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Biomedical subjects

J W Chow

Publications and source records attributed to J W Chow.

At least 73 records · Page 4Linked to original sources

Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation.

We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13-wk-old rats. We used this model to relate the kinetics of the bone-forming response, as measured by administration of fluorescent markers, to an in situ hybridization analysis of changes in mRNA for two matrix proteins (type I collagen and osteocalcin) and a growth factor implicated in the regulation of bone formation [insulin-like growth factor I (IGF-I). We found that increased fluorochrome labeling was accompanied by an increase in the proportion of trabecular bone surfaces on which transcripts for collagen type I and osteocalcin were detectable, from < 3 to 25% 72 h after loading. IGF-I expression on trabecular surfaces showed a slightly earlier increase. We also noted intense hybridization for IGF-I in osteocytes in the diaphyseal cortex and in metaphyseal trabeculae. This was observed only in loaded bones, within 6 h of loading, and became undetectable in trabecular osteocytes 48 h and cortical osteocytes 120 h after loading. This is the first identification of a specific mRNA species in osteocytes after mechanical stimulation. Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF-I, in the osteogenic response of bone to mechanical stimulation.

Animals↗

Epidemiologic perspectives on Enterobacter for the infection control professional.

Enterobacter species have emerged as important nosocomial pathogens. Common reservoirs for these organisms include wounds and the gastrointestinal, urinary, and respiratory tracts. Enterobacter bacteremia typically occurs in patients with long-standing underlying illnesses who received antimicrobial agents before their bacteremia. The wide use of broad-spectrum antibiotics has contributed to the increased prominence of Enterobacter infections. Enterobacter species have a propensity to emerge resistant to the antibiotic therapy administered. Plasmid analysis, restriction endonuclease analysis of total cellular DNA, pulsed-field electrophoresis, and ribotyping can be valuable in investigating the spread of antibiotic-resistant strains.

Anti-Bacterial Agents↗

Tn924, a chromosome-borne transposon encoding high-level gentamicin resistance in Enterococcus faecalis.

Enterococcus faecalis SF350 is a clinical isolate from Winnipeg, Canada, with high-level (MIC > 2,000 micrograms/ml) gentamicin resistance. The genetic determinant for gentamicin resistance was located on the chromosome of SF350 and could be mobilized by a coresident conjugative plasmid, pYN120. Genetic and physical analyses showed that the gentamicin resistance determinant was located on a 27-kb transposable element which was designated Tn924.

Chromosomes, Bacterial↗

Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance.

Enterococcus faecium strains resistant to ampicillin, high levels of gentamicin, and vancomycin but susceptible to teicoplanin (vanB class vancomycin resistance) were recovered from 37 patients during an outbreak involving a 250-bed university-affiliated hospital. Three isolates with vancomycin MICs ranging from 8 to 256 micrograms/ml all hybridized with a vanB probe. Restriction endonuclease analysis of chromosomal and plasmid DNA suggested that all isolates tested were derived from a single clone. Vancomycin resistance was shown to be transferable. Risk factors for acquiring the epidemic strain included proximity to another case patient (P, 0.0005) and exposure to a nurse who cared for another case patient (P, 0.007). Contamination of the environment by the epidemic strain occurred significantly more often when case patients had diarrhea (P, 0.001). Placing patients in private rooms and requiring the use of gowns as well as gloves by personnel controlled the outbreak. These findings suggest that multidrug-resistant E. faecium strains with transferable vanB class vancomycin resistance will emerge as important nosocomial pathogens. Because extensive environmental contamination may occur when affected patients develop diarrhea, barrier precautions, including the use of both gowns and gloves, should be implemented as soon as these pathogens are encountered.

Adult↗

Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation.

The capacity of bone to adapt its architecture in response to changing mechanical demands is well recognized. However, the mechanisms by which mechanical stimuli are translated into new bone formation are poorly understood. Prostaglandins (PGs) may play a role. We therefore tested the effect of indomethacin on the cancellous bone formation induced by mechanical stimulation in the 8th caudal vertebrae of adult rats. Rats were given indomethacin 3 h before loading, 3 h before loading and daily thereafter, 6 h after loading, or 6 h after loading and daily thereafter. The increase in bone formation caused by loading was suppressed by a single dose of indomethacin if given before but not after loading. Daily administration of indomethacin suppressed the mechanical response, even when started after loading. These results suggest that PGs are essential for the transduction of mechanical stimuli into bone formation, and also that there may be two distinct phases of PG dependency in the response of bone to mechanical loading: an early phase associated with the immediate loading period and a later phase associated with osteogenic interactions entrained by the early phase.

Animals↗

The rate of cancellous bone formation falls immediately after ovariectomy in the rat.

We have recently found that administration of oestradiol-17 beta (OE2) to rats stimulates trabecular bone formation. It is not known, however, whether oestrogen has a similar action on bone formation rate under physiological circumstances. Oestrogen is known to suppress bone resorption, and oestrogen-deficient states in the rat, as in humans, are associated with an increase in bone resorption that entrains an increase in bone formation. To see if the latter masks a relative reduction in bone formation, due to oestrogen deficiency, we measured bone formation very early after ovariectomy, before the resorption-induced increase in bone formation becomes established. To do this, rats were administered fluorochrome labels before and after ovariectomy, spaced at weekly intervals in the first, and 3-day intervals in the second experiment. In both experiments there was a decrease in indices of bone formation in the labelling interval immediately following ovariectomy such that, using the shorter fluorochrome intervals, the mineral apposition rate fell to 69%, the double-labelled surface to 45%, and the bone formation rate to 36% of sham-ovariectomized levels. The reduction was not sustained in the subsequent label intervals, presumably masked by the increase in bone formation attributable to increased resorption. These results suggest that if bone formation is assessed before this resorption-entrained increase in bone formation occurs, oestrogen deficiency is associated with a reduction in dynamic indices of bone formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Histomorphometric changes in the skeleton of postmenopausal women with low bone mineral density treated with percutaneous estradiol implants.

OBJECTIVE: To identify the effects of percutaneous estradiol (E2) implants on bone histology and bone mass of postmenopausal women with low bone mineral density. METHODS: Sixteen postmenopausal women with low bone mineral density were treated with 75-mg E2 implants. Each had iliac crest bone biopsies performed, following double-tetracycline labeling, before treatment and 1 year later. Dual energy x-ray absorptiometry of the lumbar spine and proximal hip was also performed before and after 1 year of therapy. Serum E2 and FSH were measured after 1 year. RESULTS: There were significant reductions in the osteoid volume, osteoid surface, eroded surface, and activation frequency following treatment. There was a statistically insignificant increase in the median bone volume from 11.3 to 15.8%. The median percentage increase in bone density at the lumbar spine was 14.4% and at the total hip 5.3%. The median post-treatment serum E2 level was 570 pmol/L. CONCLUSIONS: Estradiol implants reduce bone turnover in the iliac crest without significantly increasing trabecular bone volume after 1 year. The increases in bone density at the spine and hip may be explained by increased mineralization within the existing trabecular bone. However, the iliac crest may not represent the effect of estrogen at sites susceptible to osteoporotic fracture. If resorption is suppressed more than formation, then new bone would be deposited to account for the increase in bone density.

Aged↗

Is pneumonia really the old man's friend? Two-year prognosis after community-acquired pneumonia.

Is pneumonia "the old man's friend"--a terminal event for patients who will otherwise die soon of underlying chronic disease? If so, chronological age might influence treatment policy. We investigated the predictors of 2-year mortality after patients' admission to hospital for community-acquired pneumonia, and focused on the predictive value of age. In a prospective cohort study 141 consecutive patients were admitted to hospital with community-acquired pneumonia. Clinical, laboratory, and sociodemographic data were collected on admission. Comorbidity was categorised as mild, moderate, or severe by a physician based on the patient's medical history. Survival was assessed at 24 months after discharge. 22 (16%) patients died in hospital. Of the remaining 119, 38 (32%) died over the next 24 months. In a Cox model, 2-year mortality was independently related to severe comorbidity (relative risk [RR] = 9.4) or moderate comorbidity (RR = 3.1), and to haematocrit less than 35% (RR = 2.9) (all p < or = to 0.005). However, compared with patients aged 18-44 years, patients aged 45-64 (RR = 0.84), 65-74 (RR = 1.28), and 75-92 (RR = 1.99) were not significantly more likely to die during the 24 months after discharge (all p > or = to 0.2). Old age should not be a sole criterion for withholding aggressive treatment of community-acquired pneumonia.

Adolescent↗

Bone formation is not coupled to bone resorption in a site-specific manner in adult rats.

The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. It has been clearly shown that in adult man the coupling of formation and resorption involves a site-specific sequence of events, in which bone resorption is normally followed, at the same site, by bone formation. Whether the coupled processes of bone resorption and formation also occur at the same site in the rat is controversial. To elucidate the spatial relationship between bone formation and resorption in the rat, we compared the percentage of crenated and non-crenated cement lines with the percentage of crenated and non-crenated bone surfaces in the proximal tibia of adult rats aged 16 weeks to 2 years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16-week-old and 7-month-old rats exhibited a low percentage (7-11%) of crenated cement lines, which is opposite to the proportion (88%) we observed in human trabecular bone. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone (rat 1.1-1.4% vs. 5% in humans). In older (2 years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to 45%. These results imply that the major proportion of bone formation in the trabecular bone of growing rats occurs on non-resorbed surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Estrogen does not restore bone lost after ovariectomy in the rat.

We recently found that 17 beta-estradiol (E2) not only suppresses bone resorption but also stimulates bone formation in the cancellous bone of female rats. This raises the possibility that E2 treatment might restore the bone lost after ovariectomy in the rat. To test this, 13-week-old rats were ovariectomized (ox). After a further 13 weeks the animals were injected with E2 (4 mg or 40 micrograms/kg daily), human calcitonin (hCT) (3 IU/kg daily), (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP) (0.3 mg/kg twice per week), or a combination of E2 with hCT or AHPrBP, for 8 weeks. The bone volume at the tibial metaphysis of ox animals was approximately 40% of that of sham-operated controls at the end of the experiment. Although the bone volume of ox rats treated with E2 and/or hCT or AHPrBP was slightly higher than that of untreated ox rats, the increase was not significant. Neither E2 alone nor a combination of E2 with hCT or AHPrBP was associated with a higher bone volume than hCT or AHPrBP alone, suggesting no effect of E2 beyond that of inhibition of bone resorption. Histodynamic indices of bone formation were increased in untreated ox rats compared to controls but suppressed in E2-treated, hCT-treated, and AHPrBP-treated animals. These results emphasize the similar responses of rat and human bone, both of which not only show bone loss with estrogen deficiency, preventable by estrogen administration, but also show an inability of estrogen to restore bone lost as a result of estrogen deficiency.

Animals↗

Excision of the hamate for an unusual hand tumour.

A right-handed man with an enlarging bony swelling of his dominant hand developed symptoms of median and ulnar nerve compression. He underwent simple excision of the hamate and histology showed the lesion to be a benign chondroblastoma. At 2-year follow-up he was found to be doing a heavy manual job with no functional problems and there were no signs of recurrence of the tumour. To our knowledge this is the first reported case of a benign hand tumour treated by simple excision of the hamate.

Bone Neoplasms↗

Induction of bone formation in rat tail vertebrae by mechanical loading.

We have developed an experimental model in which pins, inserted into the seventh and ninth caudal vertebrae of 13-week-old rats, are used to load the eighth caudal vertebra in compression. Four groups of animals were used in the study: unpinned; animals with pins inserted, but non-loaded; animals loaded once, for 360 cycles at 0.5 Hz; and animals subjected to daily loading for 36 cycles at 0.5 Hz. Pins were immobilised by clamps when not undergoing loading. The animals were killed 9 days after pinning, and the eighth caudal vertebra was subjected to histomorphometric and histodynamic analysis. We found that vertebrae subjected to 36 daily loading cycles showed a 30-fold increase in bone formation compared to non-loaded controls. A single loading regime of 360 cycles was sufficient to increase bone formation 4-fold. Bone formation on trabecular surfaces was of lamellar rather than woven bone and was accompanied by a decrease in indices of bone resorption. Loaded vertebrae also showed substantial periosteal woven bone formation, although a minor degree of periosteal woven bone formation was also seen in one non-loaded pinned control vertebra. Our results suggest that in the rat, as in avian species, short loading regimes are capable of inducing bone formation. The model may assist an analysis of the interactions between bone resorption, bone formation and mechanical stimuli, and may enable identification of the molecular signals that mediate induction of lamellar bone formation on trabecular surfaces.

Animals↗

Molecular characterization of highly gentamicin-resistant Enterococcus faecalis isolates lacking high-level streptomycin resistance.

Antimicrobial susceptibilities and DNA contents were analyzed for six clinical isolates of Enterococcus faecalis that had high-level resistance to gentamicin (MIC > 2,000 micrograms/ml) but not streptomycin and were obtained from patients in diverse geographic areas. Contour-clamped homogeneous electric field electrophoresis of genomic DNA showed all isolates to be different strains. Gentamicin resistance was transferred from four isolates to plasmid-free enterococcal recipients in filter matings. Restriction enzyme analysis of transconjugants showed distinct gentamicin resistance plasmids. A probe specific for the gentamicin resistance determinant hybridized to the plasmids of four isolates and to the chromosomes of two isolates. These findings suggest that clonal dissemination is not responsible for the spread of these resistant strains, that resistance determinants occur on different plasmids as well as on the chromosome of E. faecalis, and that the genetic determinants of resistance are related.

DNA Restriction Enzymes↗

Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis.

A rabbit endocarditis model was utilized to evaluate the virulence conferred by the conjugative plasmid pAD1 with the following strains: Enterococcus faecalis plasmid-free FA2-2 and FA2-2 containing plasmids pAD1 (hemolysin and aggregation substance positive), pAM9058 (insertional inactivation of hemolysin), and pAM944 or pAM947 (insertional inactivation of aggregation substance). All isolates were similar in ability to produce endocarditis. Mean vegetation weight was greater in animals inoculated with strains that produced aggregation substance (P < 0.01). Mortality was significantly increased in animals given FA2-2 containing pAD1 compared with those given all other strains (P < 0.01). These results suggest that the combination of hemolysin and aggregation substance is associated with increased mortality and that vegetation weight is associated with production of aggregation substance in experimental E. faecalis endocarditis.

Animals↗

Mobilization of the penicillinase gene in Enterococcus faecalis.

Enterococcus faecalis SF4855 is a beta-lactamase-producing isolate resistant to high levels of gentamicin, with determinants for these resistances on the chromosome. SF4855 transferred both determinants into E. faecalis FA2-2 and UV202 at a frequency of 10(-9) in the presence of the MLS plasmid pYN120. beta-Lactamase and gentamicin resistance probes hybridized to three locations on the chromosome of FA2-2 transconjugants on contour-clamped homogeneous electric field electrophoresis. The study results suggest mobilization of the beta-lactamase determinant.

Chromosomes, Bacterial↗

Clonal spread of vancomycin-resistant Enterococcus faecium between patients in three hospitals in two states.

The DNAs of 3* vancomycin-resistant Enterococcus faecium isolates from five hospitals in three states were analyzed by contour-clamped homogeneous electric field electrophoresis and plasmid analysis. There were 22 strain types. One strain type was common to patients in three hospitals in two states. These results suggest the apparent intra- and interhospital spread of vancomycin-resistant E. faecium.

Bacterial Typing Techniques↗

Characterization of osteogenic response to mechanical stimulation in cancellous bone of rat caudal vertebrae.

We have recently developed an experimental model in which pins, inserted into the 7th and 9th caudal vertebrae of 13-wk-old rats, are used to load the 8th caudal vertebra in compression. We have now applied this model to assess the responsiveness of rat cancellous bone to mechanical stimulation. We found that daily exposure to loads that induce strains similar to those observed in bone during relatively gentle physical activity, for 30 cycles/day, increased the rate of lamellar bone formation on cancellous surfaces by up to 140-fold. Bone formation rate showed a highly significant (P < 0.0001) correlation with the number of days for which the bones were loaded and with the size of the load. A single loading episode of 300 cycles, representing a 10-min period of loading, increased bone formation to 24 times that in nonloaded controls. Indexes of bone resorption were essentially the inverse of the bone formation parameters. These experiments show that rat cancellous bone is exquisitely sensitive to mechanical stimulation and suggest that the mechanical environment is a major determinant of the physiological behavior of mammalian cancellous bone.

Animals↗

Cephalosporin therapeutics for intensive care infections.

Third generation cephalosporins are valuable agents in the ICU setting because of their broad spectrum of activity, in vitro potency against the Gram-negative bacilli commonly isolated in the ICU, and excellent penetration into most body sites. Multiresistant organisms may emerge as a result of widespread injudicious use of these agents, and this possibility is of special concern since these organisms may be associated with higher mortality rates. Combination therapy may be superior to monotherapy in severely ill patients with Gram-negative bacteremia. Double-beta lactam therapy has been efficacious in selected patients, although this regimen has several theoretical disadvantages. When third-generation cephalosporins are used for Gram-negative rod bacteremia in the ICU, combination therapy with an aminoglycoside should be considered.

Aminoglycosides↗