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1.
J Pediatr Urol ; 15(1): 77.e1-77.e7, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30482499

ABSTRACT

INTRODUCTION: Multicystic dysplastic kidney (MCDK) is the most common type of renal cystic disease. It is associated with urinary tract abnormalities in the contralateral kidney in up to 30% of cases, most commonly vesicoureteral reflux (VUR). OBJECTIVES: The objective of this study was to describe the incidence and selected issues in management and evolution for each VUR grade in the contralateral kidney of patients with unilateral MCDK, in order to strengthen the scientific basis regarding the need for voiding cystourethrography (VCUG) screening. METHODS: A comprehensive search of standard and gray literature was performed. Full-text screening, data abstraction, and quality appraisal were conducted in duplicates. Included studies reported a primary diagnosis of unilateral MCDK with contralateral VUR determined by VCUG. Articles had to include a distribution of VUR grade to meet the eligibility criteria. RESULTS: From 698 retrieved articles, 37 studies enrolling 2057 patients were analyzed. Of the patients, 80% were male; 50% had left unilateral MCDK; and 87% were diagnosed prenatally. A total of 1800 patients had VCUG, of whom 303 had VUR (weighted proportion: 17%; 95% confidence interval [CI]: 14-20%). Weighted proportions of VUR were 9%, 7%, and 17% for grades I-II, III-V, and I-V, respectively. Of the patients, 99% (95% CI: 97-100%) were on continuous antibiotic prophylaxis (CAP) and 18% (95% CI: 8-37%) had urinary tract infections (UTIs), with a higher rate of UTIs (23% vs 10%) in patients with dilating (grades III-V) VUR, over a mean follow-up of 40 months. In patients with dilating VUR, reflux resolved or downgraded to grade I in 52% (95% CI: 37-67%) of patients, and 32% (95% CI: 19-49%) had surgical correction of VUR. CONCLUSIONS: Among patients with unilateral MCDK, 17% have VUR in the contralateral kidney, 41% of which is dilating VUR. Of the cases with dilating VUR, half will resolve or downgrade to grade I during follow-up; 23% will develop a UTI despite CAP; and one-third will undergo ureteral re-implantation. While many physicians may thus choose to forego routine VCUG screening of the single functional kidney, shared decision-making with the patient's caregivers is currently recommended, where the risks and benefits of the different approaches can be discussed. The data from this analysis can help inform the discussions.


Subject(s)
Multicystic Dysplastic Kidney/complications , Vesico-Ureteral Reflux/epidemiology , Vesico-Ureteral Reflux/etiology , Child , Female , Humans , Incidence , Male , Vesico-Ureteral Reflux/pathology
2.
Leukemia ; 28(11): 2188-96, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24699307

ABSTRACT

Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average increase in ALC was 66%, and in>40% of patients the ALC peaked within 24 h of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in the LN, bone marrow and spleen decreased irrespective of the relative change in ALC. Whole-blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphocytosis/chemically induced , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Receptors, Antigen, B-Cell/antagonists & inhibitors , Signal Transduction/drug effects , Adenine/analogs & derivatives , Aged , Blood Viscosity/drug effects , Female , Hemoglobins/metabolism , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Lymphocyte Count , Male , Models, Biological , Piperidines , Tumor Burden/drug effects
3.
J Appl Microbiol ; 108(4): 1136-44, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19732215

ABSTRACT

AIMS: Ornithogalum dubium is a natural host of the soft rot pathogen Pectobacterium carotovorum ssp. carotovorum (Pcc). The present study was aimed to develop a quantification system for Pcc expressing a gfp reporter gene, using fluorescent activated cell sorter (FACS) in planta. METHODS AND RESULTS: Several calibration steps were required to distinctly gate the GFP-labelled bacteria at FL1 mode and count the bacteria. To validate the bacterial counts obtained by FACS analysis, an internal standard of polystyrene green fluorescent microsphere beads was employed, resulting in high correlation with serial dilutions and plate counting. This allowed quantification of the bacteria, with no further need to culture, dilute or plate the cells. Micropropagation tools were developed to produce uniform plantlets of O. dubium, which were either inoculated with increasing concentrations of Pcc or elicited for resistance towards Pcc using methyl jasmonate. The rapid counting procedure allowed recovering, gating and counting the bacterial population in planta, separately from the plant cells background and from the microsphere beads. CONCLUSIONS: The FACS based quantification approach of Pcc was found accurate, reproducible and time saving, thus useful for counting bacteria in planta. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of time- and cost-saving approach for Pcc quantification with efficient screening tools during early stages of micropropagation may facilitate the preliminary process of selection for resistant cultivars.


Subject(s)
Bacterial Load/methods , Flow Cytometry , Green Fluorescent Proteins/genetics , Ornithogalum/microbiology , Pectobacterium carotovorum/genetics , Pectobacterium carotovorum/metabolism , Acetates/pharmacology , Cyclopentanes/pharmacology , Ornithogalum/drug effects , Oxylipins/pharmacology , Plant Growth Regulators/pharmacology
4.
J Biotechnol ; 26(1): 83-97, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1368973

ABSTRACT

The adoption of plant cell cultures as an industrial process depends greatly on the economics of such a process. The multicycle or draw-fill culture technique is one method for improving the productivity and, hence, cost of a process. Mathematical models have been devised for the functional relationships between the nominal costs of biomass and secondary metabolites and the plant cell growth characteristics in a multicycle growth system. The models were used to evaluate the data obtained with cultures of Dioscorea deltoidea (which produces diosgenin) and Panax ginseng, grown in various types of bioreactors. The multicycle system gave an increase of 1.5-2 in biomass productivity compared with batch culture, but was probably only commercially viable if the cost of the process in the bioreactor was at least 30 times that of the medium and if an inoculum of about 30% of the culture of the previous cycle was left in the bioreactor. In the multicycle system incompletely utilised nutrient or metabolite accumulation can only reach 1.43 times or less that of the initial values. With the P. ginseng culture, about 75% of the calculated maximum cell packing density per fresh weight (approximately 530 g 1-1) in this regime was achieved. The possibility of growth in the standard bioreactor of a shear sensitive type culture was shown with a marine impeller speed up to 330 cm s-1.


Subject(s)
Cells, Cultured , Plant Cells , Biotechnology , Cell Division/drug effects , Culture Media , Diosgenin/metabolism , Ecology , Kinetics , Models, Theoretical
6.
Proc Natl Acad Sci U S A ; 71(8): 3006-8, 1974 Aug.
Article in English | MEDLINE | ID: mdl-4153283

ABSTRACT

Levels of three adrenal catecholamine synthesizing enzymes and isolation-induced fighting behavior were studied in two related sublines of the Balb/c inbred mouse strain. Enzyme levels were twice as high in the adrenals of Balb/cJ mice as in those of the Balb/cN mice; heterozygous progeny were intermediate between their parents in the levels of the three enzymes. These sublines also showed marked differences in their fighting behavior after a 2-week isolation period. Balb/cJ mice fought immediately after presentation of an intruder mouse, while Balb/cN mice did not fight at any time during the test. Heterozygous progeny behaved more like the Balb/cN (non-fighters). Analysis of F(2) mice suggested that the differences in fighting behavior were determined by a single gene, with fighting being recessive.


Subject(s)
Aggression , Catecholamines/biosynthesis , Genotype , Hybridization, Genetic , Mice, Inbred BALB C/metabolism , Adrenal Glands/enzymology , Animals , Dopamine beta-Hydroxylase/metabolism , Genes, Recessive , Genetics, Behavioral , Humans , Male , Mice , Motor Activity , Phenylethanolamine N-Methyltransferase/metabolism , Reaction Time , Species Specificity , Tyrosine 3-Monooxygenase/metabolism
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