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INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.
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Hidrocefalia , Neuroendoscopia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/cirurgia , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Neuroendoscópios , Sistema de RegistrosRESUMO
STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.
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Criopreservação , Preservação da Fertilidade/métodos , Infertilidade Masculina/terapia , Testículo , Adolescente , Adulto , Fatores Etários , Antineoplásicos/efeitos adversos , Biópsia , Criança , Pré-Escolar , Preservação da Fertilidade/normas , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Infertilidade Masculina/etiologia , Masculino , Neoplasias/complicações , Neoplasias/terapia , Radioterapia/efeitos adversos , Contagem de Espermatozoides , Recuperação Espermática , Espermatogônias/fisiologia , Adulto JovemRESUMO
AIM: The aim of this study was to isolate and identify lipolytic bacteria. Perform a statistical stepwise physicochemical optimization for maximum production of extracellular lipase and its validation in a bioreactor. METHODS AND RESULTS: Several lipolytic bacteria were isolated from petroleum hydrocarbon-polluted soil. The strain expressing the highest lipase activity (47 U ml-1 ) was genetically identified as Gram-positive Bacillus stratosphericus PSP8 (NCBI GenBank accession no. MH120423). The response surface methodology (RSM)-central composite face centre (CCF) design of experiments was performed based on the preselected levels of the studied parameters obtained from the performed one-factor-at-a-time sequential experiments. A second-order polynomial model was predicted and improved the lipase production by approximately 1·6-fold. Preliminary scaling up of the validated optimized process was carried out in a batch 10-l stirred tank bioreactor, applying the optimum predicted operating conditions; pH 6·98, 34·8°C, 2·2 × 106 cells per ml, 200 rev min-1 , 4·82 g l-1 tributyrine concentration, 1% sucrose and 0·1% yeast extract. This yielded 89 U ml-1 at the late log phase of bacterial growth (48 h). Logistic kinetic model effectively characterized the submerged fermentation process, and the maximum specific growth and lipase production rates were estimated to be 0·338 and 0·164 h-1 respectively. CONCLUSIONS: The mesophilic and neutrophilic B. stratosphericus PSP8 isolated from petroleum hydrocarbon-contaminated soil is a proper source of lipase. The closeness of the predicted response with that of the experimental value and the enhancement of lipase productivity in fermenter scale by approximately 1·9-fold, showed that statistically optimized design can be used in order to improve the lipase production to meet the increasing demand. SIGNIFICANCE AND IMPACT OF THE STUDY: The RSM-CCF statistical optimization is useful for optimizing a large number of variables and studying their interactive effects on extracellular lipase production.
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Bacillus/enzimologia , Proteínas de Bactérias/metabolismo , Lipase/metabolismo , Bacillus/química , Bacillus/genética , Bacillus/isolamento & purificação , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Reatores Biológicos/microbiologia , Fermentação , Cinética , Lipase/química , Lipase/genética , Modelos Estatísticos , Petróleo/análise , Microbiologia do SoloRESUMO
BACKGROUND AND AIMS: Dietary pattern and lifestyle have been reported to be significant risk factors in the development of coronary heart diseases (CHD). The contribution degree of these dietary risk factors in CHD development in non-westernized countries is unclear. This study aimed to evaluate several dietary choices and their potential association with CHD. METHODS AND RESULTS: A case-control study was conducted at Prince Hamza Hospital, a referral center for coronary angiography in Amman, Jordan. Four-hundred patients referring for elective coronary angiography with clinical suspicion of coronary artery disease were enrolled. Data was collected using interview-based questionnaires. Dietary patterns were derived using Principal Component Analysis. Multivariate logistic regression was used to estimate the relationship between dietary choices and CHD. Three dietary patterns were identified. The "Healthy Dietary Pattern", which presented a diet rich in olive oil, fruits, vegetables, legumes, whole grains, fish, and low meat intake, was associated with a significant decrease in the odds of CHD (OR = 0.53, 95% CI = 0.28-0.98). The "High-Fiber Pattern", which is mainly composed of legumes and bulgur, significantly reduced the odd of CHD (OR = 0.55, 95% CI = 0.27-0.92) for the fourth quartile compared to the first one. No significant association was found between CHD and the "Western Dietary Pattern", which is loaded with refined grains, sweets and deserts, sugary drinks, and deep fried foods. CONCLUSIONS: The "Healthy Dietary Pattern" and the "High-Fiber Pattern" were associated with a decrease in odds of CHD among Jordanians.
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Doença das Coronárias/epidemiologia , Doença das Coronárias/prevenção & controle , Dieta Saudável , Dieta Ocidental/efeitos adversos , Comportamento Alimentar , Estudos de Casos e Controles , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Fibras na Dieta/administração & dosagem , Fabaceae , Feminino , Frutas , Humanos , Jordânia/epidemiologia , Masculino , Carne , Pessoa de Meia-Idade , Valor Nutritivo , Azeite de Oliva , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Alimentos Marinhos , Verduras , Grãos IntegraisRESUMO
This study aimed to assess seminal mast cells in infertile men associated with varicocele (Vx) pre- and post-surgical repair. Forty-five infertile men associated with Vx were subjected to history taking and clinical examination. In addition, semen parameters and seminal mast cells stained with 1% toluidine blue were estimated pre-varicocelectomy and three months post-varicocelectomy. Vx surgical repair revealed a significant improvement in the mean sperm concentration, progressive sperm motility, total sperm motility and sperm abnormal morphology and a significant decrement in seminal mast cells (mean ± SD, 3.56 ± 2.23 cells per high-power field (HPF) vs. 2.22 ± 1.06 cells per HPF, p = .01). The pre-operative mean mast cell count demonstrated significant increases in cases with Vx grade III compared with other Vx grades and in cases with bilateral Vx compared with unilateral Vx cases. Seminal mast cells demonstrated a significant correlation with sperm concentration, progressive sperm motility and total sperm motility and a nonsignificant correlation with age and sperm abnormal morphology. It is concluded that seminal mast cells decrease significantly in infertile men with Vx after surgical repair showing a significant negative correlation with sperm concentration, progressive sperm motility and total sperm motility.
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Mastócitos/citologia , Sêmen/citologia , Varicocele/cirurgia , Adulto , Contagem de Células , Feminino , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/imunologia , Masculino , Gravidez , Análise do Sêmen , Resultado do Tratamento , Varicocele/complicações , Procedimentos Cirúrgicos Vasculares , Adulto JovemRESUMO
Staphylococcus aureus (S. aureus) has been one of the most problematic pathogens. Methicillin Resistant S. aureus (MRSA) has emerged as a major concern for both human and animal. Antibiotic resistance genes dissemination might be possible between human and animal bacteria. The aim of this study is to show phenotypic and genotypic diversity of human and animal MRSA isolates. Antibiogram typing and biofilm production were used as a primary phenotypic typing tool for the characterization of (40) animal and (38) human MRSA isolates. Genetic typing based on sequencing of 16S rRNA gene and virulence gene profiles were done. Antimicrobial resistance profiles of the animal isolates showed little evidence of widespread of resistance, although this was seen in many human isolates. The biofilm production was detected in higher percentage among animal isolates. Based on the genetic typing and multiple antibiotic resistance (MAR) index, the majority of animal isolates clustered into lineages that were not found in human isolates. Animal and human MRSA isolates showed diversity in antibiotic resistance and virulence gene profiles may be due to host adaptation or chances for contamination between the two hosts were not present in our study.
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Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Bovinos , Análise por Conglomerados , Farmacorresistência Bacteriana/efeitos dos fármacos , Egito , Feminino , Genótipo , Humanos , Mastite Bovina/microbiologia , Mastite Bovina/patologia , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana , Fenótipo , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Infecções Estafilocócicas/patologia , Fatores de Virulência/genéticaRESUMO
In recent years, the increasing incidence of diseases caused by Staphylococcus aureus (S. aureus) has been noted in the university hospitals of El-Sharkia and Assuit governorates - Egypt. Therefore, we studied the genetic relatedness of multidrug resistant S. aureus isolates from different sources in the above mentioned governorates. One hundred and fifty six S. aureus isolates were divided into 5 different groups, 1 non clinical isolates from different food products and 4 different clinical isolates of human and animal sources in the 2 different governorates. Epidemiological characteristics of 156 S. aureus isolates were determined by phenotypic methods including quantitative antibiogram typing and biofilm production. Genetic typing of 35 multidrug resistant (MDR) isolates (7 from each group) based on 16S rRNA gene sequence, virulence and antimicrobial resistance gene profiles was done. The genetic relatedness of the highest virulent strain from each group was detected based on different single locus sequence typing and multi-locus sequence typing (MLST). S. aureus strains isolated from different sources and geographical areas showed high diversity. The genetic typing revealed different sequence types and different sequences of coa and spa genes. S. aureus isolates were found highly diverse in Egypt.
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Farmacorresistência Bacteriana Múltipla/genética , Variação Genética , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Animais , Sequência de Bases , Egito , Perfilação da Expressão Gênica , Genes Bacterianos , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Staphylococcus aureus/patogenicidade , Virulência/genéticaRESUMO
Waterpipe tobacco smoking is increasing in popularity, particularly among young adults. This popularity is related to the lack knowledge regarding the health effects of waterpipe smoking. In this study, we examined the genotoxicity of waterpipe smoking using an 8-hydroxy deoxyguanosine (8-OHdG) assay. Genotoxicity was evaluated in the saliva, urine, and serum of 66 waterpipe adult smokers and 46 healthy nonsmokers. The level of addiction to waterpipe smoking was evaluated using the Lebanon Waterpipe Dependence Scale-11. Levels of 8-OHdG in the samples were measured using commercially available enzyme-linked immunosorbent assays. Levels of 8-OHdG in the saliva (52,430 ± 2923 vs 48,430 ± 4189 pg/mL), urine (2815 ± 312 vs 2608 ± 180 pg/mL), and serum (19,720 ± 202 vs 19,670 ± 254 pg/mL) were similar between waterpipe smokers and nonsmokers (P > 0.05). In addition, no correlations were found between dependence score and levels of 8-OHdG in all sample types. In conclusion, 8-OHdG is not a good biomarker for genotoxic effect of waterpipe smoking.
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Desoxiguanosina/análogos & derivados , Mutagênicos/toxicidade , Nicotiana/química , Nicotiana/toxicidade , Fumar/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Criança , Estudos Transversais , Desoxiguanosina/sangue , Desoxiguanosina/metabolismo , Desoxiguanosina/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Adulto JovemRESUMO
Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.
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Artrite Experimental/tratamento farmacológico , Aspirina/farmacologia , Ácidos Linoleicos/farmacologia , Óleos de Plantas/farmacologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Ácido gama-Linolênico/farmacologia , Administração Oral , Angiopoietina-1/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Aspirina/administração & dosagem , Celecoxib , Progressão da Doença , Quimioterapia Combinada , Inflamação/tratamento farmacológico , Inflamação/patologia , Ácidos Linoleicos/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Oenothera biennis , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Pirazóis/administração & dosagem , Ratos , Ratos Wistar , Sulfonamidas/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Ácido gama-Linolênico/administração & dosagemRESUMO
SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. This novel compound is an oligonucleotide consisting of decitabine linked through a phosphodiester bond to the endogenous nucleoside deoxyguanosine. The dinucleotide configuration provides protection from drug clearance by deamination, while maintaining at least equivalent effects on gene-specific and global hypomethylation both in vitro and in animal model systems. This agent is currently being tested in phase I and II clinical trials in humans and has been demonstrated to be safe and well tolerated as a single agent, with evidence of promising activity in heavily pretreated (including currently FDA approved hypomethylating drugs) myelodysplastic syndrome and acute myeloid leukemia patients. Ongoing trials are also open in platinum-resistant ovarian cancer and hepatocellular carcinoma.
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To evaluate the organochlorine pesticide (OCP) contamination of Manzala Lake, its ecosystem was investigated during the winter season (December to March). The studied ecosystem components were water, sediment, aquatic weeds, and fishes in four locations. The samples were analyzed by gas chromatography with electron capture detector. Pollutant levels of total OCPs showed significantly high levels in the water areas of Round road (46.253 ng/ml), Port-Said Damietta road (19.301 ng/ml), followed by Bughas El-Rasoah (5.539 ng/ml), then Ashtoum El Gamel (natural reserve area now) (0.289 ng/ml). Organochlorines were detected in sediment only in Round road (3.359 µg/kg) and Port-Said Damietta road (0.171 µg/kg) by significant order while they were undetectable in Ashtoum El Gamel and Bughas El-Rasoah. Total OCPs in aquatic weeds ranged between 0.194 µg/kg in Port-Said Damietta and 0.026 µg/kg in Ashtoum El Gamel. While OCPs were 0.160 and 0.153 µg/kg in Round road and Bughas El-Rasoah, respectively. Concerning fish muscles OCPs were significantly higher in the Round road area (0.397 µg/kg) followed by the Port-Said Damietta road (0.258 µg/kg), and finally, Ashtoum El Gamel samples (0.126 µg/kg). The results revealed the direct relation for the accumulation of OCPs between studied ecosystem parameters at the Manzala Lake during the winter season. Results also demonstrated that fish samples collected from the Manzala Lake in the studied areas were contaminated with levels of organochlorines, not higher than the maximum permissible level recorded by FAO/WHO, and that the public is not at risk with fish consumption.
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Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Lagos/química , Resíduos de Praguicidas/análise , Poluentes Químicos da Água/análise , Animais , Ecossistema , Peixes/metabolismo , Sedimentos Geológicos/química , Hidrocarbonetos Clorados/metabolismo , Resíduos de Praguicidas/metabolismo , Estações do Ano , Poluentes Químicos da Água/metabolismo , Poluição Química da Água/estatística & dados numéricosRESUMO
This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
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Acetaminofen , Dor Aguda , Adulto , Humanos , Acetaminofen/uso terapêutico , Ibuprofeno/uso terapêutico , Oxicodona/uso terapêutico , Metanálise em Rede , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Analgésicos Opioides/uso terapêutico , Extração Dentária/efeitos adversos , Dor Aguda/tratamento farmacológico , Dor Aguda/etiologiaRESUMO
The omega-3 fatty acid eicosapentaenoic acid (EPA) is a superb nature's medicine, with still unfolding health benefits. Because hepatotoxicity is a prominent adverse drug reaction, we currently attempted a new approach in which EPA was challenged to both alleviate hepatotoxicity and provide synergy with anticonvulsant effects of valproate (VPA). Besides, we verified whether EPA may kinetically modulate the clearance rate of VPA. VPA (500mg/kg p.o., for 2weeks) caused rat hepatotoxicity that was manifested as notable (2- to 4-fold) rise in serum liver enzymes (GGT, ALT, and ALP), increased hepatic levels of lipid peroxides and TNF-α (3- and 7-fold) and activity of myeloperoxidase (MPO, 4-fold), lowering of serum albumin (42%), and depletion of liver reduced glutathione (GSH, 36%). Furthermore, histopathologic examination revealed hepatocellular degeneration, focal pericentral necrosis, infiltration of inflammatory cells, and steatosis. Joint treatment with EPA (300mg/kg) blunted the oxidative stress, TNF-α levels and MPO activity, while enhanced levels of serum albumin and hepatic GSH. EPA also ameliorated most of the hepatocellular anomalies evoked by VPA. Additionally, in a mouse PTZ convulsion model, EPA markedly augmented the anticonvulsant effects of VPA far beyond their single responses. On the other hand, pharmacokinetic analyses revealed that joint EPA administration had no effect on serum VPA concentrations. Collectively, results demonstrate for the first time that the ω-3 FA (EPA) markedly alleviated VPA-induced hepatotoxicity, oxidative stress, and inflammation, while enhanced its anticonvulsant effects without altering its clearance. Therapeutically, these protective and synergy profiles for EPA foster a more safe and efficacious drug combination regimen than VPA.
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Ácido Eicosapentaenoico/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ácido Valproico/farmacocinética , Ácido Valproico/toxicidade , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/toxicidade , Interações Medicamentosas , Ácido Eicosapentaenoico/administração & dosagem , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Ácido Valproico/administração & dosagem , gama-Glutamiltransferase/sangueRESUMO
Viral hepatitis is a major problem in Egypt. To define the epidemiology of the disease, sentinel surveillance was established in 5 hospitals in diverse areas of the country in 2001. Data were completed for patients meeting the case definition for viral hepatitis. Of a total of 5909 patients evaluated, 4189 (70.9%) showed positive antibody markers for hepatitis. Out of those, 40.2% had evidence of hepatitis A virus (HAV) infection, 30.0% hepatitis B virus (HBV) and 29.8% hepatitis C virus (HCV) infection. This surveillance system was useful in identifying the variable endemicity of acute HAV infection in different regions and for better understanding the epidemiology of HBV and HCV infection.
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Hepatite A/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Vigilância de Evento Sentinela , Doença Aguda , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Egito/epidemiologia , Doenças Endêmicas/estatística & dados numéricos , Feminino , Hepatite A/diagnóstico , Hepatite A/transmissão , Hepatite B/diagnóstico , Hepatite B/transmissão , Hepatite C/diagnóstico , Hepatite C/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência , Fatores de Risco , Estações do Ano , Estudos Soroepidemiológicos , Distribuição por SexoRESUMO
PURPOSE: Tomudex (ZD1694; Zeneca Ltd, Macclesfield, United Kingdom) appears to have a favorable toxicity profile (defined in phase I studies) and antitumor activity in a broad range of epithelial tumors. We report here the results of a large phase II study of Tomudex in advanced colorectal cancer (CRC). PATIENTS AND METHODS: One hundred seventy-seven patients were entered onto the study between October 1992 and September 1993. Patients were required to have advanced CRC without prior chemotherapy (adjuvant chemotherapy was permissible) and at least one measurable lesion. Tomudex (ZD1694) was administered at a dose of 3 mg/m2 intravenously once every 3 weeks in the absence of toxicity or disease progression. Patients were assessed for objective response, progression, and survival. RESULTS: Of 177 patients entered onto the study, 5% had received prior adjuvant chemotherapy and 83% had liver metastases. Objective responses were seen in 26% of patients (95% confidence interval, 19% to 33%; four complete responses [CRs] and 41 partial responses [PRs]) while median time to progression was 4.2 months and median survival 9.6 months. All sites were audited, and responses were reviewed by an independent panel. Common toxicities included mild reversible transaminitis, nausea and vomiting, and asthenia or flu-like symptoms, and World Health Organization (WHO) grade 3 and 4 leukopenia and diarrhea were seen in 6% and 9.8% of patients, respectively. Stomatitis and alopecia were common. CONCLUSION: In this large multicenter phase II study of patients with advanced CRC, interesting activity was seen (objective response rate, 26%). In addition, Tomudex has an acceptable toxicity profile and a convenient dosing schedule (single intravenous injection every 3 weeks) and thus appears to offer real potential as a novel agent for the treatment of patients with advanced CRC.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quinazolinas/uso terapêutico , Tiofenos/uso terapêutico , Timidilato Sintase/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/efeitos adversos , Indução de Remissão , Análise de Sobrevida , Tiofenos/efeitos adversosRESUMO
PURPOSE: To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment. PATIENTS AND METHODS: Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of results from each trial. RESULTS: The median follow-up duration was approximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [CI], 0.75 to 1.24) for anastrozole 1 mg versus megestrol acetate and 0.92 (97.5% CI, 0.71 to 1.19) for anastrozole 10 mg versus megestrol acetate. The overall median time to progression was approximately 21 weeks. Approximately one third of patients in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partial response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respectively, had stable disease for > or = 24 weeks. For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the difference between the anastrozole 10 mg and megestrol acetate groups was significant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group. More than 30% of megestrol acetate-treated patients had weight gain > or = 5%, and 10% of patients had weight gain > or = 10%. Patients who received megestrol acetate continued to gain weight over time. CONCLUSION: Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment.
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Antineoplásicos/uso terapêutico , Inibidores da Aromatase , Neoplasias da Mama/tratamento farmacológico , Megestrol/análogos & derivados , Nitrilas/uso terapêutico , Pós-Menopausa , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Antineoplásicos/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Megestrol/efeitos adversos , Megestrol/uso terapêutico , Acetato de Megestrol , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Prognóstico , Taxa de Sobrevida , Tamoxifeno/uso terapêutico , Triazóis/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: We sought to compare the accuracy of a volumetric fully automated computer assessment of hippocampal volume asymmetry versus neuroradiologists' interpretations of the temporal lobes for mesial temporal sclerosis. Detecting mesial temporal sclerosis (MTS) is important for the evaluation of patients with temporal lobe epilepsy as it often guides surgical intervention. One feature of MTS is hippocampal volume loss. MATERIALS AND METHODS: Electronic medical record and researcher reports of scans of patients with proved mesial temporal sclerosis were compared with volumetric assessment with an FDA-approved software package, NeuroQuant, for detection of mesial temporal sclerosis in 63 patients. The degree of volumetric asymmetry was analyzed to determine the neuroradiologists' threshold for detecting right-left asymmetry in temporal lobe volumes. RESULTS: Thirty-six patients had left-lateralized MTS, 25 had right-lateralized MTS, and 2 had bilateral MTS. The estimated accuracy of the neuroradiologist was 72.6% with a κ statistic of 0.512 (95% CI, 0.315-0.710) [moderate agreement, P < 3 × 10(-6)]), whereas the estimated accuracy of NeuroQuant was 79.4% with a κ statistic of 0.588 (95% CI, 0.388-0.787) [moderate agreement, P < 2 × 10(-6)]). This discrepancy in accuracy was not statistically significant. When at least a 5%-10% volume discrepancy between temporal lobes was present, the neuroradiologists detected it 75%-80% of the time. CONCLUSIONS: As a stand-alone fully automated software program that can process temporal lobe volume in 5-10 minutes, NeuroQuant compares favorably with trained neuroradiologists in predicting the side of mesial temporal sclerosis. Neuroradiologists can often detect even small temporal lobe volumetric changes visually.
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Epilepsia do Lobo Temporal/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Lobo Temporal/patologia , Adulto , Epilepsia do Lobo Temporal/patologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos , Esclerose/patologia , SoftwareRESUMO
Elliptinium acetate (Celiptium) is an intercalating agent belonging to the ellipticine family. This agent has demonstrated clinical activity as salvage treatment in breast cancer using a weekly regimen. However, its clinical use was hampered by important toxicities such as xerostomia and immune-mediated haemolytic reactions due to development of anti-elliptinium IgM antibodies. We have studied 83 patients previously treated for metastatic breast cancer using elliptinium acetate with a different schedule: 80 mg/m2 daily for 3 consecutive days every 21 days. In 80 evaluable patients, an objective response (complete + partial response) was obtained in 5 of 30 patients with visceral metastases (13%), in 6 of 21 patients with soft tissue metastases (29%), and in 3 of 20 patients with mixed metastases (15%). The overall objective response rate was 14/80 (18%, 95% confidence interval = 10-26%). Moderate to severe xerostomia occurred in 10% of patients, while no anti-elliptinium antibodies or haemolytic reactions were detected using this schedule. No significant haematological toxicity, as usually reported with this drug, was observed. Elliptinium acetate has modest but definite activity as salvage treatment of breast cancer. The 3-week schedule seems as active as and less toxic than the weekly schedule.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Elipticinas/uso terapêutico , Substâncias Intercalantes/uso terapêutico , Adulto , Idoso , Elipticinas/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Salvação , Xerostomia/induzido quimicamenteRESUMO
We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.
Assuntos
Febre/tratamento farmacológico , Rim/efeitos dos fármacos , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Pefloxacina/uso terapêutico , Piperacilina/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Combinada/uso terapêutico , Feminino , Febre/etiologia , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neutropenia/etiologia , Pefloxacina/efeitos adversos , Piperacilina/efeitos adversos , Vancomicina/uso terapêuticoRESUMO
ZD1694 (Tomudex) is a new antifolate which is a specific inhibitor of thymidylate synthase (TS). Evidence suggests that ZD1694 has a spectrum of activity that only partially overlaps with 5-fluorouracil (modulated with leucovorin) against colon tumours in vitro. Potent cytotoxic activity is dependent upon active uptake into cells via the reduced folate/methotrexate cell membrane carrier (RFC) and subsequent metabolism to polyglutamated forms (tri, tetra and pentaglutamates). These polyglutamates are approximately 60-fold more active as TS inhibitors and are not effluxed readily from cells. Extensive polyglutamation also occurs in various mouse tissues (e.g. small intestinal epithelium, liver and kidney), resulting in high tissue/plasma drug ratios which persist for a prolonged period. ZD1694 has antitumour activity in mice, although the high plasma thymidine in this species complicates: (1) the interpretation of therapeutic index; (2) tumour types in which activity is likely to be observed; and (3) translation of doses and schedules for clinical evaluation. ZD1694 entered clinical study and has completed Phase I and II evaluation, with activity observed in several tumour types. Appreciable activity in the Phase II colorectal study (29% objective response rate on interim analysis) led to the current Phase III study, randomised against 5-fluorouracil/leucovorin.