Safety of bone marrow aspiration and biopsy in severely thrombocytopenic patients.

PURPOSE: To assess the safety of fluoroscopically guided drill-assisted bone marrow aspirate and biopsy in severely thrombocytopenic patients. MATERIALS AND METHODS: The study was approved by the IRB with waiver of informed consent. Retrospective review of 111 bone marrow aspirate and biopsies (BMAB) performed in 94 patients who received a CT scan which included the pelvis and biopsy site within the 7 days following the BMAB. The 94 patients were subdivided based on their platelet count: severe thrombocytopenia (< 20 platelets × 109/L), thrombocytopenia (20-50 platelets × 109/L), and control (> 50 platelets × 109/L). The procedure report was reviewed for sedation time, aspirate volume, and aggregate size of core biopsy specimens. The electronic medical record was reviewed for specimen adequacy; pathologic diagnosis; body mass index; pre- and post-procedure labs including platelet count, hemoglobin (HGB), hematocrit (HCT), prothrombin time (PT), and international normalized ratio (INR) levels; post-procedural transfusion; and complications including mortality at 30 and 90 days. CT scans were independently reviewed by 2 fellowship-trained radiologists for the presence of post-procedural hemorrhage. RESULTS: There was no significant difference in CT-identified post-procedural hematoma, or change in the hemoglobin and hematocrit levels pre- and post-procedure between the three groups. There was no significant difference in complication rate or all-cause mortality. There was a significant difference in transfusion at 30 days with thrombocytopenic and severely thrombocytopenic patients more likely to receive transfusion within the 30 days post-procedure. CONCLUSION: Fluoroscopically guided BMAB can be safely performed in patients with severe thrombocytopenia.

Biological control of Meloidogyne spp. in glasshouse-grown chrysanthemum.

Root-knot nematodes (Meloidogyne spp.) are a major problem in soil-based glasshouse-grown chrysanthemums. To combat root-knot nematodes in the glasshouse, the soil is typically steamed every 5-6 production cycles. However, this method is expensive, environmentally unfriendly and reduces resistance and resilience of the soil against pathogens and pests. Here, we added biological pesticides/a basic substance and biostimulants both individually and in combination to determine individual or interactive effects against damage by root-knot nematodes in chrysanthemums. We found that the application of biological nematicides derived from garlic extract, the basic substance chitosan HCl and biostimulants comprised of sea minerals and plant oils correlated with reduced root-knot nematode damage. These effects may have been due to direct effects against the nematodes or through indirect effects such as increased resistance and resilience of the plants. Overall, the biostimulants increased the total number of free-living nematodes in the soil, which could lead to a beneficial increase in nutrient cycling in the soils. Our results demonstrate that biological reagents show promise in reducing root-knot nematode damage in glasshouse-grown chrysanthemum and may lead to more resistance and resilient soils.

Oral health and risk of colorectal cancer: results from three cohort studies and a meta-analysis.

BACKGROUND: While studies have shown that poor oral health status may increase the risk of cancer, evidence of a specific association with the risk of colorectal cancer (CRC) is inconclusive. We evaluated the association between oral health and CRC risk using data from three large cohorts: the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Southern Community Cohort Study (SCCS), and carried out a meta-analysis of results from other relevant published studies. PATIENTS AND METHODS: This study applied a nested case-control study design and included 825 cases/3298 controls from the SMHS/SWHS and 238 cases/2258 controls from the SCCS. The association between oral health status (i.e. tooth loss/tooth decay) and CRC risk was assessed using conditional logistic regression models. A meta-analysis was carried out based on results from the present study and three published studies. RESULTS: We found that tooth loss was not associated with increased risk of CRC. ORs and respective 95% CIs associated with loss of 1-5, 6-10, and >10 teeth compared with those with full teeth are 0.87 (0.69-1.10), 0.93 (0.70-1.24), and 0.85 (0.66-1.11) among SMHS/SWHS participants; and 1.13 (0.72-1.79), 0.87 (0.52-1.43), and 1.00 (0.63-1.58) for those with loss of 1-4, 5-10, and >10 teeth among SCCS participants. Data regarding tooth decay were available in the SCCS, but were not associated with CRC risk. Meta-analysis confirmed the null association between tooth loss/periodontal disease and CRC risk (OR 1.05, 95% CI 0.86-1.29). CONCLUSION: In this analysis of three cohorts and a meta-analysis, we found no evidence supporting an association between oral health and CRC risk.

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

STUDY QUESTION: Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry? SUMMARY ANSWER: Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women. PARTICIPANTS AND SETTING: We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche. MAIN RESULTS: For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results. STUDY FUNDING/COMPETING INTERESTS: This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

Percutaneous CT-Guided Core Needle Biopsies of Head and Neck Masses: Technique, Histopathologic Yield, and Safety at a Single Academic Institution.

BACKGROUND AND PURPOSE: CT-guided head and neck biopsies can be challenging due to the anatomy and adjacent critical structures but can often obviate the need for open biopsy. A few studies and review articles have described approaches to biopsy in the head and neck. This retrospective study evaluated technical considerations, histopathologic yield, and safety in CT-guided head and neck core needle biopsies. MATERIALS AND METHODS: A retrospective review of head and neck biopsies performed from January 2013 through December 2019 was conducted. Clinical diagnosis and indication, patient demographics, mass location and size, biopsy needle type, technical approach, dose-length product, sedation details, complications, diagnostic histopathologic yield, and the use of iodinated contrast were recorded for each case. RESULTS: A total of 27 CT-guided head and neck core needle biopsies were performed in 26 patients. The diagnostic sample rate was 100% (27/27). A concordant histopathologic diagnosis was obtained in 93% (25/27) of cases. There was a single complication of core needle biopsy, a small asymptomatic superficial hematoma. CONCLUSIONS: Percutaneous CT-guided biopsy of deep masses in the head and neck is safe and effective with careful biopsy planning and has a high diagnostic yield that can obviate the need for open biopsy.

A genomewide scan for quantitative trait loci underlying areal bone size variation in 451 Caucasian families.

BACKGROUND: Bone size is an important determinant of bone strength and is under strong genetic control. OBJECTIVE: To identify quantitative trait loci (QTL) for areal bone size variation, a large-scale genomewide linkage scan was carried out in 451 Caucasian families. PARTICIPANTS AND METHODS: Of 4124 people with phenotypes, 3899 were genotyped with 410 microsatellite markers. Multipoint linkage analyses were carried out in the entire sample, as well as in men and women separately. Potential epistatic interactions between identified genomic regions were also assessed. RESULTS: Several potentially important genomic regions were identified, such as 8q24 for hip bone size (logarithm of the ratio of the odds that two loci are linked (LOD) 3.27) and 2p24 (LOD 2.04) for spine bone size. 8q24 may also interact with 19p13 to affect hip bone size. Several sex-specific QTL were also detected, such as 14q21 (LOD 2.94) for wrist bone size in women and 16q12 (LOD 2.19) for hip bone size in men. CONCLUSIONS: Together with previous findings, this study has further delineated the genetic basis of bone size and laid a foundation for future studies to eventually elucidate the mechanisms of bone size regulation and associated fracture risks.

Vitamin D receptor gene polymorphisms are linked to and associated with adult height.

BACKGROUND: The vitamin D receptor (VDR) gene is important to human stature, as it mediates metabolic pathways, calcium homeostasis, and phosphate homeostasis, which influence growth. METHODS: We examined the relationship between VDR and adult height in 1873 white subjects from 406 nuclear families. Four SNPs, namely -4817A/G at intron 1, FokI C/T at exon 2 start codon, BsmI A/G at intron 8, and TaqI T/C at exon 9 in VDR were tested for linkage and association with adult height variation by the program QTDT (quantitative transmission disequilibrium test). The bT haplotype of the BsmI and TaqI loci was further tested for its association with height in unrelated samples randomly chosen from the 406 nuclear families by traditional population association methods. RESULTS: All four tested SNPs were linked to adult height. Within family associations with height were detected at BsmI and TaqI loci (p = 0.048 and 0.039, respectively). Analyses based on BsmI/TaqI haplotypes also revealed evidence for linkage (p = 0.05) and association (p = 0.001) with height. The bT haplotype was significantly associated with higher adult height (p = 0.033, within family association test). Such an association might be female specific and influenced by menstrual status. CONCLUSIONS: Our results strongly suggest that VDR may be linked to and associated with adult height variation in white populations.

A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases.

BACKGROUND: The haplotype based association method offers a powerful approach to complex disease gene mapping. In this method, a few common haplotypes that account for the vast majority of chromosomes in the populations are usually examined for association with disease phenotypes. This brings us to a critical question of whether rare haplotypes play an important role in influencing disease susceptibility and thus should not be ignored in the design and execution of association studies. METHODS: To address this question we surveyed, in a large sample of 1873 white subjects, six candidate genes for osteoporosis (a common late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb, and covered a total of 377 kb of the DNA sequence. RESULTS: Our empirical data demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with frequencies of 1.1% and 2.9%, respectively, had significant effects on osteoporosis phenotypes (p = 4.2 x 10(-6) and p = 1.6 x 10(-4), respectively). Large phenotypic differences (4.0 approximately 5.0%) were observed between carriers of these rare haplotypes and non-carriers. Carriers of the two rare haplotypes showed quantitatively continuous variation in the population and were derived from a wide spectrum rather than from one extreme tail of the population phenotype distribution. CONCLUSIONS: These findings indicate that rare haplotypes/variants are important for disease susceptibility and cannot be ignored in genetics studies of complex diseases. The study has profound implications for association studies and applications of the HapMap project.

Ultra-wide bore 900 MHz high-resolution NMR at the National High Magnetic Field Laboratory.

Access to an ultra-wide bore (105 mm) 21.1 T magnet makes possible numerous advances in NMR spectroscopy and MR imaging, as well as novel applications. This magnet was developed, designed, manufactured and tested at the National High Magnetic Field Laboratory and on July 21, 2004 it was energized to 21.1 T. Commercial and unique homebuilt probes, along with a standard commercial NMR console have been installed and tested with many science applications to develop this spectrometer as a user facility. Solution NMR of membrane proteins with enhanced resolution, new pulse sequences for solid state NMR taking advantage of narrowed proton linewidths, and enhanced spatial resolution and contrast leading to improved animal imaging have been documented. In addition, it is demonstrated that spectroscopy of single site (17)O labeled macromolecules in a hydrated lipid bilayer environment can be recorded in a remarkably short period of time. (17)O spectra of aligned samples show the potential for using this data for orientational restraints and for characterizing unique details of cation binding properties to ion channels. The success of this NHMFL magnet illustrates the potential for using a similar magnet design as an outsert for high temperature superconducting insert coils to achieve an NMR magnet with a field >25 T.

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians.

BACKGROUND: Osteoporosis, mainly characterised by low bone mineral density (BMD), is a serious public health problem. The collagen type I alpha 1 (COL1A1) gene is a prominent candidate gene for osteoporosis. Here, we examined whether genetic variants at the COL1A1 gene can influence BMD variation. METHODS: BMD was measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females. We screened four single nucleotide polymorphisms (SNPs) at the COL1A1 gene: PCOL2 (-1997 G/T) in the promoter, Sp1 (1546 G/T) in the intron 1, Gly19Cys (3911 G/A) in exon 8, and Ala897Thr (13 773 G/A) in exon 45. Univariate and multivariate association approaches were used in the analyses. RESULTS: In multivariate analyses, we found a strong association between the PCOL2 SNP and BMD (p = 0.007 to 0.024) and a suggestive association between the Sp1 SNP and BMD (p = 0.023 to 0.048) in elderly Caucasian females. Interestingly, the interaction of these two SNPs was highly significantly associated with BMD variation (p = 0.001 to 0.003). The haplotype GG at the two SNPs had, on average, 2.7% higher BMD than non-carriers (p = 0.006 to 0.026). CONCLUSIONS: Our data suggested that the common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to BMD variation in elderly Caucasian females. Further studies are necessary to delineate the mechanisms underlying the effects of these common variants on BMD variation and to test their clinical relevance for general populations. In addition, our study highlighted the importance of multivariate analyses when multiple correlated phenotypes are under study.

A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27.

BACKGROUND: Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation. OBJECTIVE: To substantiate these previous findings and detect new genomic regions. METHODS: A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced approximately 8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method. RESULTS: The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12. CONCLUSIONS: Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.

Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.

Effects of grades and other loads on on-road emissions of hydrocarbons and carbon monoxide.

This project was developed to assess driving patterns that promote high emissions episodes, also known as emission excursions, particularly while driving on roads with grade. An instrumented vehicle was equipped to record driving conditions such as speed and grade, as well as measure emission rates of total hydrocarbons and carbon monoxide. Controlled runs with predetermined cruise speeds between 35 and 55 mph and accelerations less than 3.3 mph/second were conducted on flat terrain and on hills with grades ranging from 0 to 7%. The hills were located in metropolitan Los Angeles, both along freeways and arterial roads. For hydrocarbons, the increase in emissions was about 0.04 g/mile for each 1% grade increment. For carbon monoxide (CO), the increase was more dramatic: 3.0 g/mile for each 1% grade increment. For a fully occupied vehicle with four passengers on a 4.5% grade, emissions increased by 0.07 g/mile for hydrocarbons and 10.2 g/mile for CO. Air conditioning operation, at full setting, further increased emissions while driving on hills (4.5 and 6.7% grades) by 0.07 g/mile for hydrocarbons and 31.9 g/mile for CO.

Pasteurella anatipestifer as a cause of mortality in captive wild waterfowl.

An outbreak of Pasteurella anatipestifer infection in young wild waterfowl at the Niska Waterfowl Research Center resulted in losses of approximately 100 Blue and Snow Geese, one White-fronted Goose, five Mandarin Ducks, one Black Duck and one Wood Duck. Clinical signs included diarrhea, paralysis and tremors. Gross lesions were fibrin deposits on serosal surfaces, hemorrhages on the epicardium, consolidation of the lungs, cloudy or flaky deposits on the air sacs, and dark, swollen spleens. Microscopic lesions included fibrinous meningitis, pneumonitis, air saculitis and serositis. Swollen leg and foot joints were seen in some cases. Chloramphenicol treatment seemed to be of benefit in controlling the outbreak.

Studies on Salmonella from floor litter of 60 broiler chicken houses in Nova Scotia.

Fifteen floor litter samples were collected from each of 60 broiler chicken houses in Nova Scotia. Salmonella was recovered from 270 litter samples (30%) in 33 of 60 (55%) houses. All isolates were serotyped. Salmonella heidelberg and S. infantis were the most common of the 13 serotypes found. Isolates of selected serotypes were phage typed. Most isolates were susceptible to all common antimicrobial agents.

Pulmonary adenomatosis (jaagsiekte) of sheep in Canada.

Sheep pulmonary adenomatosis has recently been reported in Canada. The literature is briefly reviewed and an account of the present status of the disease in Canada is described.Sheep pulmonary adenomatosis was first diagnosed in Canada in December 1979 in a first generation descendent of sheep imported from Great Britain. In March 1980 two further cases of sheep pulmonary adenomatosis were diagnosed in a second flock. A total of 43 sheep involving eight flocks from five provinces have been observed from December, 1979 to May, 1981. The clinical signs and laboratory findings were similar to those described in sheep from other countries. It is estimated that 30% of Canadian flocks may contain sheep imported from Great Britain during the 1970's.