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Biomedical subjects

C Poon

Publications and source records attributed to C Poon.

14 recordsLinked to original sources

Factors affecting knee cartilage volume in healthy men.

OBJECTIVES: To understand the factors that influence joint cartilage in health and disease as they are important for the prevention and management of osteoarthritis. METHODS: We conducted a cross-sectional study to determine factors influencing knee cartilage volume in 45 males aged (mean+/-S.D.) 52.5+/-13.2 yr. RESULTS: Total and medial tibial volumes were inversely associated with age, body mass index (BMI) and amount of physical activity and positively associated with total bone content. BMI explained the largest amount of the variation in tibial cartilage volume (18.7%). There were similar findings at the lateral tibial cartilage, but for age and total bone content this did not reach statistical significance. There was a positive association with serum testosterone at all tibial cartilage sites, but this only reached statistical significance for medial tibial cartilage, where serum testosterone explained up to 8% of the variation in cartilage volume. CONCLUSIONS: Modifiable risk factors of osteoarthritis also appear to be significant determinants of tibial cartilage volume. Serum testosterone may provide one possible explanation for gender differences in tibial cartilage volume and prevalence of tibiofemoral osteoarthritis. The proposed link between osteoarthritis and knee cartilage volume and the effect of testosterone will need to be confirmed in longitudinal studies.

Adult↗

Overexpression of macrophage colony-stimulating factor receptor on microglial cells induces an inflammatory response.

Microglia are important in the inflammatory response in Alzheimer's disease (AD). We showed previously that macrophage colony-stimulating factor receptor (M-CSFR), encoded by the c-fms protooncogene, is overexpressed on microglia surrounding amyloid beta (Abeta) deposits in the APP(V717F) mouse model for AD. The M-CSFR is also increased on microglia after experimental brain injury and in AD. To determine the relevance of these findings, we transiently expressed M-CSFR on murine BV-2 and human SV-A3 microglial cell lines using an SV40-promoted c-fms construct. M-CSFR overexpression resulted in microglial proliferation and increased expression of inducible nitric-oxide synthase, the proinflammatory cytokines interleukin-1alpha, macrophage inflammatory protein 1-alpha, and interleukin-6 and of macrophage colony-stimulating factor (M-CSF) itself. Antibody neutralization of M-CSF showed that the M-CSFR-induced proinflammatory response was dependent on M-CSF in the culture media. By using a co-culture of c-fms-transfected murine microglia and rat organotypic hippocampal slices and a species-specific real time reverse transcriptase-polymerase chain reaction assay and enzyme-linked immunosorbent assay, we showed that M-CSFR overexpression on exogenous microglia induced expression of interleukin-1alpha by the organotypic culture. These results show that increased M-CSFR expression induces microglial proliferation, cytokine expression, and a paracrine inflammatory response, suggesting that in APP(V717F) mice increased M-CSFR on microglia could be an important factor in Abeta-induced inflammatory response.

Amidohydrolases↗

DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals.

DNA methyltransferase I (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis and after birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP system to produce conditional mutants that lack Dnmt1 in neuroblasts of embryonic day 12 embryos or in postmitotic neurons of the postnatal animal. Conditional deletion of the Dnmt1 gene resulted in rapid depletion of Dnmt1 proteins, indicating that the enzyme in postmitotic neurons turns over quickly. Dnmt1 deficiency in postmitotic neurons neither affected levels of global DNA methylation nor influenced cell survival during postnatal life. In contrast, Dnmt1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells. Whereas mutant embryos carrying 95% hypomethylated cells in the brain died immediately after birth because of respiratory distress, mosaic animals with 30% hypomethylated CNS cells were viable into adulthood. However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages.

Animals↗

Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study.

Osteoporosis in men is an emerging public health problem. As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women, we conducted a prospective study of this treatment in men with primary osteoporosis. Our study was a 2-yr, randomized, double masked, double placebo-controlled trial of calcitriol (0.25 microg twice daily) or calcium (500 mg twice daily) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture. Thirty-three men (85%) completed the study. There were no differences in baseline characteristics. Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups. Serum osteocalcin decreased in both groups by 30% (P < 0.05), whereas urine N-telopeptide cross-links decreased only in the calcium group by 30% (P < 0.05). After 2 yr, fractional calcium absorption increased by 34% (P < 0.01) in the calcitriol group. Nineteen incident fragility fractures occurred (14 vertebral and 5 nonvertebral) in 7 men. Over 2 yr, the number of men with vertebral fractures (6 vs. 1; P = 0.097) was similar in both groups. In conclusion, the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men.

Adult↗

A Porphyromonas gingivalis genetic locus encoding a heme transport system.

Porphyromonas gingivalis has been implicated in the onset and progression of periodontitis and the availability of hemin for in vitro growth has been associated with virulence of the bacterium in animal models. We report here the cloning and sequence analysis of a P. gingivalis TonB-linked outer membrane receptor gene tlr. This gene was previously identified as a TonB-linked adhesin gene tla and shown to be essential for growth at low concentrations of hemin. The tlr gene is immediately downstream of four open reading frames (htrABCD) that encode a putative ATP binding cassette transport system with sequence similarlity to heme transport systems of other bacteria. Analysis of P. gingivalis W50 mRNA revealed that the htrABCD genes are cotranscribed similar to hemin transport genes of other bacteria.

ATP-Binding Cassette Transporters↗

Placebo-controlled trial assessing the use of oral midazolam as a premedication to conscious sedation for pediatric endoscopy.

BACKGROUND: This study was performed to evaluate the effect of midazolam, as premedication before intravenous conscious sedation, on preprocedural, procedural, and post-procedural patient comfort and anxiety in children undergoing endoscopy. METHODS: A placebo-controlled, double-blind, randomized study was conducted in 123 children (age 7.75 +/- 4.46 years, 56% male) using oral midazolam (0.5 mg/kg, maximum 20 mg) as a premedication before insertion of an intravenous access device (i.v.) and upper endoscopy. Patients were evaluated with regard to changes in vital signs, level of sedation during i.v. placement, level of pre- and post-procedure conscious sedation, ease of separation from parents, ease and duration of procedure, recovery time, and amnesia to objects shown before i.v. placement and immediately before the start of the procedure. RESULTS: A significant difference was noted in the study group for the following parameters: level of sedation for i.v. placement (p < 0.0001), pre-procedural sedation (p < 0.001), ease of i.v. insertion (p < 0.003), ease of separation from parents (p = 0.022), and ease of the nursing personnel's ability to monitor the patient during the procedure (p = 0.0012). The patient's amnesia to an object shown immediately before beginning the endoscopy was increased (p < 0.001). Patients and parents were also more satisfied with the procedure process (p < 0.05). No significant difference was noted with regard to the length or performance of the procedure or recovery time or in the dose of i.v. medication required for successful completion of the endoscopy. CONCLUSION: Oral midazolam is an effective and safe premedication for children undergoing upper endoscopy and should be used in all anxious children and in patients previously judged to be difficult to sedate.

Administration, Oral↗

The prognostic value of thyrotropin receptor antibody measurement in the early stages of treatment of Graves' disease with antithyroid drugs.

In most trials, at least 50% of patients with Graves' disease treated with antithyroid drugs (ATD) relapse after achieving euthyroidism. At present, there are no definitive prognostic parameters available early in treatment to indicate those likely to achieve long-term remission. Because thyrotropin receptor antibodies (TRAb) are specific for Graves' disease, the possibility that their rate of change early in treatment (0 to 6 months) might be such an indicator was explored. TRAb were measured both as thyrotropin binding inhibitory immunoglobulins (TBII) and as thyroid-stimulating antibodies (TSAb) in 85 patients with untreated Graves' disease at 6-month intervals throughout their ATD treatment. The patients in the study were treated for a minimum period of 12 months and were categorized retrospectively into two groups depending on whether or not they remained in remission after ATD treatment. Remission was deemed as reached in patients who remained euthyroid for a minimum period of 15 months after cessation of ATD. The mean initial TBII and TSAb values in the nonremission group were significantly higher than in the remission group (p < 0.001 for both parameters). The rates of fall in mean TBII levels were similar for each group in the first 6 months of treatment, but while they continued to fall in the remission group over the next 6 to 12 months, mean values for the nonremission group plateaued and failed to fall to control levels within that period. These results indicate that changes in TRAb levels, measured either as TBII or TSAb, occur more rapidly in the second 6 months of treatment in patients who ultimately achieve remission than those who do not. If TBII fall to control levels by 12 months, the patient has at least a 70% chance of ultimately achieving remission with ATD treatment alone.

Adult↗

Studies of the surgical scrub.

BACKGROUND: To evaluate the effectiveness of various scrub techniques in reducing bacterial skin flora, the present study was developed in three stages. METHODS: Each stage involved fingertip bacterial colony counts measured before, immediately after and 30 min after a variety of handwashing techniques using 10% povidone iodine solution. The first compared 1, 2 or 3 non-timed washes from fingertips to elbows in 10 volunteers. The second compared two volunteers scrubbing for equal durations with or without friction rubbing, while the third involved 15 volunteers who each scrubbed for different time intervals. RESULTS: The first stage showed that a single wash episode failed to provide lasting bacterial colony count reductions on fingertip cultures. The second showed that enduring colony count reductions occur whether friction rubbing of the hands was used or not, and the third showed that a 30 s wash was as effective as washing for longer periods in reducing fingertip flora. CONCLUSIONS: These findings suggest that prolonged vigorous pre-operative scrubbing is unnecessary, although more than a cursory wash is required to produce lasting fingertip antisepsis.

Anti-Infective Agents, Local↗

A placebo-controlled trial using intravenous atropine as an adjunct to conscious sedation in pediatric esophagogastroduodenoscopy.

BACKGROUND: The usefulness of intravenous atropine as an adjunct to conscious sedation in pediatric esophagogastroduodenoscopy remains an unresolved issue. METHODS: This prospective, double-blind, randomized study examined 101 patients, who were randomized to receive either intravenous atropine 0.02 mg/kg (maximum 0.4 mg) or a placebo of normal saline solution prior to the procedure. RESULTS: The mean maximum heart rate during the procedure and the percentage of time that the heart rate was more than 1 standard deviation above mean for age was significantly greater in the atropine group as compared to the placebo group (p < 0.0005). There was no significant difference between groups in the amount of secretions noted, gastric motility, retching or vomiting, facial flushing, or dysphoria. There were no causes of significant bradycardia or hypotension in either group. There was a significant number of patients greater than 5 years of age and receiving meperidine and atropine (as compared with meperidine and placebo) whose arterial oxygen saturation dropped below 90% during the procedure (p = 0.0485). CONCLUSIONS: We found that the use of atropine when used as an adjunct to conscious sedation in children undergoing upper endoscopy did not increase the safety of the procedure or provide significant benefits. We do not recommend the routine use of atropine for upper endoscopy in pediatric patients.

Adjuvants, Anesthesia↗

Specific effects of radioiodine treatment on TSAb and TBAb levels in patients with Graves' disease.

Radioactive iodine (RAI)-induced changes in the levels of antibodies to the thyroid-stimulating hormone (TSH) receptor (TRAb) in patients undergoing treatment for autoimmune thyroid disease have been well documented. Previous studies have reported effects on the overall level of the antibodies present, TSH-binding inhibitory immunoglobulins (TBII), without detailed studies of specific effects on the levels of thyroid-stimulating (TSAb) or thyroid-blocking antibodies (TBAb). More detailed studies have been reported only in individual cases. In this study, the values of TSAb, TBAb, and TBII were measured longitudinally in 33 patients (27 females and 6 males) who received RAI. The bioassays for TSAb and TBAb were performed in JPO9 cells. Following RAI, there were significant and immediate effects on the values of TBII in 70% of patients. TBII levels fell in 7 patients (20%) (Group 1), rose in 16 patients (48%) (Group 2) or remained unchanged but elevated in 10 patients (32%) (Group 3). In the Group 1 patients, only TSAb were detectable and none of these patients became hypothyroid after treatment. In the 16 patients in Group 2, increases in TBII were attributable to specific increases in TSAb in 7 (44%), in TBAb in 3 (19%), and in both TSAb and TBAb in 3 (19%). There were 3 patients (19%) in this group in whom there was no detectable TSAb or TBAb activity despite the increase in TBII. Six patients from this group became hypothyroid within 6 months of RAI treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗