RESUMEN
Nutrient enrichment disrupts plant-animal interactions and ecosystem functioning globally. In woodland systems, the mechanisms of bottom-up turnover on plant-herbivore interactions remain understudied. Here, we performed a full-factorial field experiment to evaluate the interactive effects of nutrient addition (nitrogen, phosphorus, and/or potassium) on the assemblage of foliar herbivores and the interaction frequency with Berberis microphylla, a dominant shrub species in Patagonian woodlands. Additionally, we assessed whether these effects could be mediated by changes in vegetative traits and microhabitat characteristics (i.e., canopy cover) that may ultimately influence the foraging behavior of herbivores. The addition of nitrogen reduced the herbivory frequency by 41%, yet this effect was diluted in the presence of potassium. We found no effects of phosphorus addition. Our results suggest that the impact of multiple nutrient additions (N and K) on herbivory patterns could be mediated by changes in two important foliar traits, leaf size and leaf density. This study shows how multiple nutrient addition can change the magnitude of antagonistic plant-animal interactions in woodlands. Since herbivory by arthropods has a relevant role in net primary productivity, our results highlight the importance of buffering human-driven woodland eutrophication to maintain important ecological functions (e.g., herbivory) associated with antagonistic plant-animal interactions and avoiding ecosystem dysfunction.
Asunto(s)
Ecosistema , Herbivoria , Animales , Eutrofización , Bosques , Humanos , NutrientesRESUMEN
BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/patología , Floxuridina/administración & dosificación , Hepatectomía , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/prevención & control , Adulto , Quimioterapia Adyuvante/instrumentación , Quimioterapia Adyuvante/métodos , Ensayos Clínicos Fase III como Asunto , Neoplasias Colorrectales/mortalidad , Humanos , Bombas de Infusión Implantables , Infusiones Intraarteriales/instrumentación , Infusiones Intraarteriales/métodos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Estudios Multicéntricos como Asunto , Países Bajos , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Adulto JovenRESUMEN
The oral multikinase inhibitor sorafenib undergoes extensive UGT1A9-mediated formation of sorafenib-ß-D-glucuronide (SG). Using transporter-deficient mouse models, it was previously established that SG can be extruded into bile by ABCC2 or follow a liver-to-blood shuttling loop via ABCC3-mediated efflux into the systemic circulation, and subsequent uptake in neighboring hepatocytes by OATP1B-type transporters. Here we evaluated the possibility that this unusual process, called hepatocyte hopping, is also operational in humans and can be modulated through pharmacological inhibition. We found that SG transport by OATP1B1 or murine Oatp1b2 was effectively inhibited by rifampin, and that this agent can significantly increase plasma levels of SG in wildtype mice, but not in Oatp1b2-deficient animals. In human subjects receiving sorafenib, rifampin acutely increased the systemic exposure to SG. Our study emphasizes the need to consider hepatic handling of xenobiotic glucuronides in the design of drug-drug interaction studies of agents that undergo extensive phase II conjugation.
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Glucurónidos/farmacología , Glucurónidos/farmacocinética , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/farmacocinética , Anciano , Animales , Transporte Biológico/efectos de los fármacos , Perros , Femenino , Glucurónidos/administración & dosificación , Células HEK293 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Células de Riñón Canino Madin Darby , Masculino , Ratones Noqueados , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Niacinamida/administración & dosificación , Niacinamida/farmacocinética , Niacinamida/farmacología , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Compuestos de Fenilurea/administración & dosificación , Rifampin/farmacología , SorafenibRESUMEN
The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥ 30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥ 30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.
Asunto(s)
Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Adulto , Cuello del Útero/patología , Cuello del Útero/virología , Femenino , Humanos , Persona de Mediana Edad , Sondas de Oligonucleótidos , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Estándares de Referencia , Sensibilidad y Especificidad , Adulto Joven , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. METHODS: Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m(-2) with 75 mg m(-2) docetaxel, then from 30 to 35 mg m(-2) with 100 mg m(-2) docetaxel. Recommended phase II dose cohorts were expanded. RESULTS: Fifty-eight patients were treated. Recommended phase II doses were 35 mg m(-2) ombrabulin with 75 mg m(-2) docetaxel (35/75 mg m(-2); 13 patients) and 30 mg m(-2) ombrabulin with 100 mg m(-2) docetaxel (30/100 mg m(-2); 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m(-2) docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m(-2) ombrabulin), eight lasting >3 months. CONCLUSIONS: Sequential administration of ombrabulin with 75 or 100 mg m(-2) docetaxel every 3 weeks is feasible.
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Inhibidores de la Angiogénesis/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias/tratamiento farmacológico , Serina/análogos & derivados , Taxoides/farmacocinética , Adolescente , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Docetaxel , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Serina/administración & dosificación , Serina/efectos adversos , Serina/farmacocinética , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
The organic cation transporter 2 (OCT2) regulates uptake of cisplatin in proximal tubules, and inhibition of OCT2 protects against severe cisplatin-induced nephrotoxicity. However, it remains uncertain whether potent OCT2 inhibitors, such as cimetidine, can influence the antitumor properties and/or disposition of cisplatin. Using an array of preclinical assays, we found that cimetidine had no effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with high OCT2 mRNA levels (IGROV-1 cells). Moreover, the antitumor efficacy of cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100 mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg × 2) revealed that cimetidine did not alter exposure to unbound cisplatin, a marker of antitumor efficacy (4.37 vs. 4.38 µg·h/ml; P = 0.86). These results support the future clinical exploration of OCT2 inhibitors as specific modifiers of cisplatin-induced nephrotoxicity.
Asunto(s)
Antineoplásicos/uso terapéutico , Cimetidina/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Cimetidina/administración & dosificación , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Sinergismo Farmacológico , Femenino , Células HEK293 , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Masculino , Ratones , Persona de Mediana Edad , Proteínas de Transporte de Catión Orgánico/metabolismo , Transportador 2 de Cátion Orgánico , Neoplasias Ováricas/metabolismoRESUMEN
BACKGROUND: High-risk (hr)HPV testing plays an important role in primary cervical cancer screening. Subsequent hrHPV genotyping might contribute to better risk stratification. The majority of hrHPV tests do not include identification of individual hrHPV genotypes. OBJECTIVES: The digene HPV Genotyping RH Test (strip-based) and LQ Test (xMAP-based) allow genotyping of GP5+/6+ amplimers, but their probes target a region in the L1 ORF, which is also amplified by other broad-spectrum hrHPV assays, e.g., the Roche Amplicor HPV Test (Amplicor) and the Roche Linear Array. The goal was to test whether the RH Test and LQ Test can be used as an universal hrHPV genotyping test. STUDY DESIGN: Self-collected cervico-vaginal specimens (n=416) from an epidemiologic study were analyzed with Amplicor. The amplimers obtained were also tested with the RH Test and LQ Test for identification of 18 HPV types, including the 13 hrHPVs targeted by Amplicor. RESULTS: 197 specimens were positive by Amplicor, in which the RH Test and LQ Test identified one of the 13 hrHPVs in 94.4% and 98.0%, respectively. In 219 specimens remaining negative by Amplicor, the RH Test and LQ Test, performed on the Amplicor amplification products, still detected one of the 13 hrHPVs in 3.7% and 5.5%, respectively, and include identification of HPV53, 66, and 82. Overall, the RH and LQ Tests demonstrated high concordance with Amplicor for hrHPV detection (κ=0.908 and κ=0.923, respectively). CONCLUSIONS: The digene HPV Genotyping RH and LQ Tests can be directly used for amplimers generated by the Amplicor HPV Test.
Asunto(s)
ADN Viral/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Juego de Reactivos para Diagnóstico , Adolescente , Adulto , Técnicas de Laboratorio Clínico , Detección Precoz del Cáncer/métodos , Femenino , Genotipo , Humanos , Tamizaje Masivo/métodos , Reacción en Cadena de la Polimerasa , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Adulto JovenRESUMEN
Chlamydia trachomatis (Ct) comprises 3 serogroups and 19 serovars. Different genotyping methods are available to differentiate between the serovars. The aim of this study was to evaluate the sensitivity and discriminatory power of three genotyping methods, respectively Omp1 sequencing, the Ct Detection and genoTyping (DT) assay and the pmpH real-time PCR discriminating an LGV infection from a non-LGV infection. In total, 50 Aptima Combo 2 (AC2) Ct positive samples were selected and tested with the 3 genotyping methods. The Ct-DT assay detected 3 double Ct infections that caused a non interpretable result by Omp1 sequencing, while Omp1 sequencing has a higher discriminatory power that gave additional information about Ct genovariants. All three methods detected the 6 LGV samples. Although the pmpH real-time PCR detected all LGV infections, a substantial amount (24%) of non-LGV infections were missed. The sensitivity compared to AC2 Ct detection was 80% (95% CI 67-89%) for the Ct-DT assay, 72% (95% CI 58-83%) for Omp1 sequencing and 64% (95% CI 50-76%) for the pmpH real-time PCR. In conclusion, the Ct-DT assay is appropriate for serovar distribution studies, epidemiological studies and differentiation between an LGV and non-LGV Ct infection, while Omp1 sequencing is more appropriate for phylogenetic studies. The pmpH real-time PCR is suitable as second assay to differentiate between an LGV and non-LGV infection, but not as primary detection assay, due to its low sensitivity for non-LGV strains.
Asunto(s)
Proteínas Bacterianas/genética , Chlamydia trachomatis/genética , Linfogranuloma Venéreo/diagnóstico , Tipificación Molecular/métodos , Proteínas de la Membrana Bacteriana Externa/genética , Chlamydia trachomatis/clasificación , Sondas de ADN , ADN Bacteriano/química , ADN Bacteriano/genética , Femenino , Genotipo , Humanos , Linfogranuloma Venéreo/microbiología , Masculino , Hibridación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa/métodos , Porinas/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Squamous cell carcinoma of the conjunctiva (SCCC) is associated with HIV-related immunosuppression, but human papillomavirus virus (HPV) is also suspected to have a role. We carried out a case-control study to assess the role of cutaneous and mucosal HPV types in SCCC, conjunctival dysplasia, and their combination (SCCC/dysplasia) in Uganda. METHODS: We compared HPV prevalence in frozen biopsies from 94 SCCC cases (79 of whom were found to be HIV-positive), 39 dysplasia cases (34 HIV-positive), and 285 hospital controls (128 HIV-positive) having other eye conditions that required surgery. Highly sensitive PCR assays that detect 75 HPV types were used. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed, adjusting for, or stratifying by age, sex, and HIV status. RESULTS: Cutaneous HPV types were detected in 45% of SCCC cases, 41% of dysplasia cases and 11% of controls. Human papillomavirus virus 5 and 8 were the most common types in SCCC, and most often occurred in combination with other types. Associations were observed between SCCC/dysplasia and detection of both single (OR=2.3; 1.2-4.4) and multiple (OR=18.3; 6.2-54.4) cutaneous HPV types, and were chiefly based on findings in HIV-positive patients. Cutaneous HPV infections were rarely observed among HIV-negative patients and the association with SCCC/dysplasia was not significant (OR=2.4; 0.6-9.6) among them. Squamous cell carcinoma of the conjunctiva/dysplasia risk and mucosal HPV types were not associated in either HIV-positive or HIV-negative patients. CONCLUSIONS: We detected cutaneous HPV types in nearly half of SCCC/dysplasia cases and often multiple types (HPV5 and 8 being most common). The role of HIV (confounder or strong enhancer of cutaneous HPV carcinogenicity) is still uncertain.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Carcinoma de Células Escamosas/virología , Neoplasias de la Conjuntiva/virología , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedades de la Conjuntiva/patología , Enfermedades de la Conjuntiva/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Full healing was achieved following the circumferential application of VAC therapy to prepare a large lower-extremity wound involving both soft-tissue injury and femoral fractures for grafting. No complications were reported.
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Traumatismos de la Pierna/terapia , Terapia de Presión Negativa para Heridas/métodos , Cuidados de la Piel/métodos , Traumatismos de los Tejidos Blandos/terapia , Accidentes de Tránsito , Adulto , Fracturas del Fémur/complicaciones , Fracturas del Fémur/cirugía , Humanos , Traumatismos de la Pierna/etiología , Traumatismos de la Pierna/patología , Masculino , Necrosis , Cuidados Posoperatorios/métodos , Trasplante de Piel/métodos , Traumatismos de los Tejidos Blandos/etiología , Traumatismos de los Tejidos Blandos/patología , Supuración , Cicatrización de HeridasRESUMEN
Resistance of cancer cells to cytotoxic therapy can be caused by the activation of strong anti-apoptotic effectors, for example NF-kappaB. Therefore, compounds that inhibit NF-kappaB stimulation might overcome chemotherapy resistance. F60008, a semi-synthetic derivate of triptolide, is converted to triptolide in vivo and activates apoptosis in human tumour cells. We performed a phase I and pharmacological study of F60008 given intravenously as a weekly infusion for 2 weeks every 3 weeks in patients with advanced solid tumours. Twenty patients were enrolled, and a total of 35 cycles were administered. The most frequent haematological side-effect was mild grade 1-2 anaemia. Non-haematological toxicities included fatigue, nausea, vomiting, diarrhoea and constipation, all grade 1-2. Two lethal events were observed in which an increase in caspase-3 activity and overt apoptosis in monocytes and neutrophils could be seen. Pharmacokinetic studies showed high inter-individual variability and rendered F60008 a far from optimal derivate of triptolide.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Apoptosis/efectos de los fármacos , Diterpenos/administración & dosificación , Neoplasias/tratamiento farmacológico , Fenantrenos/administración & dosificación , Adulto , Anciano , Anemia/inducido químicamente , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/sangre , Diterpenos/efectos adversos , Diterpenos/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Leucocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Fenantrenos/efectos adversos , Fenantrenos/sangreRESUMEN
BACKGROUND: Based on epidemiologic studies, 18 mucosal human papillomavirus (HPV) types have been classified as (probably) high-risk (HR) (i.e., HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82). Recognition of HR HPV at the individual type level may be valuable in clinical management of HR HPV-positive women. OBJECTIVES: The goal of this study was to evaluate the performance of the novel digene HPV Genotyping RH Test (digene RH Test), which uses type-specific probes for the 18 HR HPV genotypes, in comparison to the established in-house Reverse Line Blot (RLB) genotyping assay on PCR products generated with the clinically validated GP5+/6+-PCR method. STUDY DESIGN: GP5+/6+ amplimers, generated from 493 digene High Risk HPV HC2 DNA Test (HC2)-positive and 95 HC2-negative cervical smears, were genotyped by both the digene RH Test and the RLB assay. RESULTS: Both genotyping assays demonstrated high concordance for overall HR HPV detection (ú = 0.886) and type-specific identification of the 18 HR types (overall ú = 0.951, individual ú range 0.777 to 1.000) in 493 HC2-positive samples. The digene RH Test revealed positivity for one or more HR HPV type(s) in 86.6% of the HC2-positive women, and negativity was confirmed in 97.9% of the HC2-negative women. CONCLUSIONS: The digene HPV Genotyping RH Test revealed a high genotyping agreement with the established RLB assay on GP5+/6+ amplimers. Accordingly, this assay following GP5+/6+-PCR could serve as a follow-up test in a clinical setting for women who are HC2-positive to identify the respective HR HPV genotype(s).
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus/diagnóstico , Juego de Reactivos para Diagnóstico , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico , Sondas de ADN , ADN Viral/análisis , ADN Viral/genética , Femenino , Genes Virales , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Especificidad de la Especie , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/etiologíaRESUMEN
BACKGROUND: Epidemiologic studies have classified 18 genotypes of the human papillomavirus (HPV) as (probably) high-risk (HR) based on their association with cervical cancer, i.e., HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82. Given the fact that certain HR HPV types confer an increased risk of cervical (pre)cancer, type-specific identification might aid clinical management of women tested positive for HR HPV. Therefore, the development of robust, high-throughput genotyping assays is important. OBJECTIVES: An analytical comparison of the digene HPV Genotyping LQ Test (digene LQ Test), capable of identifying 18 HR types using bead-based xMAP suspension array technology, with the established Reverse Line Blot (RLB) genotyping assay was carried out on amplimers generated with the clinically validated GP5+/6+-PCR method. STUDY DESIGN: GP5+/6+ amplimers, generated from 434 digene High Risk HPV HC2 DNA Test (HC2)-positive and 95 HC2-negative cervical smears, were genotyped by both the digene LQ Test and the RLB genotyping assay. RESULTS: The genotyping assays revealed high agreement for overall HR HPV detection (ú = 0.884) and type-specific identification of the 18 HR HPV types (overall ú = 0.958, individual ú range 0.795 to 1.000). The digene LQ Test demonstrated a very good inter-laboratory reproducibility (ú = 0.987). Among the HC2-positive women, the digene LQ Test revealed positivity for one or more HR HPV type(s) in 85.9%, and negativity was observed in 97.9% of the HC2-negative women. CONCLUSIONS: The digene LQ Test demonstrated a high genotyping agreement with the established RLB genotyping assay on GP5+/6+ amplimers. This novel assay allows for high-throughput genotyping following HR HPV testing by HC2.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus/diagnóstico , Juego de Reactivos para Diagnóstico , Alphapapillomavirus/genética , Alphapapillomavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico , ADN Viral/análisis , ADN Viral/genética , Femenino , Genes Virales , Humanos , Tamizaje Masivo/métodos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Riesgo , Sensibilidad y Especificidad , Especificidad de la Especie , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/etiologíaRESUMEN
Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.
Asunto(s)
Conductos Biliares Extrahepáticos , Neoplasias del Sistema Biliar/microbiología , Neoplasias de la Vesícula Biliar/microbiología , Helicobacter/aislamiento & purificación , Femenino , Humanos , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Maggot debridement therapy is generally a safe therapy that is typically used as a last resort treatment for debriding wounds in patients with multiple comorbidities. We describe a case of serious bleeding in an 87-year-old woman treated in our wound care center for a mixed arterial-venous ulcer of the right leg. Daily home visits were completed by a wound care nurse, resulting in prompt recognition and management of the bleeding. The patient was transported to hospital via an ambulance, and rapidly stabilized with intravenous fluids and a blood transfusion. She subsequently returned to the home care setting for additional management of her lower extremity wound.
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Desbridamiento/métodos , Desbridamiento/enfermería , Hemorragia/etiología , Larva , Anciano de 80 o más Años , Animales , Desbridamiento/efectos adversos , Femenino , Hemorragia/prevención & control , Humanos , Resultado del TratamientoRESUMEN
This retrospective study found that use of autologous platelet-rich fibrin on a range of hard-to-heal wounds achieved full healing or a significant reduction in wound diameter with no adverse effects. Prospective studies are now needed
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Plaquetas , Adhesivo de Tejido de Fibrina/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pierna , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy. MATERIALS AND METHODS: Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collected from patients operated upon for PPU. By means of PCR, DEIA, and LIPA the presence of the "cytotoxin associated gene" (cagA) and the genotype of the "vacuolating cytotoxin gene" were determined. RESULTS: Fluid from the nasogastric tube was obtained from 25 patients, lavage fluid from 26 patients, serum samples from 20 patients and biopsies from 18 patients. Several genotypes were found, of which the vacA s1 cagA positive strains were predominant. Additionally, a correlation was found between the H. pylori presence in biopsy and its presence in lavage fluid (p=0.015), rendering the latter as an alternative for biopsy. Sensitivity and specificity of lavage fluid analysis were 100% and 67%, respectively. CONCLUSION: This study shows the vacA s1 cagA positive strain is predominant in a PPU population. The correlation found between the H. pylori presence in biopsy and its presence in lavage fluid suggests that analysis of the lavage fluid is sufficient to determine the H. pylori presence. Risks associated with biopsy taking may be avoided.
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Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Úlcera Péptica Perforada/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Bacterianos/aislamiento & purificación , Proteínas Bacterianas/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/microbiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eight patients were enrolled. Dose levels were 10, 20, 30, 45, 70, 85, and 100 mg. At 100 mg dose-limiting toxicity (DLT) (common toxicity criteria grade 3 skin rash and grade 3 diarrhoea despite treatment with loperamide) occurred in two patients. In the next-lower dose of 70 mg, DLT (grade 3 fatigue and ALAT elevation) occurred in one of six patients. An intermediate dose level of 85 mg was studied. Here DLT occurred in two patients (grade 3 diarrhoea despite treatment and grade 2 diarrhoea lasting more than 7 days despite treatment). An additional 12 patients were treated at 70 mg. BIBW 2992 PK after single and multiple doses revealed moderately fast absorption, and no deviation from dose proportionality. Pharmacodynamics analysis in skin biopsies did not show significant changes in EGFR-associated biomarkers. However, a significant inhibitory effect on the proliferation index of epidermal keratinocytes was observed. No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD.
Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Quinazolinas/administración & dosificación , Receptor ErbB-2/antagonistas & inhibidores , Adolescente , Adulto , Afatinib , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Quinazolinas/efectos adversos , Quinazolinas/farmacocinética , Piel/citología , Piel/efectos de los fármacos , Piel/metabolismo , Factores de Tiempo , Distribución Tisular , Resultado del TratamientoRESUMEN
Surgeons at a Dutch wound clinic close open wounds with split-skin grafts. Concerns about the risk of postoperative complications in some patients led them to find an alternative option. Use of an extracellular matrix dressing was effective.