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1.
New Microbes New Infect ; 47: 100986, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35668841

RESUMEN

The safety and efficacy of tafenoquine administered as a 200 mg dose once per day on days 1, 2, 3, and 10 was evaluated over a 28-day period in mild-moderate COVID-19 patients. The primary endpoint was Day 14 clinical recovery from COVID-19 symptoms, defined as cough mild or absent, respiratory rate < 24 bpm, and no shortness of breath or fever. Following a successful futility analysis after n = 86 patients out of a target n = 275 were randomized, the study was terminated and unblinded early to facilitate planning for confirmatory studies. The proportion of patients not recovered on Day 14 was numerically decreased by 27% in the ITT population [8/45 v 10/42 not recovered in the tafenoquine and placebo arms, P = 0.60] and 47% in the PP population [5/42 v 9/41, P = 0.25]. Amongst individuals who recorded responses in an electronic diary at Day 28, all tafenoquine patients were recovered, whereas up to 12% of placebo patients exhibited lingering dyspnea. Time to clinical recovery from COVID-19 symptoms was accelerated in the tafenoquine arm by about 2-2.5 days. There were two COVID-19 related hospitalizations in the placebo arm and one in the tafenoquine arm. Mild, drug related adverse events occurred in 8.4% of individuals in the tafenoquine arm [v 2.4% in the placebo]. Although this trial was underpowered for the primary endpoint due to its early termination, the data are suggestive of a therapeutic benefit associated with tafenoquine administration in outpatients with mild to moderate COVID-19 disease, and larger studies are planned.

2.
Front Neuroendocrinol ; 47: 109-122, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28736323

RESUMEN

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions.


Asunto(s)
Encéfalo/inmunología , Desnutrición/inmunología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Efectos Tardíos de la Exposición Prenatal/inmunología , Animales , Conducta Animal/fisiología , Femenino , Lactancia/inmunología , Embarazo
3.
J Fish Biol ; 84(1): 267-72, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24383811

RESUMEN

A rapid non-destructive alternative to isolate DNA from an individual fish larva is presented, based on the suspension of epithelial cells through vortex forces, and the release of DNA in a heated alkaline solution. DNA from >6056 fish larvae isolated using this protocol has yielded a high PCR amplification success rate (>93%), suggesting its applicability to other taxonomic groups or sources when tissue amount is the limiting factor.


Asunto(s)
ADN/aislamiento & purificación , Peces , Reacción en Cadena de la Polimerasa/métodos , Animales , Células Epiteliales , Larva/genética , Manejo de Especímenes/métodos
4.
N Z Vet J ; 60(6): 315-28, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22913513

RESUMEN

Ryegrass staggers is a seasonal mycotoxicosis of grazing livestock characterised by tremors, in coordination and a staggering gait almost unaccompanied by physical lesions. Deaths occur only as a consequence of accident or starvation. Outbreaks, in summer and autumn, occur only on pasture in which endophyte (Neotyphodium lolii)-infected perennial ryegrass (Lolium perenne) predominates and usually on which animals are grazed intensively. Animals recover when moved to a different type of grazing or after rain has promoted pasture growth. The disease was recognised for 80 years before its cause was discovered as a consequence of a grazing trial of sheep on three ryegrass cultivars which happened to have three different levels of endophyte infection. The endophyte was first formally described as Acremonium loliae, later corrected to Acremonium lolii, and was finally placed in the genus Neotyphodium. It produces a number of secondary metabolites of which lolitrem B is the principal one causing ryegrass staggers symptoms. Ergopeptides are also produced which cause heat stress and lack of productivity. N. lolii is symptomless in the plant, seed borne and grows intercellularly in the aerial parts, mainly in reproductive tillers and leaf sheaths but sparsely in leaf blades. It dies in stored seed and infection rates of different ryegrass cultivars have depended on seed storage times during their production. In addition, N. Lolii produces insect feeding deterrents, among them peramine, which protects infected plants from pest predation. Because of this, control of ryegrass staggers by elimination of endophyte-infected ryegrass is not feasible in areas in which insect predation is a serious pasture problem. However, N. lolii strains vary in the secondary metabolites they produce allowing the selection of strains that produce desirable metabolites. By inoculating such strains into uninfected ryegrass plants it is possible to produce cultivars which do not cause ryegrass staggers but resist insect predation. This review aims to provide a comprehensive summary of the current understanding of the N. lolii / L. perenne symbiosis, the toxins it is known to produce, their effects on animals and plants and the strategies used to control their ill effects while maximising their beneficial ones.


Asunto(s)
Lolium/microbiología , Neotyphodium/fisiología , Intoxicación por Plantas/veterinaria , Simbiosis , Animales
5.
J Dairy Sci ; 94(4): 1961-6, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21426987

RESUMEN

The nutritional equivalency of grain plus whole plant silage from genetically modified corn plants containing the DAS-59122-7 (59122) event expressing the Cry34Ab1 and Cry35Ab1 proteins to grain and silage from a near-isogenic corn hybrid without this trait (control) was assessed using lactating dairy cows. Corn plants with event 59122 are resistant to western corn rootworm and tolerant to the herbicide active ingredient glufosinate-ammonium. Effects on feed intake, milk production, and milk composition were determined. The 59122 grain and the control grain were produced in 2005 from isolated plots in Richland, Iowa. Whole plant corn silage for the 59122 and control treatments were grown in isolated plots at the Kansas State University Dairy Center and ensiled in Ag-Bags. Thirty lactating Holstein cows blocked by lactation number, day of lactation, and previous energy-corrected milk production were used in a switchback design. All cows were fed diets that contained 22.7% grain plus 21.3% whole plant silage from either the 59122 or the control hybrid, in addition to 21% wet corn gluten feed, 12.3% protein mix, 8.0% whole cottonseed, and 14.7% alfalfa hay. Each period of the switchback trial included 2 wk for diet adjustment followed by 4 wk for data and sample collection. Milk samples (a.m. and p.m.) collected from 2 consecutive milkings of each collection wk were analyzed for fat, protein, lactose, solids-not-fat, milk urea nitrogen, and somatic cell count. Percentages of milk fat, protein, lactose, and solids-not-fat were not affected by dietary treatment. Yields of milk, 4% fat-corrected milk, energy-corrected milk, solids-corrected milk, and the concentrations and yields of milk fat, milk protein, milk solids, and milk lactose were not significantly different between treatments. Efficiencies of milk, fat-corrected milk, energy-corrected milk, and solids-corrected milk production also were not different when cows were fed crops from 59122 than when they were fed the control hybrid. Milk production efficiency averaged 1.48 and 1.50 kg/kg of dry matter intake for cows fed diets containing the control and 59122 corn, respectively. These data indicate that the nutritional value for milk production was not different between a diet containing grain plus whole plant corn silage produced from a 59122 corn hybrid versus a diet containing grain and corn silage from its near-isogenic control corn hybrid.


Asunto(s)
Bovinos/fisiología , Dieta/veterinaria , Lactancia/fisiología , Plantas Modificadas Genéticamente/genética , Zea mays , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , ADN de Plantas/análisis , Grano Comestible , Femenino , Ensilaje , Zea mays/genética
6.
Ann Surg Oncol ; 18(3): 733-7, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20882415

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (bev) in the neoadjuvant setting. We sought to explore the safety of neoadjuvant cisplatin/bev in a protocol for triple negative breast cancer (TNBC). MATERIALS AND METHODS: A total of 51 patients with confirmed TNBC were enrolled in a single-arm trial of neoadjuvant cisplatin plus bev. Of the 51 patients, 28 with confirmed TNBC were enrolled in our trial of single-agent neoadjuvant cisplatin. Two-sided Fisher exact test were used for comparing the 2 trials. RESULTS: The 51 patients received neoadjuvant protocol therapy with cisplatin/bev and underwent definitive local therapy. Breast conserving therapy (BCT) was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 patients (43%); 4 (8%) required explanation of expanders. Also, 28 patients completed neoadjuvant cisplatin therapy. BCT was performed in 13 (46%) and mastectomy with or without reconstruction in 15 (54%). Postoperative complications were reported in 11 patients (39%). None of the 5 reconstructions were lost. We compared all toxicities between the two trials (P = .81 NS), and wound healing related complications between the two trials (P = .10 NS). CONCLUSIONS: Cisplatin/bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically, use of expanders/implants may be problematic for patients treated with bev. However, this was a single-arm trial; randomized controlled studies will be needed to determine the optimal use of bevacizumab in the timing of breast cancer surgery.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Terapia Neoadyuvante , Complicaciones Posoperatorias , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Bevacizumab , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Biopsia del Ganglio Linfático Centinela , Tasa de Supervivencia , Resultado del Tratamiento
7.
Vaccine ; 28(34): 5597-604, 2010 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-20600512

RESUMEN

HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open-label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals >or=18 years of age, CD4 count >or=200 cells/mm(3), seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm(3), 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF arm reported transient grade >or=2 signs/symptoms (six grade 2, one grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb >or=10 mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF vs. control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 >or=350 cells/mm(3) (64%) than with CD4 <350 cells/mm(3) (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Infecciones por VIH/inmunología , Vacunas contra Hepatitis B/inmunología , Adulto , Formación de Anticuerpos , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Hepatitis B/inmunología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B/sangre , Vacunas contra Hepatitis B/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
8.
Clin Radiol ; 65(6): 453-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20451012

RESUMEN

AIM: To retrospectively assess the frequency of internal mammary lymph nodes (IMNs) in patients after mastectomy and tissue-expander reconstruction. MATERIALS AND METHODS: Statistical analysis was performed for all available data in patients with mastectomy and tissue-expander reconstruction from 2004-2007 (study group). The data were compared with that of a control population with mastectomy who did not have reconstruction (control group). Patients with recurrent breast cancers, previous breast reconstruction, surgeries performed at outside hospitals, no available pre- or postoperative computed tomography (CT) or magnetic resonance imaging (MRI) data, or inadequate imaging follow-up were excluded. RESULTS: There were eight patients in the study group (median age 50.5 years, seven breast cancers), and eight patients in the control group (median age 52 years, seven breast cancers). No patients had IMNs on their preoperative imaging examinations. New IMNs were present in postoperative imaging in seven of eight patients (7/8, 87.5%) in the study group. All of them were stable or decreased in size on subsequent imaging examinations. None of the patients in the control group had IMNs (0/8). CONCLUSION: IMNs are common on imaging after mastectomy and tissue-expander placement. The IMNs decreased or remained stable on follow-up imaging and may represent reactive nodes.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Mamoplastia/métodos , Mastectomía/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Espectroscopía de Resonancia Magnética , Arterias Mamarias , Persona de Mediana Edad , Estudios Retrospectivos , Dispositivos de Expansión Tisular , Tomografía Computarizada por Rayos X
9.
Br J Surg ; 97(3): 305-16, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20101646

RESUMEN

BACKGROUND: Although effective local control is the primary goal of surgery for breast cancer, the long-term aesthetic outcome is also important. Nipple-sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed. METHODS: The review was based on a PubMed search using the terms 'nipple-sparing' or 'subcutaneous mastectomy' and 'breast cancer'. RESULTS: Large pathological studies report occult nipple involvement with cancer in 5.6-31 per cent, reflecting variation in inclusion criteria. Recent clinical series with careful patient selection report local recurrence in less than 5 per cent of patients. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than 1 per cent. Nipple necrosis rates range up to 8 and 16 per cent for total and partial necrosis respectively. Variations in outcome result from differences in extent of resection, placement of incisions and type of breast reconstruction. CONCLUSION: Nipple-sparing mastectomy is an acceptable technique for women undergoing risk-reducing mastectomy. In the therapeutic setting, it may be offered to patients with smaller tumours far from the nipple and favourable pathological features. Women should be counselled about nipple necrosis and the potential for local recurrence.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía/métodos , Pezones/cirugía , Femenino , Humanos , Cuidados Intraoperatorios , Necrosis , Pezones/patología , Satisfacción del Paciente , Selección de Paciente , Medición de Riesgo , Sensación , Resultado del Tratamiento
10.
Mol Ecol Resour ; 10(1): 193-6, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21565009

RESUMEN

High-resolution melting analysis (HRMA) is a highly sensitive closed-tube genotyping method used primarily in clinical studies. As the method is rapid, inexpensive and amenable to high throughput, we decided to investigate its applicability to population studies. Small amplicons and unlabelled probes were used to genotype the nuclear genes, lactate dehydrogenase-A (ldh-A), myosin light chain-2 (mlc-2), acidic ribosomal phosphoprotein P0 (ARP) and calmodulin (CaM) in populations of swordfish, Xiphias gladius. Results indicate that HRMA is a powerful genotyping tool to study wild populations.

11.
J Anim Sci ; 87(4): 1254-60, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19098236

RESUMEN

A growth performance experiment was conducted to assess the feeding value of a double-stacked transgenic corn grain for growing-finishing pigs. The genetically modified corn grain contained event DAS-59122-7, which expresses the Cry34/35Ab1 binary insecticidal protein for the control of corn rootworm. This modified transgenic grain is resistant to western corn rootworm and is also tolerant to herbicides containing the active ingredient glufosinate-ammonium. The modified grain (59122), a nontransgenic near-isoline grain (control corn), and a commercial corn (Pioneer brand hybrid 35P12) were grown in a 2005 production trial in individually isolated plots that were located 201 m apart. A total of 108 pigs were allotted to corn-soybean meal diets containing 1 of the 3 grains as the sole source of corn. There were 3 pigs per pen and 12 replicate pens per treatment. Pigs were fed grower diets from 37 to 60 kg, early finisher diets from 60 to 90 kg, and late finisher diets from 90 to 127 kg. Within each phase, data for ADG, ADFI, and G:F were calculated. At the conclusion of the experiment, pigs were slaughtered and data for carcass quality were collected. Differences between 59122 and the control corn were evaluated, with statistical significance at P<0.05. No differences in ADG, ADFI, or G:F between pigs fed the control corn and pigs fed the modified corn were observed during the grower, early finisher, or late finisher phases. For the entire experimental period, no difference between pigs fed the control and the 59122 corn were observed for final BW (128.9 vs. 127.1 kg), ADG (1.02 vs. 1.00 kg), ADFI (2.88 vs. 2.80 kg), or G:F (0.356 vs. 0.345 kg/kg). Likewise, no differences in dressing percentage (76.48 vs. 76.30%), LM area (49.8 vs. 50.4 cm(2)), 10th-rib back fat (2.20 vs. 2.12 cm), and carcass lean content (52.9 vs. 53.4%) were observed between pigs fed the control and the 59122 corn grain. It was concluded that the nutritional value of the modified transgenic corn grain containing event DAS-59122-7 was similar to that of the nontransgenic near-isoline control.


Asunto(s)
Dieta/veterinaria , Alimentos Modificados Genéticamente/normas , Porcinos/fisiología , Zea mays/genética , Zea mays/metabolismo , Alimentación Animal/análisis , Animales , Composición Corporal/fisiología , Ingestión de Alimentos/fisiología , Femenino , Masculino , Plantas Modificadas Genéticamente/genética , Distribución Aleatoria , Glycine max/metabolismo , Porcinos/crecimiento & desarrollo , Porcinos/metabolismo , Aumento de Peso/fisiología
12.
Br J Surg ; 95(11): 1356-61, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18844271

RESUMEN

BACKGROUND: This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple-sparing mastectomy. METHODS: Two hundred consecutive skin-sparing mastectomy specimens without overt nipple involvement were evaluated. Demographic, preoperative pathology and imaging information was collected. Nipple specimens (2 x 2 x 2 cm) were sectioned at 3-mm intervals. Haematoxylin and eosin-stained slides were examined by a breast pathologist for involvement by tumour. Logistic regression analyses of 65 therapeutic procedures identified factors associated with occult involvement and created a predictive model. This was tested on specimens from a further 65 therapeutic procedures. RESULTS: Occult nipple involvement was noted in 32 (24.6 per cent) of 130 mastectomy specimens. In the training set, imaging diameter of the lesion and its distance from the nipple predicted nipple involvement on univariable analysis (P = 0.011 and P = 0.014 respectively). The multivariable logistic regression model was validated in the test set. The areas under the receiver-operating characteristic curve were 0.824 and 0.709 for the training and test sets respectively. CONCLUSION: Three-quarters of women undergoing mastectomy did not have occult nipple involvement. A clinical tool including tumour size and distance from the nipple has been developed to improve patient selection for nipple-sparing mastectomy.


Asunto(s)
Neoplasias de la Mama/patología , Mastectomía Subcutánea/métodos , Pezones/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Pezones/cirugía , Selección de Paciente , Estudios Prospectivos , Análisis de Regresión
13.
Ann Surg Oncol ; 15(12): 3384-95, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18726129

RESUMEN

BACKGROUND: Reports demonstrate improved survival of stage IV breast cancer patients with primary cancer resection. This may result from selection for surgery, rather than biological processes. METHODS: We performed matched-pair analysis that minimized potential bias in selecting surgery for primary cancer. Chart review was also performed of 5-year survivors to assess selection bias affecting breast surgery. RESULTS: 19,464 breast cancer patients were identified; 808 (4.2%) were stage IV: 622 were analyzed after eliminating wrong diagnoses or staging, and limiting patients to Massachusetts residents. Matched-pair analysis narrowed or eliminated apparent survival benefit associated with primary site surgery in several comparisons. When the impact of the sequence of systemic and surgical treatments was studied in stage IV patients, 90% 2-year survival occurred in patients receiving chemotherapy first, in contrast to receiving chemotherapy simultaneously with or after surgery, suggesting selection for delayed surgery after excellent response to initial chemotherapy. In bone metastases, the 2-year survival advantage occurred with chemotherapy before surgery; no difference in survival with or without surgery occurred when these treatments were simultaneous. Among 5-year survivors, frequency of primary site surgery after excellent response to systemic therapy, breast surgery in stage III patients incorrectly classified as stage IV, and frequency of oligo metastases all indicated selection bias. CONCLUSIONS: Case selection bias in primary breast cancer resection in state IV patients may explain most, if not all, the apparent survival advantage of such surgery.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Mastectomía/estadística & datos numéricos , Análisis por Apareamiento , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Mama/secundario , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Massachusetts , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sesgo de Selección , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
14.
Int J Gynecol Cancer ; 16(3): 1172-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16803502

RESUMEN

The objective of this study was to determine the response rate in chemonaive patients with inoperable, locally advanced, recurrent, or metastatic cervical cancer treated with pemetrexed (Alimta, LY231514), a multitargeted antifolate. The patients were treated with either 500 mg/m(2) (11 patients) or 600 mg/m(2) (24 patients) of pemetrexed, administered as a 10-min infusion on day 1 of a 21-day cycle. Patients receiving 500 mg/m(2) dose also received 5 mg/day oral folic acid supplementation beginning 2 days prior and ending on day 3 of each cycle. Of the 34 patients evaluable for efficacy, six patients (18%) had partial response, with median response duration of 3.8 months (range, 3.3-6.6 months). Twenty-four patients (71%) had stable disease, one patient (3%) had progressive disease, and three patients could not be assessed. Median overall survival was 15.2 months (range, 2.9-35.3+ months). Grade 4 hematologic toxicities consisted of neutropenia (37%), leukopenia (9%), anemia (6%), and thrombocytopenia (3%). One patient died of hypotensive shock associated with frank rectal hemorrhage that was considered to be related to the study drug. We conclude that pemetrexed therapy showed moderate activity, similar to other active agents, in the treatment of locally advanced or metastatic cervical cancer.


Asunto(s)
Carcinoma/tratamiento farmacológico , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma/mortalidad , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Femenino , Ácido Fólico/uso terapéutico , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Leucopenia/inducido químicamente , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neutropenia/inducido químicamente , Pemetrexed , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad
15.
Vet Rec ; 157(25): 805-10, 2005 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-16361474

RESUMEN

Outbreaks of pithomycotoxicosis (facial eczema), a hepatogenous photosensitisation caused by the mycotoxin sporidesmin, have affected ruminants in the Azores Islands of Portugal after warm, humid periods during late summer and autumn. Twenty-two outbreaks were recorded in cattle between 1999 and 2001, affecting 11.4 per cent of the animals in the affected herds, and in 2000 there was an outbreak in one sheep flock in which more than 20 per cent of the sheep died. The clinical signs included decreases in milk production, weight loss, photosensitisation and its sequelae, including death. The animals had high activities of gamma glutamyltransferase in their serum, and icterus and severe liver disease, including biliary hyperplasia and fibrosis, were found postmortem. The characteristic spores of the toxigenic saprophytic fungus Pithomyces chartarum were found on grass; all 381 isolates of the fungus were toxigenic for sporidesmin by elisa, and the results were confirmed by high-performance liquid chromatography analysis. Cattle from farms at greatest risk of pithomycotoxicosis were protected by supplementing their concentrate feed with zinc oxide, or using a slow-release intraruminal zinc bolus.


Asunto(s)
Ascomicetos/metabolismo , Brotes de Enfermedades/veterinaria , Eccema/veterinaria , Poaceae/microbiología , Rumiantes , Esporidesminas/toxicidad , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Eccema/epidemiología , Cara , Portugal/epidemiología , Estaciones del Año , Ovinos , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/microbiología , Esporas Fúngicas/aislamiento & purificación , Esporidesminas/aislamiento & purificación
16.
Artículo en Inglés | MEDLINE | ID: mdl-16124430

RESUMEN

Three hundred thirty-six stool samples from October 2001 through October 2002 were analyzed for the presence of intestinal parasites. Fifty-six of these (16.7%) were positive for a total of 66 parasites; 65/66 (98.5%) were detected by iodine and dimethyl sulfoxide-modified acid-fast (DMSO-mAFB) stained smears of fresh and formalin-ethylacetate sedimentation concentrated samples. Saline, iodine, and DMSO-mAFB stained smears of fresh stool samples alone detected significantly fewer parasites, finding only 50/66 (75.8%) (p < 0.05). Stool samples analyzed by trichrome stained specimens preserved in Zinc sulfate polyvinyl alcohol (Zinc PVA) detected only 41/ 66 (62.2%) of the parasites. In our study population, it was necessary to perform the National Committee for Clinical Laboratory Standard (NCCLS) recommended to accurately detect intestinal parasites. The concentration technique is simple and significantly increased the detection of intestinal parasites.


Asunto(s)
Colorantes , Pruebas Diagnósticas de Rutina/métodos , Dimetilsulfóxido , Heces/parasitología , Yodo , Manejo de Especímenes/métodos , Compuestos Azo , Preescolar , Pruebas Diagnósticas de Rutina/normas , Eosina Amarillenta-(YS) , Humanos , Lactante , Intestinos/parasitología , Verde de Metilo , Solventes , Manejo de Especímenes/normas , Tailandia , Oligoelementos
18.
Br J Cancer ; 91(6): 1190-4, 2004 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-15305194

RESUMEN

ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Estudios Retrospectivos , Transducción de Señal , Trastuzumab
19.
Indian J Med Res ; 119 Suppl: 213-20, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15232198

RESUMEN

BACKGROUND & OBJECTIVES: R proteins were first identified by Lancefield in group B Streptococcus (GBS) as resistant to trypsin at pH8 and sensitive to pepsin at pH2. The R4 protein found predominantly in type III and some type II and V invasive isolates conforms to these criteria. The Rib protein, although structurally and epidemiologically similar to R4, was reported as resistant to both proteases. We report here the gene encoding the R4 protein from a type III group B streptococcal isolate (76-043) well characterized in our laboratory. METHODS: Trypsin extracted GBS proteins were assayed for protease sensitivities by double-diffusion Ouchterlony using varying conditions for the enzyme pepsin. Standard haemoglobin assay was used to examine pepsin enzymatic activity. Thirty clinical isolates of varying protein profiles identified by double-diffusion from our reference strain laboratory were screened by PCR and Southern technique. SDS-PAGE gel purified R4 amino acid sequences were determined and used to design oligonucleotide primers for screening a 76-043 genomic library. RESULTS: R4 was sensitive to pepsin at pH2 but appeared resistant at pH4, the reported pH used for Rib. By standard haemoglobin assay and trypsin extract studies of R4 protein, pepsin was shown to be active at pH2, yet easily inactivated; assays of GBS surface proteins are critical at pH2. Of the amino acids initially sequenced from R4, 88 per cent (61/69) showed identity to Rib; the r4 nucleotide sequence was identical to that of rib. All isolates with strong positive protein reactions for R4 were positive in both PCR and Southern technique, whereas isolates expressing alpha, beta, R1/R4, and R5 (BPS) protein profiles were not. INTERPRETATION & CONCLUSION: Sequenced PCR products aligned with identity to the R4 and Rib nucleotide sequences and confirmed the identity of these proteins and their molecular sequences.


Asunto(s)
Proteínas Bacterianas/genética , Pepsina A/metabolismo , Streptococcus agalactiae/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Secuencia de Bases , ADN Bacteriano , Datos de Secuencia Molecular , Estándares de Referencia
20.
N Z Vet J ; 52(5): 205-15, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15768115

RESUMEN

Facial eczema (FE) is a costly problem to New Zealand pastoral agriculture, and has a detrimental impact on animal wellbeing. Incidence and severity of the disease can be reduced by grazing management and zinc prophylaxis. An additional strategy is to breed animals that are genetically resistant to intoxication with sporidesmin, the causative mycotoxin. This review summarises research findings on the inheritance of resistance of animals to FE, including evidence of among- and within-breed genetic variation, direct and correlated responses to selection, and identification of genetic markers and candidate genes for FE resistance.

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