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Biomedical subjects

P J Ryan

Publications and source records attributed to P J Ryan.

At least 19 recordsLinked to original sources
PubMed2004

Bupropion as an aid to smoking cessation: a review of real-life effectiveness.

Clinical trials rigorously demonstrate the efficacy of new products and justify their marketing. However, it is only after use in real-life settings that the clinical value (effectiveness) of a new treatment is fully known. The purpose of this review was to summarise the effectiveness data for bupropion SR as an aid to smoking cessation. Available reports of effectiveness data for bupropion SR were obtained from the literature, presentations at smoking cessation meetings and from the manufacturer. Twelve sources of effectiveness data were found and included clinical practice trials, observational studies/surveys, motivational support programme results and employer-based cessation programme results. The 6-month point prevalence smoking cessation rates ranged from 25 to 49%. There is a growing body of evidence supporting the effectiveness of bupropion SR as an aid to smoking cessation. Real-life quit rates for bupropion SR are similar to those seen in the original clinical trial programme.

Bupropion↗
PubMed2004

Single photon emission computed tomography scanning in the diagnosis of knee pathology.

PURPOSE: To evaluate the role of single photon emission computed tomography (SPECT) bone scan for the diagnosis of knee lesions in routine clinical practice. METHODS: 40 consecutive case records were examined in patients who underwent a SPECT scan prior to knee arthroscopy in routine clinical practice. The accuracy of clinical examination, SPECT scan results, and arthroscopic findings (as the gold standard) in diagnosing knee lesions were compared. RESULTS: The sensitivity of SPECT scans in detecting medial meniscal, lateral meniscal, anterior cruciate ligament lesions, osteochondral defects, and chondromalacia patellae was 77%, 14%, 33%, 50%, and 74%, respectively. The specificities for the same structural lesions were high at 89%, 94%, 97%, 94%, and 69%, respectively. CONCLUSION: SPECT bone scan appears to be useful in the diagnosis of knee pathology in routine practice and in selecting patients for arthroscopy, especially most useful for the diagnosis of medial meniscal tears.

Arthroscopy↗
PubMed2001

Production of colony-stimulating factors and IL-5 by organs from three types of mice with inflammatory disease due to loss of the suppressor of cytokine signaling-1.

Organs from neonatal mice dying from IFN-gamma-dependent inflammatory disease initiated by loss of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) had a normal capacity to produce G-CSF in vitro but a reduced capacity to produce GM-CSF, most evident with the lung, and some reduction in the production of M-CSF by muscle tissue. In contrast, organs from mice lacking the genes for both SOCS-1 and IFN-gamma had a normal capacity to produce CSFs. Organs from young adult mice dying with polymyositis and myocarditis that lacked SOCS-1 but were heterozygous for IFN-gamma had a normal capacity to produce GM-CSF and M-CSF, but muscle tissue produced significantly increased amounts of G-CSF and IL-5 with IL-5 production also being elevated for the salivary gland, thymus, and heart. Loss of the IFN-gamma gene alone had no impact on organ production of these cytokines in vitro. In none of the inflammatory disease models was IL-3 production detected. The SOCS-1 protein appears to have no direct influence on the cellular production of these cytokines and the abnormalities observed either depend on the coaction of IFN-gamma, or more likely, are linked with the invasion and destruction of tissue by T lymphocytes, macrophages, eosinophils, and neutrophils. The ability of local organs to produce these proinflammatory cytokines could contribute to the development and progression of these inflammatory lesions.

Animals↗
PubMed2001

The multi-organ origin of interleukin-5 in the mouse.

Murine Ba/F3 cells were transfected with cDNA for the alpha-chain of the murine interleukin-5 (IL-5) receptor and cloned lines of these cells were able to proliferate in response to as little as 2.5 pg/ml of IL-5. The bioassay was demonstrated to be specific for IL-5 and was able to measure IL-5 produced in culture by organs from adult C57BL/6 and BALB/c mice. The highest levels of IL-5 were produced by lung tissue but thymus and bladder consistently produced IL-5 and more variable production was observed by the heart, spleen, muscle, bone shaft, uterus and testes. Bone marrow cells produced no detectable IL-5. Observed levels of production of IL-5 were similar when using organs from mice lacking high-affinity receptors for IL-5 and from nu/nu, RAG-1-/- and NOD/SCID mice lacking T lymphocytes. In inflammatory peritoneal exudates induced by the injection of casein plus bacteria, levels of induced IL-5 were higher if the mice lacked high-affinity receptors for IL-5. The data indicate that T lymphocytes are not the dominant cellular source of IL-5 in organ-conditioned media and that local IL-5 production can occur with a wide range of normal murine organs.

Animals↗
PubMed2001

Bone densitometry in the management of Colles' fractures: which site to measure?

This study assessed whether patients with Colles' fractures can be evaluated by measurement of peripheral bone mineral density (BMD) instead of the more established axial BMD technique. 205 consecutive patients who had sustained a recent Colles' fracture were invited to attend for BMD measurement at the lumbar spine, hip and forearm by dual energy X-ray absorptiometry (DXA) using a Hologic QDR4500C instrument. Hologic normal reference ranges were used for spine and ultradistal radius BMD, and the NHANES 111 reference range was used for the femoral neck. 158 patients attended, of whom only 61 had a T-score below -2.5 at one of the three measured sites (84 T<-2.0, 112 T<-1.5). 36 patients had bilateral forearm fractures and did not undergo a forearm measurement. After excluding these patients and using a T-score of -2.5 as a diagnostic threshold, a spine and hip measurement strategy missed 26% of osteoporotic patients and a forearm only strategy missed 33%. If a forearm strategy is adopted, with axial BMD performed only on those patients with an ultradistal radial T-score of <-1.5 and >-2.5, 27 further scans would be required and only four patients with T<-2.5 at the spine or hip would be undetected. Where axial BMD measurement is performed, this should be accompanied by forearm BMD measurement in some patients with Colles' fractures. A peripheral bone mineral densitometry strategy using forearm BMD alone will miss many individuals with osteoporosis. Therefore where forearm, and probably any peripheral scanning method, only is used for patient assessment there should be close liaison with an axial BMD centre with agreed joint protocols, as some patients should be advised to have an additional axial BMD measurement following their peripheral BMD measurement.

Aged↗
PubMed2000

The VT+ and VT- isoforms of the fibroblast growth factor receptor type 1 are differentially expressed in the presumptive mesoderm of Xenopus embryos and differ in their ability to mediate mesoderm formation.

Previously, we cloned a variant form of the type 1 fibroblast growth factor receptor (FGFR1), FGFR-VT-, from Xenopus embryos (Gillespie, L. L., Chen, G., and Paterno, G. D. (1995) J. Biol. Chem. 270, 22758-22763). This isoform differed from the reported FGFR1 sequence (FGFR-VT+) by a 2-amino acid deletion, Val(423)-Thr(424), in the juxtamembrane region. This deletion arises from the use of an alternate 5' splice donor site, and the activity of the VT+ and VT- forms of the FGFR1 was regulated by phosphorylation at this site. We have now investigated the expression pattern and function of these two isoforms in mesoderm formation in Xenopus embryos. Cells within the marginal zone are induced to form mesoderm during blastula stages. RNase protection analysis of blastula stage embryos revealed that the VT+ isoform was expressed throughout the embryo but that the VT- isoform was expressed almost exclusively in the marginal zone. The ratio of VT+:VT- transcripts in the marginal zone indicated that the VT+ form was predominant throughout blastula stages except for a brief interval, coinciding with the start of zygotic transcription, when a dramatic increase in VT- expression levels was detected. This increase could be mimicked in part by treatment of animal cap explants with FGF-2. Overexpression of the VT+ isoform in Xenopus embryos resulted in development of tadpoles with severe reductions in trunk and tail structures, while embryos overexpressing the VT- isoform developed normally. A standard mesoderm induction assay revealed that a 10-fold higher concentration of FGF-2 was required to reach 50% induction in VT+-overexpressing animal cap explants compared with those overexpressing the VT- isoform. Furthermore, little or no expression of the panmesodermal marker Brachyury (Xbra) was detected in VT+-overexpressing embryos, while VT--overexpressing embryos showed normal staining. This demonstrates that VT+ overexpression had a negative effect on mesoderm formation in vivo. These data are consistent with a model in which mesoderm formation in vivo is regulated, at least in part, by the relative expression levels of the VT+ and VT- isoforms.

Animals↗
PubMed2000

Intermittent oral disodium pamidronate in established osteoporosis: a 2 year double-masked placebo-controlled study of efficacy and safety.

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55-75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p < 0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p < 0.01) and total-body BMD for groups A and B (p < 0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p < 0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage.

Administration, Oral↗
PubMed2000

The long-term performance of DXA bone densitometers.

Long-term performance of a bone mass measuring device is an important criterion when considering the purchase of such equipment and has been regarded as an important feature of dual X-ray absorptiometry (DXA). The performance of a 6-year-old bone densitometer, the Lunar DPX alpha, which has undertaken 1500 scans annually over this period, was assessed. The short-term coefficient of variation calculated from 15 measurements with repositioning on a single day, using the Lunar aluminium phantom, was 0.242%. Long-term precision, also calculated by the coefficient of variation, was 0.548%. The manufacturer's quality control (QC) procedure was performed daily and allowed the machine to be used except on 15 occasions when bone density measurements could be acquired after rebooting. However, a 2.2% shift in phantom values occurred in July 1996 owing to a photomultiplier tube failure, but this did not produce a failure in the Lunar QC. The optical disc drive was replaced in July 1997. The machine failed to back up on six occasions over the last 2 years owing to software corruption and the acquired femur data were not saved on seven occasions owing to overloading of the memory buffer. In conclusion, expected hardware failure and minor software problems have occurred. We were concerned that the manufacturer's QC failed to detect a 2% shift in the phantom bone mineral density values and recommend regular measurements of the Lunar aluminum phantom in addition to the daily QC measurement of the tissue-equivalent block. We were nevertheless impressed by the long-term stability and reproducibility of the Lunar DPX alpha.

Absorptiometry, Photon↗
PubMed1999

Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.

We have identified and cloned a novel connective tissue growth factor-like (CTGF-L) cDNA from primary human osteoblast cells encoding a 250-amino acid single chain polypeptide. Murine CTGF-L cDNA, encoding a polypeptide of 251 amino acids, was obtained from a murine lung cDNA library. CTGF-L protein bears significant identity ( approximately 60%) to the CCN (CTGF, Cef10/Cyr61, Nov) family of proteins. CTGF-L is composed of three distinct domains, an insulin-like growth factor binding domain, a von Willebrand Factor type C motif, and a thrombospondin type I repeat. However, unlike CTGF, CTGF-L lacks the C-terminal domain implicated in dimerization and heparin binding. CTGF-L mRNA ( approximately 1.3 kilobases) is expressed in primary human osteoblasts, fibroblasts, ovary, testes, and heart, and a approximately 26-kDa protein is secreted from primary human osteoblasts and fibroblasts. In situ hybridization indicates high expression in osteoblasts forming bone, discrete alkaline phosphatase positive bone marrow cells, and chondrocytes. Specific binding of 125I-labeled insulin-like growth factors to CTGF-L was demonstrated by ligand Western blotting and cross-linking experiments. Recombinant human CTGF-L promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, recombinant human CTGF-L inhibits osteocalcin production in rat osteoblast-like Ros 17/2.8 cells. Taken together, these results suggest that CTGF-L may play an important role in modulating bone turnover.

Amino Acid Sequence↗
PubMed1998

Identification of phosphorylated proteins associated with the fibroblast growth factor receptor type I during early Xenopus development.

Signaling through the FGF receptor (FGFR) is required for mesoderm induction in Xenopus. Some of the downstream signaling molecules implicated in this developmental process include Ras, Raf and MAP kinase. In a previous report, we demonstrated that PLC gamma 1, Grb-2, SOS and Nck were associated with activated FGFR1s in a signaling complex in Xenopus blastulae. In addition, several unidentified phosphotyrosylproteins were present in the FGFR1 complex. Here we identify three of these proteins as Ras-GAP, the p85 of P13'K and SHP2, while demonstrating that c-Src and She were not associated with the FGFR1. Furthermore, we show that three additional phosphotyrosylproteins from the FGFR1 complex specifically bound to the adaptor molecule Nck.

Animals↗
PubMed1998

Orthopaedic manifestations of systemic disease.

Nuclear medicine studies can be initiated to detect or evaluate systemic diseases such as inflammatory arthritis or Paget's disease. This is usually because of the strengths of nuclear medicine studies such as high sensitivity, an ability to easily image the whole body, and typical diagnostic patterns of abnormalities. In other instances, a systemic disease may be incidentally suggested by a scintigram such as osteoporosis or hyperparathyroidism; or a focal abnormality such as a vascular necrosis may be detected that should indicate a systemic condition should be sought. Although most nuclear medicine studies have high sensitivity for disease, specificity is often less and, for a particular scan abnormality, several conditions may have to be considered. Familiarity with the varying patterns of abnormality associated with different disease is therefore vital to correct assessment.

Arthritis↗
PubMed1998

The impact of influenza and influenza-like illness on productivity and healthcare resource utilization in a working population.

Four hundred and eleven subjects who either reported to Occupational Health at onset of influenza or influenza-like illness (I/ILI) symptoms or on return to work completed questionnaires on entry to the study and after 28 days. On average they were incapacitated or confined to bed for 2.4 days, missing 2.8 days from work per episode of illness. On return to work, they reported reduced effectiveness and inability to resume normal activity until a mean 3.5 days after the onset of symptoms. Each participant reported a mean of 6.5 I/ILI symptoms. There was a positive correlation between the number of symptoms and bed days (r = 0.24) and missed work days (r = 0.18). There was a positive correlation between the number of healthcare contact and the number of reported symptoms (r = 0.23). A relatively high level of contact with general practitioners and pharmacists was observed and there was substantial use of both prescription and over-the-counter medication. In conclusion, the impact of I/ILI on productivity in a working population and the resultant cost to employers and employees may be considerable.

Adult↗
PubMed1998

A prospective comparison of clinical examination, MRI, bone SPECT, and arthroscopy to detect meniscal tears.

Recent studies have shown that SPECT bone scintigraphy is valuable to detect meniscal tears of the knee. This has not been formally assessed in a prospective study, and no substantive study has compared bone SPECT with other noninvasive diagnostic methods. One hundred consecutive patients referred to an orthopedic surgeon with undiagnosed knee pain were assessed by clinical examination, MRI, SPECT bone scintigraphy, and arthroscopy. The MRI and SPECT bone scan findings were reported blinded to other information. Using arthroscopy as a gold standard, both MRI and SPECT showed high diagnostic ability to detect meniscal tears, with respective sensitivity rate, specificity rates, and positive and negative predictive accuracies of 80%, 71%, 84%, and 71% for MRI and 84%, 80%, 88%, and 76% for SPECT. Some meniscal tears were detected by MRI alone (n = 5) or SPECT alone (n = 8). SPECT bone scintigraphy is a suitable alternative to MRI to detect meniscal tears. The comparable diagnostic ability of SPECT bone scintigraphy implies that it can be used successfully when MRI is unavailable or unsuitable.

Adult↗
PubMed1997

cDNA cloning of a novel, developmentally regulated immediate early gene activated by fibroblast growth factor and encoding a nuclear protein.

We have utilized the polymerase chain reaction (PCR)-based differential display methodology (Liang, P., and Pardee, A. B. (1992) Science 257, 967-969) to identify a novel transcript whose expression levels increased in Xenopus embryo explants during mesoderm induction by fibroblast growth factor. The PCR product was used to clone a 2.3-kilobase pair cDNA representing this transcript, which we have named er1 (early response 1). The er1 cDNA contained a single open reading frame predicted to encode a protein of 493 amino acid residues. A data base homology search revealed that the predicted ER1 amino acid sequence contains three regions of similarity to the rat and human proteins encoded by the metastasis-associated gene, mta1, and two regions of similarity to the Caenorhabditis elegans sequence that is similar to mta1. The fibroblast growth factor-induced increase in er1 steady-state levels was not dependent on de novo protein synthesis, demonstrating that er1 is an immediate-early gene. Northern blot analysis revealed a single 2.8-kilobase pair mRNA that was observed predominantly during the initial cleavage and blastula stages of Xenopus development, with little or no detectable mRNA during subsequent development. Quantitative PCR analysis of early developmental stages showed that er1 peaked during late blastula. Computer-assisted analysis of the predicted ER1 amino acid sequence revealed two putative nuclear localization signals, four highly acidic regions clustered at the N terminus and a proline-rich region located near the C terminus. Subcellular localization by immunocytochemistry revealed that the ER1 protein was targeted exclusively to the nucleus. Transactivation assays using various regions of ER1 fused to the DNA binding domain of GAL4 demonstrated that the N-terminal acidic region is a potent transactivator. These data suggest that ER1 may function as a transcription factor.

3T3 Cells↗
PubMed1997

Overview of role of BMD measurements in managing osteoporosis.

The advent of effective treatments and the opportunity to precisely and accurately measure bone mass have probably been the greatest advances in the field of osteoporosis in the last decade. Bone densitometry has become the most widespread noninvasive method for the detection of osteoporosis and to provide advice on risk of future fractures. It has achieved an unquestioned role in clinical decision making for the management of osteoporotic patients.

Age Factors↗
PubMed1997

Bone scintigraphy in metabolic bone disease.

The bone scan has well-recognized appearances in metabolic bone diseases, with its main clinical value found in focal conditions or the focal complications of disease. In clinical practice, the bone scan is most widely used to detect fractures in osteoporosis and pseudofractures in osteomalacia and to evaluate Paget's disease.

Bone Diseases, Metabolic↗