Cerebrovascular reactivity after cessation of menopausal hormone treatment.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17ß-estradiol, or placebo [PLA]). RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Influence of post-insemination nutrition on embryonic development in beef heifers.

Previous studies have demonstrated that a decrease in nutrition immediately following AI reduces pregnancy success in beef heifers. The objective of this experiment was to determine if nutrient restriction following AI impacted early embryonic development among non-super ovulated heifers. Beef heifers in eight replications (Rep; Rep 1; n = 14, Rep 2; n = 15, Rep 3; n = 15, Rep 4; n = 14, Rep 5; n = 15, Rep 6; n = 15, Rep 7; n = 25, Rep 8; n = 25) across two locations (UMN, SDSU) were developed in a dry-lot and fed 125% NRC requirements from weaning to timed-AI (d 0). Heifers were timed-AI to a single sire in all replications. Immediately following AI, heifers were assigned, based on age, weight, and estrous response to one of two post-AI nutritional treatments. Half the heifers in each replication continued on the pre-insemination diet, serving as the control treatment (CON) and the remaining heifers were restricted to a sub-maintenance diet (RES). At UMN, heifers in the RES treatment were fed the same diet, but intake was limited to 80% NEm, while at SDSU, DMI remained the same, but diet composition was altered with the addition of straw to reduce NEm to 50% of requirements. On d 6, single embryos were collected nonsurgically and recovered embryos (CON; n = 46, RES; n = 42) were evaluated to determine quality (grade 1-9) and stage (1-4). Embryos were then stained and evaluated to determine the number of dead cells and total blastomeres. In Reps 1 through 6, concentrations of IGF-1 were assessed on d 0 and 6 and progesterone concentrations on d 4 and 6. Data were analyzed using the Mixed procedures of SAS. There were no treatment by Rep or treatment by location interactions for any embryo parameter evaluated, thus all data were pooled. Embryo stage and quality were improved (P < 0.01) in the CON (4.4 ± 0.16, 2.2 ± 0.19, respectively) compared to RES treatment (3.7 ± 0.16, 2.9 ± 0.19, respectively). Embryos in the CON treatment had greater total blastomeres (66.9 ± 5.05; P < 0.01) and tended to have a greater percentage of live cells (P < 0.10; 80.9 ± 4.19%) compared to RES (47.9 ± 5.41; 69.7 ± 4.39%, respectively). Progesterone and IGF-1 concentrations did not differ between treatments. In summary, nutrient restriction for 6 days immediately following AI resulted in poorer quality embryos that were delayed in stage of development, suggesting that immediate changes in nutritional status after insemination can alter early embryonic development.

Influence of estrus at fixed-time artificial insemination on early embryonic development in beef cattle.

It has been repeatedly demonstrated that estrous expression before fixed-time AI (TAI) results in increased pregnancy success. Therefore, the objective of this experiment was to determine if preblastocyst embryonic developmental characteristics differed from heifers that did or did not exhibit estrus before TAI. Beef heifers (n = 113) were synchronized using the 5-d CO-Synch + controlled internal drug release device with TAI on d 0. Before TAI, estrous expression was assessed twice daily. On d 6, single embryos were collected and visually evaluated to determine quality (International Embryo Transfer Society standards; 1-4, in which 1 = excellent/good and 4 = degenerate) and stage (1-9, in which 1 = unfertilized and 9 = expanded hatched blastocyst). Embryos were stained and evaluated to determine number of dead blastomeres, number of total blastomeres, and number of accessory sperm. Estrous expression before TAI did not affect the percent of embryos recovered (P = 0.59), number of dead cells (P = 0.99), or number of total cells (P = 0.25). However, heifers that exhibited estrus had increased mean (P = 0.03) and median accessory sperm numbers and (P = 0.01) percent live cells when compared with nonestrus heifers. Heifers that exhibited estrus also produced embryos that had a more advanced stage (P = 0.03) and improved quality (P = 0.04) when compared with those heifers not exhibiting estrus. When all heifers were evaluated, there was no correlation between circulating concentration of estradiol at TAI and embryo quality or embryo stage. There was a significant correlation between accessory sperm numbers and embryo quality (P = 0.01) and embryo stage (P < 0.01), such that as accessory sperm numbers increased, embryo quality and stage increased. In conclusion, exhibiting estrus before TAI resulted in improved embryo quality and advanced embryo stage on d 6 and increased the number of accessory sperm associated with the embryo.

The requirement of GnRH at the beginning of the five-day CO-Synch + controlled internal drug release protocol in beef heifers.

The objective of this study was to determine if the omission of GnRH at controlled internal drug release device (CIDR) insertion would impact pregnancy rates to timed AI (TAI) in beef heifers enrolled in a 5-d CO-Synch + CIDR protocol that used 1 PGF2α dose given at CIDR removal. Yearling beef heifers in Ohio in 2 consecutive breeding seasons (2011, n = 151, and 2012, n = 143; Angus × Simmental), Utah (2012, n = 265; Angus × Hereford), Idaho (2012, n = 127; Charolais), and Wyoming (2012, n = 137; Angus) were enrolled in the 5-d CO-Synch + CIDR protocol. At CIDR insertion (d -5), heifers were randomly assigned either to receive 100 µg GnRH (GnRH+; n = 408) or not to receive GnRH (GnRH-; n = 415). At CIDR removal (d 0 of the experiment), 25 mg PGF2α was administered to all heifers. All heifers were inseminated by TAI and given 100 µg GnRH 72 h after PGF2α (d 3). In heifers at the Ohio locations (n = 294), presence of a corpus luteum (CL) at CIDR insertion (d -5) was determined via assessment of progesterone concentrations (2011) and ovarian ultrasonography (2012). Subsequently, in both years, ovarian ultrasound was conducted on d 0 to determine the presence of a new CL. In this same subgroup of heifers, blood samples for progesterone analysis were collected on d 3 to assess luteal regression. Pregnancy diagnosis was performed between 32 and 38 d after TAI. At CIDR withdrawal, presence of a new CL was greater (P < 0.05) in the GnRH+ (55.8%, 82/147) than GnRH- (26.5%, 39/147) treatment. Incidence of failed luteal regression did not differ between the GnRH+ (3.4%) and GnRH- (0.7%) treatments. Pregnancy rate to TAI did not differ between the GnRH+ (50.5%) and GnRH- (54.9%) treatments. In conclusion, although the incidence of a new CL at CIDR removal was increased in the GnRH+ treatment, omission of the initial GnRH treatment in the 5-d CO-Synch + CIDR protocol did not influence TAI pregnancy rate in yearling beef heifers. In addition, a single dose of PGF2α at CIDR removal was effective at inducing luteolysis in yearling beef heifers enrolled in the 5-d CO-Synch + CIDR protocol, regardless of whether or not the initial GnRH treatment was given.

Comparison of three CIDR-based fixed-time AI protocols in beef heifers.

Several effective fixed-time AI (FTAI) protocols have been developed to facilitate AI in beef heifers that circumvent the need for estrus detection. Among these are the 5-d CO-Synch + controlled intravaginal progesterone insert (CIDR) protocol (5dCO), PGF2α (PG) 6-d CIDR protocol (PG-6dCIDR), and 14-d CIDR-PG protocol (14dCIDR-PG). Although each of these protocols varies in duration and approach to synchronizing estrus and ovulation, each has been reported as an effective method to facilitate FTAI in beef heifers. Therefore, the objective of this study was to compare FTAI pregnancy rates in beef heifers synchronized with these 3 CIDR-based protocols. Virgin beef heifers (n = 801) at 4 locations were synchronized with 1 of 3 protocols: 1) 5dCO, an injection of GnRH (100 µg) and insertion of a CIDR on d -5, PG (25 mg) and CIDR removal on d 0 with a second injection of PG (>4 h after CIDR removal) on d 0 and FTAI at 72 h after CIDR removal, 2) PG-6dCIDR, PG (25 mg) on d -9, GnRH (100 µg) and insertion of a CIDR on d -6, PG and CIDR removal on d 0, and FTAI at 66 h after CIDR removal, or 3) 14dCIDR-PG, a 14-d CIDR insert from d -30 to -16, PG (25 mg) on d 0, and FTAI at 66 h after PG. All heifers received an injection of GnRH (100 µg) concurrent with FTAI. Timing of treatment initiation was offset to allow all heifers to receive FTAI concomitantly and at random. Pregnancy success was determined between 35 and 40 d after FTAI by transrectal ultrasonography. Blood samples were collected before the beginning of each protocol and at the initiation of each protocol to determine estrous cycling status (77%). Data were analyzed using the GLIMMIX procedures of SAS. As expected, because of the duration of protocols, fewer heifers in the 14dCIDR-PG treatment were pubertal at initiation of synchronization than in the 5dCO (P < 0.05) and PG-6dCIDR (P = 0.10) treatments. Fixed-time AI pregnancy success did not differ between treatments (P = 0.14; 62.6%, 56.9%, and 53.3% for 5dCO, PG-6dCIDR, and 14dCIDR-PG, respectively). However, heifers that had reached puberty by initiation of synchronization had greater (P < 0.01) pregnancy success compared to heifers that were prepubertal (60.7% and 47.3%, respectively). In summary, all 3 protocols had similar FTAI pregnancy success, and puberty status had the greatest impact on pregnancy success.

Administration of a GnRH analog on day 9 of a 14-day controlled internal drug release insert with timed artificial insemination in lactating beef cows.

Many estrus synchronization protocols aim to induce a new follicular wave to improve response and enhance pregnancy rate. Our objectives were to determine the effectiveness of GnRH analog administered d 0 and 9 during an extended controlled internal drug release (CIDR) protocol to produce 2 follicular waves, induce cyclicity in anestrus cows, and evaluate the efficacy of a single 50-mg dose of PGF2α to initiate luteal regression on CIDR removal. Lactating beef cows (n = 779) at 3 locations (n = 247, location 1; n = 395, location 2; n = 137, location 3) were randomly assigned to 1 of 3 treatments. Cows in the 14-d 50 PG treatment received a CIDR (1.38 g progesterone) with 100 µg GnRH analog intramuscularly (i.m.) on d 0, 100 µg GnRH analog i.m. on d 9, and CIDR removal concurrent with 50 mg PGF2α i.m. on d 14. Cows in the 14-d 6-h PG treatment were assigned the same protocol as the 14-d 50 PG treatment except that 25 mg PGF2α i.m. was given on d 14 plus 25 mg PGF2α i.m. 6 ± 1 h later. Cows in the control treatment, 5-d CO-Synch + CIDR (5-d CO-Synch), received a CIDR concurrent with 100 µg GnRH analog i.m. on d 9, CIDR removal concurrent with 25 mg PGF2α i.m. on d 14, and 25 mg PGF2α i.m. 6 ± 1 h after first F2α injection. Cows in all treatments received 100 µg GnRH analog i.m. and timed AI (TAI) 72 ± 3 h after CIDR removal. Pregnancy status to TAI was determined by ultrasonography 37 to 40 d after TAI. Averaged over all locations, pregnancy rates to TAI for 14-d 50 PG, 14-d 6-h PG, and 5-d CO-Synch treatments were 58.2%, 46.8%, and 41.9%, respectively. Pregnancy rates to TAI were greater (P < 0.05) in 14-d 50 PG treatment than 14-d 6-h PGF2α and 5-d CO-Synch treatments. Cycling status at 2 locations (n = 243, location 1; n = 391, location 2) was determined from blood collected on d -7 and 0; cows with serum progesterone concentrations >1 ng/mL at either (or both) bleeding date were considered cyclic. Averaged over the 2 locations, there was a tendency (P = 0.06) for a greater number of cyclic animals to become pregnant to TAI in the 14-d 50 PG treatment (64.4%) than 5-d CO-Synch treatment (50.2%). The 14-d CIDR with GnRH analog on d 0 and 9 and a single 50-mg dose of PG i.m. at CIDR removal was a more efficacious protocol to maximize TAI pregnancy rates than the standard 5-d CO-Synch.

Predicting water table response to rainfall events, central Florida.

A rise in water table in response to a rainfall event is a complex function of permeability, specific yield, antecedent soil-water conditions, water table level, evapotranspiration, vegetation, lateral groundwater flow, and rainfall volume and intensity. Predictions of water table response, however, commonly assume a linear relationship between response and rainfall based on cumulative analysis of water level and rainfall logs. By identifying individual rainfall events and responses, we examine how the response/rainfall ratio varies as a function of antecedent water table level (stage) and rainfall event size. For wells in wetlands and uplands in central Florida, incorporating stage and event size improves forecasting of water table rise by more than 30%, based on 10 years of data. At the 11 sites studied, the water table is generally least responsive to rainfall at smallest and largest rainfall event sizes and at lower stages. At most sites the minimum amount of rainfall required to induce a rise in water table is fairly uniform when the water table is within 50 to 100 cm of land surface. Below this depth, the minimum typically gradually increases with depth. These observations can be qualitatively explained by unsaturated zone flow processes. Overall, response/rainfall ratios are higher in wetlands and lower in uplands, presumably reflecting lower specific yields and greater lateral influx in wetland sites. Pronounced depth variations in rainfall/response ratios appear to correlate with soil layer boundaries, where corroborating data are available.

Vibration safety limits for magnetic resonance elastography.

Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within a tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit, and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans.

Spatio-temporal directional filtering for improved inversion of MR elastography images.

Dynamic magnetic resonance elastography can visualize and measure propagating shear waves in tissue-like materials subjected to harmonic mechanical excitation. This allows the calculation of local values of material parameters such as shear modulus and attenuation. Various inversion algorithms to perform such calculations have been proposed, but they are sensitive to areas of low displacement amplitude (and hence low SNR) that result from interference patterns due to reflection and refraction. A spatio-temporal directional filter applied as a pre-processing step can separate interfering waves so they can be processed separately. Weighted combinations of inversions from such directionally separated data sets can significantly improve reconstructions of shear modulus and attenuation.

Asthma and IL-4 receptor alpha gene variants.

Linkage of allergy to chromosome 16 has been described in several studies, together with a positive association with interleukin 4 receptor alpha gene variants. Our aim was to replicate these findings in a sample of German and Swedish families recruited through sib-pairs affected by bronchial asthma. None of the markers showed linkage with the main phenotype of asthma or with total serum IgE. Seropositivity to D. pteronyssinus showed borderline significance in a region flanking the IL4Ralpha location. Single nucleotide polymorphisms (SNPs) leading to the protein exchanges I50V, E375A, C406R, S478P and Q551R in the IL-4 receptor alpha were examined for allele sharing in sibs with asthma. Multiple regression analysis was performed for association with total serum IgE and specific IgE. Allele sharing of IL4Ralpha SNPs in asthmatic children was not significantly increased for any of the examined SNPs except for the intracytoplasmatic polymorphism 551R (0.79 vs. 0.84 expected, P = 0.044). The variants 50V, 478P and 551R were associated with slightly increased, and 375A and 406R with decreased total IgE levels, all at a non-significant level. None of the examined IL4Ralpha variants were correlated to asthma severity. In summary, a single gene effect of IL4Ralpha variants or any other gene on chromosome 16 could not be shown in this selected population of children with asthma. As there could be interactions with multiple genetic and environmental factors, IL4Ralpha could still be involved in asthma pathogenesis.

Magnetic resonance elastography: non-invasive mapping of tissue elasticity.

Magnetic resonance elastography (MRE) is a phase-contrast-based MRI imaging technique that can directly visualize and quantitatively measure propagating acoustic strain waves in tissue-like materials subjected to harmonic mechanical excitation. The data acquired allows the calculation of local quantitative values of shear modulus and the generation of images that depict tissue elasticity or stiffness. This is significant because palpation, a physical examination that assesses the stiffness of tissue, can be an effective method of detecting tumors, but is restricted to parts of the body that are accessible to the physician's hand. MRE shows promise as a potential technique for 'palpation by imaging', with possible applications in tumor detection (particularly in breast, liver, kidney and prostate), characterization of disease, and assessment of rehabilitation (particularly in muscle). We describe MRE in the context of other recent techniques for imaging elasticity, discuss the processing algorithms for elasticity reconstruction and the issues and assumptions they involve, and present recent ex vivo and in vivo results.

Treatment of primary monosymptomatic nocturnal enuresis with desmopressin: predictive factors.

OBJECTIVE: To investigate predictive factors for the outcome of treatment of primary monosymptomatic nocturnal enuresis (PMNE) with desmopressin. PATIENTS AND METHODS: Data from a large open multicentre study were analysed. The study comprised 399 children with PMNE who were recruited for long-term desmopressin treatment. Before treatment a history was taken and the children observed for 4 weeks. After a 6-week dose-titration period with desmopressin, the children were classified into four groups depending on the response rate. RESULTS: The children who improved during desmopressin treatment were older, had fewer wet nights during the observation period and had only one wet episode during the night, mostly after midnight. Many of them did not require the maximum dose of desmopressin to become dry. No hereditary factor for the response to desmopressin was found. CONCLUSION: Those most likely to be permanently dry with desmopressin treatment are older children who respond to 20 microg desmopressin and who do not wet frequently.

[Can homeopathy be integrated in a university hospital?]. / Homöopathie an der Universität: Ist eine Integration möglich?

BACKGROUND AND OBJECTIVE: The Dr. von Hauner Children's Hospital Munich has conducted a pilot project for 4 years, aiming at the integration of homeopathic concomitant treatment into daily clinical practice. This study was carried out to clarify whether the project is successful and accepted by physicians, nurses, and parents. METHODS: Questionnaires, all standardized and anonymous, were handed out to 137 physicians, 212 nurses and paramedics, and 1,048 parents of children treated at the hospital. RESULTS: 69% of the physicians appreciated concomitant homeopathic treatments, more than 60% believed the integration of homeopathy is suggestive, 75% saw a need for clinical research in homeopathy. 25% of the staff now had a more positive view towards homeopathy. 63% of the parents appreciated concomitant treatment, but only 19% are willing to participate in double-blind studies. CONCLUSIONS: Integration of homeopathy in a university hospital is possible. Therapeutic work should be accompanied by scientific research.

A novel polymorphism in the 5' promoter region of the human interleukin-4 receptor alpha-chain gene is associated with decreased soluble interleukin-4 receptor protein levels.

Interleukin (IL)-4 exerts its biological effects through binding to the IL-4 receptor (IL4R) complex, plays a central role in stimulating B-cell differentiation, and is crucial for the development of T helper 2 cells. Recently, a soluble form of the human IL4R alpha chain (sIL4R alpha), which is produced by alternate mRNA splicing of exon 8, was discovered. sIL4R is thought to play an important role in either enhancing or inhibiting IL-4 signalling. We analyzed the 5' promoter region of the human IL4R alpha-chain gene (IL4RA) of healthy volunteers by DNA sequencing and found three novel single-nucleotide polymorphisms (SNPs; T-890C, T-1914C, C-3223T) and one novel short tandem repeat [(CAAAA)(5-7)-3600]. The two common promoter region SNPs T-1914C and C-3223T as well as six known coding SNPs in the IL4RA gene were genotyped in healthy blood donors by PCR with sequence-specific primers; total sIL4R levels were measured by ELISA. Results revealed a highly significant association of the -3223T variant with lowered sIL4R levels (two-tailed t-test, P=0.0002). Results remained highly significant after Bonferroni adjustment for multiple comparisons (P=0.0017). Moreover, the C-3223T variant was found to be in strong linkage disequilibrium with the extracellular 150V variant (P<0.001), which was recently described to be associated with atopic asthma in a Japanese population. Since this novel IL4RA promoter region SNP is common (allele frequency 29.8%), we conclude that it may be of importance for the genetic regulation of the IL-4 signalling pathway.

Elucidation of the role of functional amino acid residues of the small sialidase from Clostridium perfringens by site-directed mutagenesis.

Bacterial sialidases represent important colonization or virulence factors. The development of a rational basis for the design of antimicrobials targeted to sialidases requires the knowledge of the exact roles of their conserved amino acids. A recombinant enzyme of the 'small' (43 kDa) sialidase of Clostridium perfringens was used as a model in our study. Several conserved amino acids, identified by alignment of known sialidase sequences, were altered by site-directed mutagenesis. All recombinant enzymes were affinity-purified and the enzymatic characteristics were determined. Among the mutated enzymes with modifications in the environment of the 4-hydroxyl group of bound sialic acids, D54N and D54E exhibited minor changes in substrate binding. However, a reduced activity and changes in their pH curves indicate the importance of a charged group at this area. R56K, which is supposed to bind directly to sialic acids as in the homologous Salmonella typhimurium sialidase, showed a 2500-fold reduced activity. The amino acids Asp-62 and Asp-100 are probably involved in catalysis, indicated by reduced activities and altered temperature and pH curves of mutant enzymes. Exchanging Glu-230 with threonine or aspartic acid led to dramatic decreases in activity. This residue and Y347 are supposed to be crucial for providing a suitable environment for catalysis. However, unaltered pH curves of mutant sialidases exclude their direct involvement in protonation or deprotonation events. These results indicate that the interactions with the substrates vary in different sialidases and that they might be more complex than suggested by mere static X-ray structures.

Visualization of a cytoskeleton-like FtsZ network in chloroplasts.

It has been a long-standing dogma in life sciences that only eukaryotic organisms possess a cytoskeleton. Recently, this belief was questioned by the finding that the bacterial cell division protein FtsZ resembles tubulin in sequence and structure and, thus, may be the progenitor of this major eukaryotic cytoskeletal element. Here, we report two nuclear-encoded plant ftsZ genes which are highly conserved in coding sequence and intron structure. Both their encoded proteins are imported into plastids and there, like in bacteria, they act on the division process in a dose-dependent manner. Whereas in bacteria FtsZ only transiently polymerizes to a ring-like structure, in chloroplasts we identified persistent, highly organized filamentous scaffolds that are most likely involved in the maintenance of plastid integrity and in plastid division. As these networks resemble the eukaryotic cytoskeleton in form and function, we suggest the term "plastoskeleton" for this newly described subcellular structure.

Studies on linkage and association of atopy with the chromosomal region 12q13-24.

BACKGROUND: Several studies have shown linkage of bronchial asthma, allergic rhinitis and total serum IgE concentration to the chromosomal region 12q13-24 in ethnical diverse populations. This region harbours a number of candidate genes for asthma and atopy, including stem cell factor (SCF), leukotriene A4 hydrolase (LTA4H), thyroid receptor 2 (TR2), and signal transducer and activator of transcription 6 (STAT6). However, the same region was shown as well to be linked to other diseases with inflammatory character. So far no variants in any of these genes have been published which would allow association studies and confirm the pathogenicity of any of these genes. OBJECTIVE: We wanted to test for linkage of the chromosomal region 12q13-24 with the atopic phenotype without regard to clinical manifestations. Furthermore we screened for common nucleotide polymorphisms in candidate genes to enable association studies. METHODS: We employed sib-pair linkage analysis and transmission disequilibrium testing with regard to four highly polymorphic microsatellite markers in 12q13-24 in atopic nuclear families. In addition, we looked for polymorphisms in the genes coding for SCF, LTA4H, TR2 and STAT6 performing SSCP-analysis and direct genomic sequencing. RESULTS: We found no evidence for linkage of the genomic region 12q13-24 to elevated total serum IgE levels, specific sensitization to common inhalant allergens or atopy. Furthermore we identified three nucleotide polymorphisms including one common variant in the gene coding for SCF. No association of this polymorphism and any of the atopic phenotypes was seen. CONCLUSION: We conclude from our data that genes in the chromosomal region 12q13-24 and in particular SCF are unlikely to exert a major effect on the induction of the atopic phenotype in our Caucasian population. However, we did not focus on the asthmatic and thereby inflammatory aspect of atopy which might explain these results in contradiction to previous studies.

Economic analysis of a phase III study of G-CSF vs placebo following allogeneic blood stem cell transplantation.

Hematopoietic colony-stimulating factors (CSF) decrease the duration of neutropenia following stem cell transplantation (SCT). With CSF-mobilized allogeneic blood SCT (alloBSCT), the yields of CD34+ cells are several-fold higher than in other SCT settings, raising concern that post-transplant CSF use may be unnecessary. In this study, we estimate the resource and cost implications associated with CSF use following alloBSCT. A cost identification analysis was conducted for 44 patients on a randomized, double-blind placebo-controlled trial of G-CSF following alloBSCT. Study drug was given daily until an absolute neutrophil count (ANC) > or = 1000 cells/microl. Billing information from the time of transplant to day +100 was analyzed. The median number of days to an ANC > or = 500 cells/microl was shorter in the G-CSF arm, 10.5 days vs 15 days (P < 0.001), while platelet recovery and rates of acute graft-versus-host disease (GVHD) and survival were similar. Resource use was similar, including days hospitalized, days on antibiotics, blood products transfused and outpatient visits. Total median post-transplant costs were $76577 for G-CSF patients and $78799 for placebo patients (P = 0.93). G-CSF following allogeneic blood SCT decreased the median duration of absolute neutropenia and did not incur additional costs, but did not result in shorter hospitalizations, or less frequent antibiotic use.

A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation.

Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT. Fifty-four patients with hematologic malignancies undergoing a related, HLA-matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10 microg/kg or placebo starting on the day of transplantation. A minimum of 3 x 10(6) CD34(+) cells/kg in the allograft was required for transplantation. All patients received a standard preparative regimen and a standard regimen for the prevention of graft-versus-host disease (GVHD). The median time to achieve an absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days (range, 9-20 days) for patients who received filgrastim compared with 15 days (range, 10-22 days) for patients who received placebo (P =.0082). The median time to achieve a platelet count greater than 20 x 10(9)/L was 13 days (range, 8-35 days) for patients who received filgrastim compared with 15.5 days (range, 8-42 days) for patients who received placebo (P =.79). There were no significant differences for red blood cell transfusion independence, the incidence of acute GVHD, or 100-day mortality between the groups. The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT.

Tissue characterization using magnetic resonance elastography: preliminary results.

The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for noninvasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves.