Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.

PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. Materials and METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.     

ROLE OF INTERMEDIARY BIOMARKERS IN DETERMINING THE ANTICANCER EFFICACY OF MARINE COMPOUNDS

In the present study, two of the probable an umor marine compounds, manzamine A and sarcophine, were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells as intermediary biomarker. Briefly, MCF-7 cells were treated with the compounds for 24 h followed by treatment with BP (0.5 μM). After 24h incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by ³²P-postlabeling technique. Manzamine A and sarcophine increased the BP-DNA adducts by 2 to 4-folds. Further, manzamine A (50 μM) substantially down regulated the expression of p53 while sarcophine (50 μM) slightly induced the level of p21. The residual DNA repair ability was almost completely abolished by manzamine A while sarcophine was ineffective. Based on our preliminary results, these compounds may be classified as potential genotoxic.     

白首乌化学成分的研究

自白首乌主要品种耳叶牛皮消(Cynanchum auriculatum Royle ex Wight)根中首次分得三个已知甾体酯型甙元:告达亭(caudatin),开德甙元(kidjolanin),萝藦甙元(Metaplexigenin)和一种新的二苯酮衍生物(Ⅳ),经光谱分析推定其结构为2,6,2′,5′-四羟基,3-乙酰基,6′-甲基二苯酮,命名白首乌二苯酮。     

Anti-trypanosomal activity of African medicinal plants: A review update

Ethnopharmacological relevance

African trypanosomiasis is one of the neglected tropical diseases caused by different species of trypanosomes that affect both human and livestock with devastating consequences in the continent. Most of the affected populations commonly use traditional medicinal plants for the treatment of the disease. Consequently, this prompted ethnopharmacological research activities on the anti-trypanosomal activity of a number of these African medicinal plants in order to validate their ethnomedicinal use. Furthermore, such studies could lead to the identification of chemical leads for the development of newer anti-trypanosomal agents from those plants. This review aims to provide updated information on the ethnopharmacological evidence of African medicinal plants with anti-trypanosomal activity.

Methods

Literature was collected via electronic search (PubMed, Sciencedirect, Medline and Google Scholar) from published articles that report on the in vitro or in vivo anti-trypanosomal activity of plants that were collected from different parts of Africa.

Results

African medicinal plants investigated for in vitro and in vivo anti-trypanosomal activity from January 1993 to October 2013 are systematically compiled and all the in vivo studies are critically discussed. A total of 264 plant species belonging to 79 families were investigated for anti-trypanosomal activity. However, only 48 bioactive anti-trypanosomal compounds were successfully isolated in pure forms. Furthermore, some of the plants were investigated for possible ameliorative effects on the trypanosome-induced pathological changes out of which 18 plants were reported to be effective while a few others were not. In spite of interesting preclinical ethnopharmacological evidence for anti-trypanosomal activity, not a single African medicinal plant was investigated in a clinical study.

Conclusion

Several African medicinal plants have demonstrated promising anti-trypanosomal effects but the studies on the anti-trypanosomal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.     

Clinical and biochemical spectrum of metabolic cardiomyopathy in Egyptian children

BackgroundInborn errors of metabolism (IEMs) commonly present with pediatric cardiomyopathy. Identification of the underlying cause is necessary as it may lead to improved outcomes.ObjectivesWe aimed to investigate the diagnostic rate, the clinical, and biochemical spectra of IEMs among Egyptian pediatric patients presenting with cardiomyopathy, and their outcome measures.MethodsWe retrospectively analyzed the clinical, biochemical, and radiological data of 1512 children diagnosed with cardiomyopathy at Cairo University Children''s Hospital over a 5-year duration.ResultsTwo hundred twenty-nine children were clinically suspected as IEMs and underwent metabolic workup. Nineteen different IEMs were confirmed in 57 (24.4%) of the suspected children. Their median age at presentation was 2.6 years and the majority had extra-cardiac manifestations. Hypertrophic cardiomyopathy represented 43/57 (75.4%) of confirmed cases, while dilated cardiomyopathy represented 13/57 (22.8%), and one patient presented with a mixed phenotype. Twenty- six patients (45.6%) survived, while 31 patients (54%) either died or were lost to follow up and assumed deceased.ConclusionsWe developed for the first time a database and a diagnostic scheme for metabolic cardiomyopathies in Egyptian children. With the recent introduction of enzyme replacement therapy, many metabolic disorders became treatable, thus establishing an early and accurate diagnosis is extremely important.     

Platinum-induced ototoxicity in pediatric cancer survivors: GSTP1 c.313A>G variant association

Hearing damage is one of the main toxic effects of platinum compounds, it derives from the irreversible degeneration of hair cells of the ear. Genetic association studies have suggested an association between GSTP1 c.313A>G variant and platinum-induced ototoxicity in childhood cancer survivors. We aimed to detect the frequency of ototoxicity and associated risk factors in survivors of childhood cancer receiving platinum-based chemotherapy and to detect the relation between GSTP1 c.313A>G (rs1695) polymorphisms and ototoxicity. We conducted a cross-sectional study on 64 cancer survivors who received platinum agents (cisplatin and/or carboplatin) at least 2 years after the end of chemotherapy. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GSTP1 c.313A>G polymorphisms. Hearing loss (HL) was identified in 16/64 patients (25%), including 62.5% treated with cisplatin and 37.5% treated with carboplatin. The greater incidence of ototoxicity was found in children treated for osteosarcoma (28.1%) followed by patients with germ cell tumors (25%) and neuroblastoma (21.9%). The AA, AG, and GG types of GSTP1 c.313A>G variant were detected in 84.4%, 9.4%, and 6.3%, respectively, of patients with HL with a significant association between mutant genotype of GSTP1 rs1695 and platinum-induced ototoxicity (P = .035). HL was not significantly associated with the total cumulative dose of cisplatin and carboplatin. GSTP1 c.313A>G variant may increase the risk of HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.     

Refined Lord–Shulman Theory for 1D Response of Skin Tissue under Ramp-Type Heat

In this article, we present a mathematical model of thermoelastic skin tissue based on a refined Lord–Shulman heat conduction theory. A small thickness of skin tissue is considered to be one-dimensional with mechanical clamped surfaces. In addition, the skin tissue’s outer surface is subjected to ramp-type heating while its inner surface is adiabatic. A simple Lord–Shulman theory, as well as the classical coupled thermoelasticity, are also applied in this article. Laplace transform techniques and their inversions are calculated to return to the time domain. Numerical outcomes are represented graphically to discuss the significant impacts on the temperature, dilatation, displacement, and stress distributions. Such results provide a more comprehensive and better insight for understanding the behavior of skin tissue during the temperature distribution of a specific boundary condition.