Dihydropyrimidine dehydrogenase deficiency as a cause of fatal 5-Fluorouracil toxicity

5-Fluorouracil (5-FU), in combination with other cytotoxic drugs, is commonly used to treat a variety of cancers. Dihydropyrimidine dehydrogenase (DPD) catalyzes the first catabolic step of the 5-FU degradation pathway, converting 80% of 5-FU to its inactive metabolite. Approximately 0.3% of the population demonstrate complete DPD deficiency, translating to extreme toxicity of 5-FU. Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy.

Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis

Abstract Introduction: Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance. Objective: To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis. Methods: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5) = 1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment. Conclusions: The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels.

Considerações nutricionais para cirurgia plástica em paciente após cirurgia bariátrica / Nutritional considerations for plastic surgery in post-bariatric surgery patients

A cirurgia bariátrica continua a ser o tratamento mais efetivo para obesidade mórbida e a mais associada a outras condições metabólicas tais como diabetes tipo 2, doença refluxo gastroesofágico, e apneia do sono obstrutiva. Na população obesa, deficiências nutricionais comuns incluem vitaminas A, C, D, e B12, folato, tiamina, ferro, ferritina, zinco e selênio. Com a perda de peso ponderal, muitos pacientes podem utilizar o contorno corporal para deformidades. Após perda de peso ponderal seguida de cirurgia bariátrica, os pacientes geralmente desenvolvem deficiência nutricional significante que aumenta o risco de morbidade e mortalidade pós-operatória com quaisquer cirurgias subsequentes. Alguns pacientes requererem avaliação adicional durante a doença, ou quando candidatos eletivos pré-cirurgia, devido a alterações no trato alimentar com objetivo de melhorar os resultados e prevenir complicações devido a deficiências nutricionais.

Bariatric surgery continues to be the most effective treatment for morbid obesity and most other associated metabolic conditions such as type 2 diabetes mellitus, gastroesophageal reflux disease, and obstructive sleep apnea. In the obese population, common nutritional deficiencies include vitamins A, C, D, and B12, folate, thiamine, iron, ferritin, zinc, and selenium. With massive weight loss, many patients may utilize body contouring for deformities. After massive weight loss following bariatric surgery, patients often develop significant nutritional deficiencies that increase the risk of postoperative morbidity and mortality with any subsequent surgeries. Some unique patients will require additional evaluation during illness or when considering elective surgery due to alterations to the alimentary tract, in order to optimize outcomes and prevent complications from nutritional deficiencies.

Metronomic weekly paclitaxel in advanced unresectable esophageal cancer.

CONTEXT: Advanced esophageal cancer is aggressive with an expected median survival of 6‑7 months. Combination chemotherapy regimens provide effective palliation, but result in substantial toxicity. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients with advanced esophageal cancer, not amenable to definitive intent therapy who were treated with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August 2011, 51 patients were included. Median age was 56 years, with a male: female ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and gastroesophageal junction tumors. 65% of the tumors had squamous histology. Performance status was > 2 in 45%. 61% patients had received prior therapy, either definitive or palliative. 51% patients were platinum‑pre‑treated and 29% had received prior 3 weekly paclitaxel. 76% patients had distant metastases. Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients had improvement in dysphagia, with a median time to symptom improvement of 9 days. In 72% patients, the feeding nasogastric tube could be removed. Overall response rate was 49% (complete remission: 4%, partial remission: 45%, stable disease: 13%). Median progression free survival was 4.7 months (confidence interval [95% CI: 3.7‑5.7 months]) and median overall survival was 7.5 months (95% CI: 3.1‑11.8 months). Histopathology, performance status and pre‑treatment albumin significantly affected survival. The most common grade 3/4 toxicities included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%), neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly paclitaxel chemotherapy may provide palliative benefit in advanced unresectable metastatic esophageal cancer with minimal toxicity.

Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer.

CONTEXT: There are limited effective therapeutic options in the relapsed setting for non-small cell lung cancer (NSCLC) or in the first line for platinum‑ineligible patients. AIM: To evaluate the safety and efficacy of a metronomic schedule of paclitaxel administered weekly in relapsed refractory NSCLC or upfront in patients not eligible for platinum‑based chemotherapy. SETTINGS AND DESIGN: Retrospective analysis of a prospectively collected database from the medical oncology department at Tata Memorial Hospital in Mumbai, India. MATERIALS AND METHODS: Patients with recurrent and treatment-naïve platinum-ineligible advanced NSCLC were treated with weekly paclitaxel at 80 mg/m2 with palliative intent. Restaging scans were obtained every two months. Chemotherapy was continued until progressive disease, intolerable side effects, or decision of the patient. STATISTICAL ANALYSIS USED: SPSS version 16 was used for analysis. Simple percentages were used for descriptive statistics. Progression‑free survival (PFS) was calculated from date of start of paclitaxel till the date of progression, change of therapy due to any reason, or death due to any cause. Overall survival (OS) was calculated from date of start of paclitaxel to death. The Kaplan Meier method was used for estimation of survival. RESULTS: There were 37 patients over eight months. The median age was 59 years, with a male‑to‑female ratio of 5:1. Two patients received paclitaxel in the first line, 18 patients in second line, nine in third line, five in fourth line, and three were in fifth line. 73% patients had received prior platinum and 48.6% patients had Eastern Cooperative Oncology Group performance status (ECOG PS) >2. The median number of weekly cycles delivered was 14. The response rate was 35% [complete remission (CR): 2.7%, partial remission (PR): 32.4%, stable disease (SD): 32.4%, progressive disease (PD): 27%], the median PFS was four months, and the estimated median OS was seven months. Chemotherapy was well tolerated. The most frequent grade 3 toxicities included anemia: 8%, neutropenia: 5.4%, and sensory neuropathy: 8%. There were no grade 4 toxicities and no episodes of febrile neutropenia. CONCLUSIONS: Weekly low‑dose continuous metronomic‑type scheduling of paclitaxel is safe and effective for relapsed refractory NSCLC and in the first line in platinum-ineligible patients.

Bacillus Calmette-Guerin lymphadenitis: A 6-year experience in two Saudi hospitals.

Background : The World Health Organization (WHO) has recommended Bacillus Calmette-Guerin (BCG) vaccination as a part of the global expanded program for immunization. Although the BCG vaccine is usually a safe vaccine, a number of complications with lymphadenitis being the most common complication, can occur. Aim : We evaluated the frequency, the clinical presentation and treatment modalities of lymphadenitis after BCG vaccine in Saudi children. Results : A total of 145 patients with BCG lymphadenitis presented between January 2005 and December 2010. In the majority (103) of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 26 (18%) patients, and both the left axillary and supraclavicular lymph nodes were involved in 7 cases (4.8%). A total of 75 patients (65%) were given antituberculous medication. Eight (27%) patients had positive acid-fast bacilli and positive cultures for Mycobacterium bovis. Conclusion : In light of the findings of this study, it would be advisable to administer the BCG vaccine in Saudi Arabia at a time later than at birth, as the younger children are commonly affected.

Estreptomicina: propiedades fisicoquímicas y toxicidad vestibular / Streptomycin, physical and chemical characteristics and vestibular toxicity

Propósito: Los antibióticos aminoglucósidos estreptomicina (STP) y kanamicina (KAN) son tóxicos para las células sensoriales del vestíbulo y de la cóclea, respectivamente. Químicamente están constituidos por estreptidina (STD) un derivado del inositol y dos azúcares, la esteptosa (Stosa) y la N-metilglucosamida (nm-GLUN); sin embargo, en la STP, la STD tiene dos sustituyentes guanidino, los que están ausentes en la KAN. Por lo tanto, se propone estudiar si la vestíbulo-toxicidad específica de la STP se debe a los grupos guanidino. Material y Métodos: Se incubaron en vitro, membranas celulares aisladas de los órganos vestibulares, con 3H-espermidina (3H-Spdina), un análogo estructural de la STP. Se midió la capacidad de los siguientes compuestos: STP, STD, KAN, guanidina (GUA) y n-acetilglucosamina (na-GLUN) para desplazarlos específicamente. Resultados: Se encontró que el orden de desplazamiento de la 3HSPdina para esas sustancia era STP=STD KanGUAn-a-GLUN. Conclusiones: Los resultados sugieren fuertemente que la STP debe su especificidad vestibulotóxica, a la presencia de los grupos guanidino en la porción de STD de su molécula, los que interactuarían por sus cargas positivas con estructuras membranales vestibulares relacionadas con la transducción, muy probablemente los cilios sensorios de las células ciliadas vestibulares

Intoxicaciones agudas en pediatría: Hospital Central Universitario "Dr. Antonio María Pineda" Enero 1991-Enero 1992 / Acute poisoning in pediatry that had been attended at \"Dr Antonio María Pineda\" University Central Hospital. January 1991-January 1992

Se estudiaron 2.200 casos de intoxicación agudas que consultaron a la Emergencia Pediátrica del Hospital Central Universitario "Dr. Antonio María Pineda". La intoxicación más frecuente fue la medicamentosa, seguida de los agentes de uso doméstico. La circunstancia predominante fue la accidental. Los lactantes representaron el grupo etario más afectado; en general prodedían del medio urbano. Los escolares estuvieron más afectados por emponzoñamiento ofídico y escorpiónico y procedían generalmente del medio rural. El sexo más afectado fue el masculino. Ciento cuarenta y cuatro (144) pacientes presentaron manifestaciones clínicas severas. El 68,8 por ciento de los casos fueron tratados ambulatoriamente. Se registró una mortalidad del 0,3 por ciento