinal, podendo aumentar a produção e a absorção da amônia. Atualmente, sabe-se que a restrição proteica é prejudicial para portadores de cirrose, embora ainda utilizada. A desnutrição é prevalente entre indivíduos cirróticos com encefalopatia hepática, indicando um estado nutricional de risco que está nitidamente relacionado às maiores taxas de mortalidade. Além disso, há um aumento nas necessidades proteicas desses pacientes e uma relação entre a perda de massa magra e a hiperamoniemia. Com base em tais fatores, os guidelines atuais mundiais recomendam dieta hiperproteica para pacientes com encefalopatia hepática.

Redução do MELD em pacientes na lista de transplante hepático após o uso de aminoácidos de cadeia ramificada: relato de caso / Reduction of MELD in patients on the liver transplant list after using chain amino acids: case report

A cirrose hepática (CH) é uma doença com altas taxas de mortalidade e que apresenta, como único tratamento definitivo, o transplante hepático (TH). Infelizmente, nem todos os pacientes têm acesso ao TH e muitos acabam morrendo ainda na lista de transplante. O uso de aminoácidos de cadeia ramificada (AACR) já é amplamente conhecido como tratamento eficaz para a melhora da qualidade de vida destes pacientes. Neste relato, pela primeira vez, documentou-se uma grande melhora clínica e laboratorial em um paciente após o tratamento com AACR, que permitiu ao paciente sair inclusive da lista de transplante. Além da diminuição do escore MELD, houve reestabilização do peso corporal e melhora da qualidade de vida, documentada pelo questionário SF-36.

Liver cirrhosis (LC) is a disease with high mortality rates and its only definitive treatment is the orthotopic liver transplantation (OLT). Unfortunately, not all patients have access to OLT and many of them end up dying on the transplant waiting list. The use of branched chain amino acids (BCAA) is widely known as an effective treatment for improving the quality of life of these patients. For the first time, in this paper we documented a great improvement of clinical and laboratorial tests of a patient treated with BCAA, which allowed him to be out of the transplant waiting list. In addition to the increase of the MELD score, the patient achieved restabilization of body weight and recovery of the quality of life registered by the SF-36 questionnaire.

Alloxan diabetes alters the tensile strength, morphological and morphometric parameters of abdominal wall healing in rats

To investigate the effects of alloxan diabetes on the abdominal wall healing of rats undergoing laparotomy. METHODS: Ninety-six male Wistar rats weighing between 200 and 300 grams, divided into two groups: non-diabetic group (G1) and another with untreated diabetes (G2). Three months after diabetes induction, the animals underwent a 5cm-long- laparotomy and 5.0 nylon monofilament suture. After the surgery, 12 animals from each group were euthanized on days 4, 14, 21 and 30 corresponding to the moments M1, M2, M3 and M4. In each moment a fragment of the abdominal wall containing the scar was removed for tensile strength measurement, histological and morphometric study. Clinical and biochemical parameters were also analyzed. RESULTS: G2 animals showed parameters compatible with severe diabetes and decreased plasma levels of insulin. The tensile strength in G2 was significantly smaller in M2 and M4, with a tendency to fall in the other two. Through light microscope, diabetic animals showed more difficulty to increase collagen density and contraction. G2 animals showed high cellularity of fibroblasts in later healing moments, with collagen thinning in M2 and M4. CONCLUSION: The abdominal wound healing in untreated diabetic animals was altered and led to a higher incidence of dehiscence and infections.

Comparative study between two techniques of incisional hernia repair with polypropylene mesh in rabbits / Estudo comparativo entre duas técnicas de tratamento da hérnia incisional em coelhos utilizando a tela de polipropileno

PURPOSE: To compare two different incisional hernia repair techniques (repair with a polypropylene mesh reinforcement on the peritonium-aponeurosis versus polypropylene mesh sutured to the borders of the hernial ring as a bridge) in rabbits. METHODS: Incisional hernia was experimentally developed through a 4-cm median incision in 60 rabbits. After 30 days, half of the animals were operated for primary wall closure and placement of a polypropylene mesh reinforcement, while the other half had a polypropylene mesh sutured to the borders of the hernial ring as a bridge. Clinical development, scar breaking strength, as well as gross, microscopic and morphometric parameters were evaluated in all animals 30, 60, and 90 days after repair. RESULTS: No significant differences in breaking strength or histological parameters were observed between groups at any time point studied. No statistical difference regarding complications was detected, although denser and firmer adhesions to the abdominal wall were seen after the mesh was placed as a " bridge" . CONCLUSIONS: No significant differences between the incisional hernia repair techniques assessed were observed regarding breaking strength, and histological and morphometric parameters. The number of complications was similar in both study groups. However, adhesion of abdominal cavity organs to the scar area was much denser after the placement of a mesh to bridge the defect.

OBJETIVO: Comparar duas técnicas de tratamento da hérnia incisional em coelhos utilizando a tela de polipropileno apoiando um reforço peritônio - aponeurótico ou suturada nas bordas do anel herniário 'em ponte" . MÉTODOS: Foram operados 60 coelhos para a produção de hérnia incisional, em uma incisão mediana de 4 centímetros. Após 30 dias, metade dos animais foram operados com o fechamento primário da parede, com colocação de uma tela de polipropileno apoiando o reforço e a outra metade dos animais com a colocação da tela suturada nas bordas do anel herniário " em ponte" . Os animais foram avaliados com 30 (M1), 60 (M2)e 90 (M3) dias de pós-operatório. Os parâmetros analisados foram a evolução clínica, análise da força de ruptura da cicatriz, estudo macroscópico, análise microscópica e morfométrica. RESULTADOS: Não foram observadas diferenças significantes com relação a força de ruptura e estudos histológicos nos dois grupos e vários momentos estudados. Não houve diferença estatística com relação às complicações, embora os animais que receberam a tela " em ponte" tiveram aderências mais firmes e intensas à parede abdominal. CONCLUSÕES: As duas técnicas utilizadas para correção da hérnia incisional em coelhos não mostraram diferenças significantes quanto a força de ruptura, análise histológica e morfométrica. O número de complicações foi semelhante, porém a aderência de órgãos da cavidade abdominal à área de cicatriz foi muito mais intensa no grupo em que a tela foi colocada " em ponte" .

Influência do treinamento na evolução da diálise peritoneal / Influence of training on the progression of peritoneal dialysis

Objetivo: Conhecer a influência do cuidador no treinamento da diálise peritoneal (DP) e no tempo livre de peritonite. Método: Estudo retrospectivo com 38 pacientes prevalentes, atendidos na Diálise Ambulatorial do Hospital das Clínicas/Botucatu, que receberam treinamento para DP pela mesma enfermeira. Avaliaram-se: 1) o responsável pela técnica de diálise (paciente ou cuidador); 2) o treinamento (tempo dispensado e desempenho atingido); 3) o tempo livre de peritonite. Foram realizadas regressão logística e análise de sobrevivência por Kaplan-Meyer. Resultado: A DP foi realizada por umcuidador em 71% (N=27) dos pacientes. Dos diabéticos, 89% (N=16) necessitavam de cuidador e 11% (N=2) realizaram o próprio tratamento (p<0,05); quanto à idade, 26% (N=10) apresentavam mais de 65 anos e, destes, 90% (N=9) tinham o cuidador para DP (p=0,05); dos pacientes provenientes de outras localidades (N=23), 74% (N=17) necessitavam do cuidador (p=0,07). O treinamento foi concluído no tempo médio por 71% (N=27), e 79% (N=30) obtiveram desempenho bom, sem diferenças quanto ao responsável pela técnica. A probabilidade de permanecer livre de peritonite no primeiro ano detratamento foi maior quando o cuidador realizava a DP, sendo 54% para o paciente e 78% para o cuidador (p<0,05). Conclusão: Pacientes com mais de 65 anos e diabéticos necessitaram de cuidador na diálise. No treinamento, tempo dispensado e desempenho atingido não diferiram quanto ao responsável pela técnica. O tempo livre de peritonite foi maior para os pacientes em que a diálise foi realizada por cuidador. O responsável pela diálise (paciente ou cuidador) pode influenciar na evolução da DP.

Objective: To evaluate the influence of the caretaker on the training time of peritoneal dialysis (PD) and peritonitis-free time. Method: Retrospective medical record review of 38 patients receiving PD training from the same nurse at the Dialysis Unit of Botucatu Medical School Hospital. Assessment included: 1) home PD provider (patient or caretaker); 2) training (length and performance achieved); 3) peritonitis-free time. Result: In 71% (N=27) of the cases, PD was performed by a caretaker. Among diabetic patients, 89% (N=16) were supported by a caretaker, and 11 % (N=2) performed their own dialysis (p=0.03); 26% (N=10) were over 65 years of age, with 90% (N=10) of them having a PD caretaker (p=0.05). Among patients from other areas (N=23), 74% (N=17) were supported by a PD caretaker (p=0.07). Training was concluded after the mean time by 71% (N=27) and a good performance level was achieved in 79% (N=30) of the cases with no difference between provider type. The probability of the patient remaining peritonitis-free over the first year was higher when PD was performed by a caretaker (patient= 54%; caretaker = 78%; p<0.05). Conclusion: The presence of caretakers was more frequent among the patients who were over 65 years of age or diabetic. With respect to training, length of time and performance did not differ according to the person responsible for technique. Peritonitis-free time was longer among patients supported by caretakers. The PD provider (patient or caretaker) may influence PD results.

Medicina em notícia: a internet como estímulo ao estudo de temas contemporâneos na área da saúde / Medicine on the news: the internet stimulating the study of contemporary health issues

Objetivo: Este artigo vai descorrer uma atividade acadêmica que resultou no desenvolvimento de um banco de dados com temas da área da saúde, que pode servir como estímulo à educação médica. Métodos: durante o estágio de monitoria no Laboratório de Informática, os alunos do curso médico e de enfermagem foram orientados a selecionar notícias da área de saúde, acompanhados de materiais acadêmicos obtidos na internet que pudessem servir de fonte adicional de estudo ao tema da notícia. Resultados: No período de 15 de setembro 2003 a 30 de janeiro de 2004 foram selecionadas e publicadas 104 notícias. Dessas, 50 foram da área de epidemiologia, 30 de novos tratamentos, 17 de fisiologia ou fisiopatologia, cinco de novos métodos diagnósticos e dois de financiamentos em pesquisa. Todas as notícias selecionadas foram publicadas na forma de banco de dados que pode ser acessado de acordo com palavras-chave ou por especialidade. Conclusões: A presente atividade demonstra o potencial da internet na seleção e publicação de conteúdos digitais que podem servir de estímulo ao desenvolvimento intelectual acadêmico e profissional na área da saúde

Gastric cryptosporidiosis as a clue for the diagnosis of the acquired immunodeficiency syndrome

Cryptosporidium parvum has been detected with increasing frequency in the gastrointestinal tract, but involvement of the stomach is rarely reported. Whenever found in the histologic examination of the gastrointestinal mucosa, it should raise the suspicion of an immunocompromised host. We report a case of Cryptosporidium-associated erosive gastritis in a 64-year-old woman, who was found later to have the acquired immunodeficiency syndrome. Gastroduodenoendoscopy and biopsy of the gastric mucosa played an invaluable role in the diagnosis of cryptosporidiosis and to disclose the underlying immunodeficiency state