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Biomedical subjects

N Lane

Publications and source records attributed to N Lane.

At least 19 recordsLinked to original sources
PubMed2006

"Punk" rock can be bad for you: a case of surgical emphysema from a "punk" rocker's leather jacket.

Stab wounds to the thorax are seen in the emergency department (ED) and can be caused by a variety of mechanisms. This case highlights an unusual cause of injury: a leather jacket with spikes on the back of it. This type of jacket is often worn by "punks" as a fashion statement. We report that falling onto such a jacket may result in accidental thoracic injury leading to subcutaneous emphysema. A thorough clinical assessment is mandatory to exclude underlying lung injury or pneumothorax. In patients with subcutaneous emphysema and an otherwise normal chest radiograph, an in hospital observation period of 24 hours to check for any delayed complications is adequate if the patient remains clinically stable.

Adult↗
PubMed2006

Assessing the welfare of genetically altered mice.

In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

Animal Husbandry↗
PubMed2005

Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells.

Novel assay methods developed for the isolation and characterization of circulating tumor cells (CTC) of epithelial origin offer the potential of markers for the non-invasive gathering of clinical information relevant to the diagnosis, evolution and treatment of carcinoma. Of the numerous techniques currently used to analyze CTC, slide-based assays are perhaps the most common. While traditional combined immunocytochemical/brightfield microscopy systems continue to be the most frequently employed, fluorescence-based analysis is gaining in importance. This is partly because fluorescence microscopy analysis of slide-mounted CTC can provide simultaneously cytogenetic as well as morphologic and multiple phenotypic information. In particular, fluorescence microscopy analysis of slide-mounted CTC can accurately determine genetic changes at the chromosomal level in patients with recurrent disease. More importantly, by identifying genetic aberrations in CTC, it becomes possible to choose those patients most likely to benefit from a given treatment. The potential of this technique has already been demonstrated by employing fluorescence in situ hybridization (FISH) methods to measure expression of the HER2/neu gene in tissue from patients with breast carcinoma for the specific purpose of identifying those patients most likely to respond to Trastuzumab targeted therapy. Here, we review the major methodologies used in the preparation and analysis of the slide-based assays.

Carcinoma↗
PubMed2003

Incidence of nonvertebral fractures in relation to time on treatment and bone density in glucocorticoid-treated patients: a retrospective approach.

The effects of duration of treatment and bone mineral density (BMD) on nonvertebral fracture in 560 glucocorticoid users were examined by using baseline and retrospective data from 2 parallel studies assessing the efficacy and safety of alendronate therapy. Baseline spine and hip BMD were significantly (P < 0.01) lower with increased time spent receiving glucocorticoids. Forty-three patients (7.7%) had experienced at least 1 nonvertebral fracture after starting glucocorticoid treatment. The hazard function for nonvertebral fracture occurrence increased significantly (P < 0.01) with time spent receiving glucocorticoids: fracture incidence per 1,000 person-years on glucocorticoids was 18 (< 5 years), 31 (5-10 years), and 35 (> 10 years). Patients with a history of nonvertebral fractures after starting glucocorticoid treatment had significantly lower lumbar spine (P < 0.01) and hip (< 0.01) BMD value than those without fractures. This retrospective analysis suggests that a BMD measurement of spine and hip may identify risk for nonvertebral fractures in a heterogeneous population of glucocorticoid users.

Journal Article↗
PubMed2000

Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting.

The clustered organization of most imprinted genes in mammals suggests coordinated genetic and epigenetic control mechanisms. Comparisons between human and mouse will help in elucidating these mechanisms by identifying structural and functional similarities. Previously we reported on such a comparison in the central part of the mouse imprinting cluster on distal chromosome 7 with the homologous Beckwith-Wiedemann syndrome (BWS) gene cluster on human chromosome 11p15.5. Here we focus on the adjacent sequences of 0.5 Mb including the KCNQ1/Kcnq1 and CDKN1C/Cdkn1c genes, which are implicated in BWS, and on one of the proposed boundary regions of the imprinting cluster. As in the previously analysed central region, this part of the cluster exhibits a highly conserved arrangement and structure of genes. The most striking similarity is found in the 3' part of the KCNQ1/Kcnq1 genes in large stretches of mostly non-coding sequences. The conserved region includes the recently identified KCNQ1OT1/Kcnq1ot1 antisense transcripts, flanked by a strikingly conserved cluster of LINE/Line elements and a CpG island which we show to carry a maternal germline methylation imprint. This region is likely to be the proposed second imprinting centre (IC2) in the BWS cluster. We also identified several novel genes inside and outside the previously proposed boundaries of the imprinting cluster. One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain.

Alternative Splicing↗
PubMed2000

Active demethylation of the paternal genome in the mouse zygote.

DNA methylation is essential for the control of a number of biological mechanisms in mammals [1]. Mammalian development is accompanied by two major waves of genome-wide demethylation and remethylation: one during germ-cell development and the other after fertilisation [2] [3] [4] [5] [6] [7]. Most previous studies have suggested that the genome-wide demethylation observed after fertilisation occurs passively, that is, by the lack of maintenance methylation following DNA replication and cell division [6] [7], although one other study has reported that replication-independent demethylation may also occur during early embryogenesis [8]. Here, we report that genes that are highly methylated in sperm are rapidly demethylated in the zygote only hours after fertilisation, before the first round of DNA replication commences. By contrast, the oocyte-derived maternal alleles are unaffected by this reprogramming. They either remain methylated after fertilisation or become further methylated de novo. These results provide the first direct evidence for active demethylation of single-copy genes in the mammalian zygote and, moreover, reveal a striking asymmetry in epigenetic methylation reprogramming. Whereas paternally (sperm)-derived sequences are exposed to putative active demethylases in the oocyte cytoplasm, maternally (oocyte)-derived sequences are protected from this reaction. These results, whose generality is supported by findings of Mayer et al. [9], have important implications for the establishment of biparental genetic totipotency after fertilisation, the establishment and maintenance of genomic imprinting, and the reprogramming of somatic cells during cloning.

Actins↗
PubMed2000

Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia.

OBJECTIVE: Because there is controversy regarding the efficacy of acetaminophen in rheumatic diseases and because apparently safer nonsteroidal antiinflammatory drugs (NSAIDs) are being produced, we surveyed rheumatic disease patients about their preferences for these agents to determine the degree to which one type of therapeutic agent is preferred over the other. METHODS: In 1998, we surveyed by mailed questionnaire 1,799 patients with osteoarthritis (OA), rheumatoid arthritis, or fibromyalgia who were participating in a long-term outcome study. Patients who had taken acetaminophen rated the effectiveness of acetaminophen, compared its effectiveness with that of NSAIDs, and then rated their overall satisfaction with acetaminophen compared with NSAIDs when both effectiveness and side effects were considered. RESULTS: Two-thirds of study participants had taken acetaminophen. About 37% of patients who had taken acetaminophen found it to be moderately or very effective and about 63% indicated that it was not effective or was only slightly effective. One-fourth of the patients found acetaminophen and NSAIDs to be equally effective, but >60% found acetaminophen to be much less effective or somewhat less effective. About 12% preferred acetaminophen to NSAIDs. When both effectiveness and side effects were considered together, 25% of the patients had no preference, 60% preferred NSAIDs, and 14% preferred acetaminophen. CONCLUSION: There was a considerable and statistically significant preference for NSAIDs compared with acetaminophen among the 3 groups of rheumatic disease patients. Although this preference decreased slightly with age and was less pronounced in OA patients, the preference was noted among all categories of patients and was not altered by disease severity. If safety and cost are not issues, there would hardly ever be a reason to recommend acetaminophen over NSAIDs, since patients generally preferred NSAIDs and fewer than 14% preferred acetaminophen. If safety and costs are issues, then the recommendation of the American College Rheumatology that acetaminophen be tried first seems correct, since 38.2% found acetaminophen to be as effective or more effective than NSAIDs.

Acetaminophen↗
PubMed2000

[Effects of early estrogen replacement therapy on bone stability of ovariectomized rats. A biomechanical and radiologic study of the tibial plateau].

Postmenopausal osteoporosis leads to a significant increase in bone fragility. In this study we used the rat tibia plateau fracture model to investigate the efficiency of estrogen replacement therapy (ERT) to mitigate the post-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 animals underwent sham operation. The ovariectomized animals were either untreated (n = 35) or treated with estrogen injections (10 micrograms/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days post surgery. Before starting ERT and at 50 days post surgery, the trabecular structure of the right proximal tibial metaphysis of each animal was imaged non-invasively using high resolution X-ray topography. The animals were then sacrificed and the right knee from each animal was harvested and mounted into a servo-hydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administration was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham group, though this difference did not reach statistical significance. Across all groups, the failure load and stiffness were significantly correlated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.

Animals↗
PubMed2000

In vivo assessment of trabecular bone structure using fractal analysis of distal radius radiographs.

Our purpose in this study was (i) to measure trabecular bone structure using fractal analysis of distal radius radiographs in subjects with and without osteoporotic hip fractures, and (ii) to compare these measures with bone mineral density (BMD) as well as with measures of trabecular bone structure derived from high resolution magnetic resonance (MR) images. Distal radius radiographs were obtained using semi-industrial films (55 kVp, 400 mAs) in 30 postmenopausal patients, who had suffered osteoporotic hip fractures (74.8+/-8.2 years) in the last 24 months and 27 postmenopausal age-matched (74.6+/-6.6 yr) normal volunteers. Radiographs were digitized at 50 microm. A Fourier power spectrum-based fractal dimension (FD) characterizing the trabecular pattern was measured in a region of interest proximal to the joint line. The fractal dimension was calculated over two spatial frequency (f) ranges: FD1 was calculated over 0.5<log(f)<l.0, FD2 over the higher range 1.0<log(f)<1.5. Trabecular BMD in the radius was obtained using peripheral quantitative computed tomography (pQCT) (Stratec GmbH, Germany). In addition BMD of the proximal femur was determined using dual x-ray absorptiometry (DXA) (QDR 2000, Hologic, MA). In a subset of patients (16 controls and 18 with hip fractures), high resolution MR imaging of the distal radius (spatial resolution of 156 x 156 x 500 microm) was used to obtain measures analogous to bone histomorphometry. There were significant differences (p<0.05) between the fracture and nonfracture groups in the total femur BMD (13%), trabecular BMD in the distal radius (4%), and the fractal dimension in the radiographs (FD2) (3%). The correlations between FD2 and the total femur BMD as well as trabecular bone BMD in the distal radius were -0.48 (p<0.006) and -0.22 (p<0.33); respectively; FD1 increased with BMD and showed lower correlations. FD2 showed good correlations with App. Tb.N (-0.71) and App. Tb.Sp (0.69) (p<0.01), moderate correlation with App BV/TV (-0.53) (p<0.05), and no significant correlation with App. Tb.Th. The correlations between structural measures and FD1 showed the inverse trend and were typically lower. The odds ratios for a hip fracture were 2.44 for total femur BMD, 1.5 for trabecular BMD (radius), and 1.5 for FD2, respectively. In summary, the fractal measures derived from radiographs of the radius show differences between subjects with and without hip fractures, the predictive power of measures in the distal radius are comparable to radial trabecular BMD but lower than that of total hip BMD.

Aged↗
PubMed1999

Sources of career disadvantage in nursing. A study of NHS Wales.

Despite the numerical predominance of women in nursing there is a marked concentration of women, especially those working part-time, in the lower echelons of the profession. The paper presents survey data and interview material from a study of qualified nurses in NHS Wales. By controlling for differences in education and experience in nursing work, it was found that comparable groups of female nurses received unequal employment opportunities. Women with dependent children were primarily located in the lower nurse grades irrespective of their qualifications and experience. Much of this was associated with inflexible working practices, and the low status of part-time work. Occupational downgrading for female returners was also a significant barrier to career advancement. However, these problems were not recognised by management. Management failed to evaluate the mechanics of their human resource policies in terms which matter to many nurses, in particular with regard to the management of diversity.

Career Mobility↗
PubMed1997

Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy is established.

The majority of BALB/c mice immunized with the BCL1 lymphoma-derived idiotype (Id+) IgM and subsequently challenged with BCL1 tumor cells develop a state of tumor dormancy. The vast majority of dormant lymphoma cells are in cell cycle arrest, but there are also residual replicating cells. In the present studies, we attempted to define features of both the dormant lymphoma cells and the host that lead to escape from dormancy. Escape from dormancy occurs at a steady rate over a 2-year period, suggesting that it is a stochastic process. We found that, in the majority of mice, escape was due to the emergence of genetic variants that were no longer susceptible to the anti-Id-mediated induction of dormancy. Ten percent of these variants were Id-; the remainder were Id+ but could grow in the presence of anti-Id antibodies, suggesting that there were mutations in molecules involved in one or more mIg-mediated negative-signaling pathways. In two of five such escapees, alterations in either Syk, HS1, and/or Lyn were observed. In a small percentage of mice, a low titer of circulating anti-Id antibody before tumor challenge correlated with a subsequent, more rapid loss of dormancy.

Adaptor Proteins, Signal Transducing↗