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51.
EM Maier J Pongratz AC Muntau B Liebl U Nennstiel-Ratzel U Busch R Fingerhut B Olgemöller AA Roscher W Röschinger 《Clinical genetics》2009,76(2):179-187
Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C8) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C8; 7 for C8/C12) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS. 相似文献
52.
Silvio ST Tafuri Domenico DM Martinelli Giovanni GC Caputi Annamaria AA Arbore Cinzia CG Germinario Rosa RP Prato 《BMC health services research》2009,9(1):100-5
Background
Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service. 相似文献53.
Ross AA; Cooper BW; Lazarus HM; Mackay W; Moss TJ; Ciobanu N; Tallman MS; Kennedy MJ; Davidson NE; Sweet D 《Blood》1993,82(9):2605-2610
Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro. 相似文献
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AA Lapillonne FH Glorieux BL Salle PM Braillon M Chambon J Rigo G Putet J Senterre 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(S405):117-122
Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life. 相似文献
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58.
C. Boulanger NA Flavahan ZS Katusic K. Komori AA Vos and PM Vanhoutte MD Director 《Fundamental & clinical pharmacology》1990,4(5):525-538
Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings. 相似文献
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Hinsch E; Ponce AA; Hagele W; Hedrich F; Muller-Schlosser F; Schill WB; Hinsch KD 《Human reproduction (Oxford, England)》1997,12(8):1673-1681
Binding of mammalian spermatozoa to the zona pellucida and the induction of
the acrosome reaction are prerequisites for successful oocyte
fertilization. It has been postulated that xenobiotics that are released in
the environment as well as exposure to pharmaceutical medications may be
associated with reproductive problems in men and wildlife. Examining
physiological and non-physiological effects of particular compounds on
sperm functions requires high quality in-vitro test systems. We established
a reliable combined in-vitro test system with bovine gametes and evaluated
if aliquots of pooled post-thaw spermatozoa are suitable for examining
essential sperm functions. Using cryopreserved semen, the PSA-FITC/Hoechst
33258 staining procedure was applicable to evaluate the acrosomal status
and cell viability. In the bovine hemizona assay, hemizona indices revealed
no differences between cryopreserved and fresh semen. Treatment of
post-thaw bovine spermatozoa with progesterone (1 microM or bovine
follicular fluid (20%) induced the acrosome reaction from 12% (untreated
spermatozoa) to 25% (P < 0.001) and to 22% [corrected] (P < 0.01),
respectively. Incubation of both compounds (1 microM progesterone and 20%
follicular fluid) raised the percentage of acrosome-reacted spermatozoa to
30% (P < 0001). Our results demonstrate that cryopreserved semen can be
integrated into an in-vitro screening model for reproductive toxicology
testing. Pooled, cryopreserved bovine spermatozoa will thus permit
reproducible experiments for clinical and basic science purposes and may
also be applicable for the human system.
相似文献