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Biomedical subjects

J W Chow

Publications and source records attributed to J W Chow.

At least 91 records · Page 5Linked to original sources

The anabolic action of 17 beta-estradiol (E2) on rat trabecular bone is suppressed by (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP).

We have previously found that high doses of 17 beta-estradiol (E2), similar to those seen in late pregnancy, stimulate bone formation in adult rats. In this communication we tested the effects of a combination of E2 and (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) on bone formation and bone volume in rat bone. E2 (4 mg/kg/day subcutaneously for 17 days) stimulated the bone formation rate to 6 times that of control rats. This was reduced by a single administration of AHPrBP (0.3 mg/kg subcutaneously) to 3 times control levels, and by similar daily injections of AHPrBP to levels not significantly different from those of untreated rats. Suppression of bone formation was effected predominantly through a reduction in the percentage of double-labelled surfaces, consistent with reduced osteoblast recruitment. We found only relatively minor effects of AHPrBP on the mineral apposition rate, suggesting that AHPrBP affected osteoblast function less than osteoblast recruitment. Suppression of histodynamic parameters of bone formation by AHPrBP was associated with suppression of the increase in bone volume otherwise induced by E2. The suppression by AHPrBP of the effect of E2 on bone formation contrasted with its lack of effect on other target tissues for E2, since AHPrBP did not affect the E2-induced changes in longitudinal bone growth or uterine weight. These results suggest that AHPrBP inhibits the anabolic effect of estrogen on rat trabecular bone.

Animals↗

The progesterone antagonist, RU486 does not affect basal or estrogen-stimulated cancellous bone formation in the rat.

Although it has been suggested that progesterone may have a role in preventing postmenopausal bone loss, a number of studies have shown that progesterone has no additive effect on estrogen therapy. We have recently found that high-dose estrogen stimulates bone formation in rats. The effect of progesterone on this anabolic action of estrogen has not been tested. We therefore investigated the role of progesterone in combination with endogenous or exogenous estrogen on bone formation in rats using RU486, which has been shown to be a potent progesterone antagonist without detectable agonist effects. Three-month-old Wistar female rats were treated for 17 days with RU486, and histomorphometric indices of bone formation were measured at the proximal tibial metaphysis after administration of double fluorochrome labels. Animals treated with RU486 (10 mg/kg) showed no change in either bone formation rate or double-labelled bone surfaces compared to vehicle-treated controls. Estrogen (17 beta-estradiol, 4 mg/kg) increased both indices by more than double compared with controls. RU486 did not affect the indices of increased bone formation in estrogen-treated rats. Estrogen also exhibited inhibition of longitudinal bone growth, while RU486 had no effect either in normal or estrogen-treated animals. These results show that the progesterone antagonist affects neither the stimulatory effect on formation nor the inhibitory effect on longitudinal bone growth by estrogen. These results suggest that progesterone does not play a significant role in either bone formation or bone growth in the rat.

Animals↗

Group A streptococcal meningitis.

Meningitis due to group A streptococci occurs uncommonly. We report two cases, one in a patient with otitis media and the other in a patient with bullous pemphigoid. Nineteen cases in the English-language literature from the past decade plus our two cases are reviewed. In 17 patients, an associated illness was present, most often otitis media or pharyngitis. When performed, gram staining of the cerebrospinal fluid and cultures of blood usually yielded organisms. Cerebrospinal fluid was acellular in two patients. Of 21 patients, 20 survived. Antibiotic therapy, which consisted of penicillin for most patients, was effective. Ceftriaxone may be an alternative agent. Neurologic sequelae occurred more often in children than in adults.

Aged↗

Molecular typing of ampicillin-resistant, non-beta-lactamase-producing Enterococcus faecium isolates from diverse geographic areas.

Molecular typing methods were compared by using 66 ampicillin-resistant, non-beta-lactamase-producing Enterococcus faecium clinical isolates from diverse geographic areas. Whole-plasmid analysis, restriction enzyme analysis of plasmid DNA with EcoRI and HindIII, and contour-clamped homogeneous electric field electrophoresis with digestion by SmaI and ApaI were performed on all isolates. Whole-plasmid analysis identified 47 different groups. Restriction enzyme analysis of plasmid DNA identified 50 groups when EcoRI was used and 51 groups when HindIII was used. Results with EcoRI and HindIII differed in 9 of 66 isolates. Grouping results with whole-plasmid analysis differed from results of restriction enzyme analysis of plasmid DNA (combining EcoRI and HindIII) in 20 of 66 isolates. Contour-clamped homogeneous electric field electrophoresis identified 46 groups when SmaI was used and 44 groups when ApaI was used. Results with SmaI and ApaI differed in 3 of 66 isolates. Grouping results with contour-clamped homogeneous electric field electrophoresis (combining SmaI and ApaI) differed from results of restriction enzyme analysis of plasmid DNA (combining EcoRI and HindIII) in 17 of 66 isolates. The combined use of whole-plasmid analysis, restriction enzyme analysis of plasmid DNA with two enzymes, and contour-clamped homogeneous electric field electrophoresis with two restriction enzymes should be considered when E. faecium is typed for epidemiologic investigation.

Ampicillin Resistance↗

17 beta-estradiol stimulates cancellous bone formation in female rats.

Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacological doses of estrogen increases bone formation in rats. Because such high doses of estrogen might induce bone formation through some mechanism other than the estrogen receptor, we have now assessed the effect of more physiological doses of 17 beta-estradiol (E2) on bone formation. Adult female rats (13 weeks and 6 months old) administered E2 (1, 4, 40, 400, and 4 mg/kg daily for 17-21 days) showed a dramatic increase (5- to 8-fold) in cancellous bone formation, attributable to a combination of an increase in the proportion of bone surface actively undertaking bone formation, and an increase in the rate of mineral apposition. Significant anabolism was induced in 6-month-old rats by doses as low as 4 micrograms/kg and in 13-week-old rats by 40 micrograms/kg. Corresponding increases in the proportion of trabecular surface covered by osteoblasts were also observed. Histomorphometric indices of bone resorption were suppressed by estrogen. Estrogen administration caused an increase in bone volume up to 35% over controls, over a 21-day period. Stimulation of bone formation by estrogen showed a similar pattern of dose-responsiveness to recognized physiological targets of E2: suppression of longitudinal growth and uterine growth. These results suggest that stimulation of cancellous bone formation is a physiological action of E2 in the rat.

Animals↗

Opposite effects of insulin-like growth factor-I on the formation of trabecular and cortical bone in adult female rats.

We have previously found that in intact adult female rats, 17 beta-estradiol (E2) stimulates trabecular bone formation, which can be detected by triple fluorochrome labeling within a few days of commencing E2 treatment. We have also observed that E2 stimulates trabecular bone formation in ovariectomised (Ovx) rats given 3-amino-1-hydroxypropylidene bisphosphonate (AHPrBP). This anabolic action of E2 is presumably mediated through the local release of growth factors, of which insulin-like growth factor-I (IGF-I) is a strong contender. To assess the role of IGF-I as mediator of the anabolic action of E2 on rat trabecular bone, we examined the effect of daily sc administration of IGF-I (200 micrograms/kg) for 17 days on trabecular bone formation at the proximal tibial metaphysis in experiments using the above two models. Intact animals received fluorochrome labels on days 1, 8, and 15 of IGF-I treatment, and Ovx animals received AHPrBP (0.3 mg/kg) on days 1, 8, and 15 and fluorochrome labels on days 8 and 15. Trabecular surfaces covered by first and second labels only (termed arrested surfaces), second and third labels only (induction surfaces), and all three labels (persisting surfaces) were assessed in intact animals; double labeled surfaces were assessed in Ovx animals. We found that IGF-I increased the longitudinal growth rate in both intact rats and Ovx animals given AHPrBP. However, to our surprise, we found that IGF-I inhibited trabecular bone formation in intact animals, reducing both arrested and persisting trabecular surfaces by approximately 50%. This was associated with a doubling of periosteal bone formation, as measured at the tibial diaphysis. In Ovx animals given AHPrBP, the AHPrBP markedly inhibited trabecular bone formation compared with that in Ovx controls, and IGF-I was without effect. We conclude that, in contrast to E2, IGF-I acts to increase the length and circumference of long bones and, perhaps through reactive mechanisms such as mechanical compensation, reduces rather than stimulates trabecular bone formation.

Animals↗

The anabolic effect of 17 beta-oestradiol on the trabecular bone of adult rats is suppressed by indomethacin.

We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17 beta-oestradiol (OE2)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE2 suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts.

Animals↗

Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy.

OBJECTIVES: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. DESIGN: Prospective, observational study of consecutive patients with Enterobacter bacteremia. SETTING: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. PATIENTS: A total of 129 adult patients were studied. MEASUREMENTS: The two main end points were emergence of resistance during antibiotic therapy and death. MAIN RESULTS: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. CONCLUSIONS: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.

Adolescent↗

Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes.

An imipenem-resistant strain, Enterobacter aerogenes EA-Z, was isolated from a blood culture. Outer membrane protein (OMP) profiles indicated the loss of a 40 kDa OMP, decreased expression of 42 and 44 kDa OMPs, and increased expression of a 50 kDa OMP in strain EA-Z when compared with imipenem-susceptible clinical isolates of E. aerogenes. The OMP profile of EA-Z was similar to that of strain EA-SI16, an imipenem-resistant E. aerogenes second-step mutant selected on imipenem-containing media. A single-step imipenem-resistant mutant, EA-SI8, had lost expression of only the 40 kDa OMP. No new beta-lactamase could be detected by isoelectric focusing, and no increase in imipenem hydrolysis was seen when EA-Z was compared with imipenem-sensitive controls, even in the presence of added zinc. These data suggest that the 40 kDa OMP of E. aerogenes might be required for the normal diffusion of imipenem across the outer membrane.

Bacteremia↗

Method for auditing turnround time in histopathology related to user requirements.

Histopathology audit schemes have concentrated on the accuracy of diagnosis or the standard of technical work. The most appropriate measure of specimen report time for histopathology was assessed. The simplest method is to calculate the mean or median number of days from receipt of specimens to issue of report, but this takes no account of clinical practice. An alternative approach is to compare the laboratory's performance with the clinicians' requirements. Clinicians were invited to complete a questionnaire specifying the reporting times they required subdivided by tissue type, clinical suspicion of malignancy, and bed occupancy of the patient. The questionnaire showed that there were distinct differences in clinicians' requirements. The turnround time for each category of specimen was calculated and expressed in three ways. The traditional method of quoting a median value showed very few differences among the categories. A comparison of the department's performance with the clinicians' requirements, using an arbitrary cut-off point of satisfying at least 80% of the clinicians' most stringent requirements or an achievement index, however, provided useful information for refining laboratory priorities.

Consumer Behavior↗

Endemic and atypical Kaposi's sarcoma in Africa--histopathological aspects.

Atypical HIV-associated and endemic Kaposi's sarcoma (KS) differ in their clinical presentation and behaviour. To assess the possible histological differences, a detailed review of 32 cases of atypical KS and 170 cases of endemic KS from sub-Saharan Africa was undertaken. Both forms of KS had similar histological appearances, and evolved through a chronological sequence of patch, plaque and nodule. There was an increase in the proportion of early patch and plaque lesions in cutaneous and mucosal atypical KS (54%) compared with endemic KS (23%). However, nodular lesions were still seen in atypical KS, and formed 56% of the total cases. In addition, atypical KS tended to have more small blood vessels and a lesser degree of inflammatory infiltrate. However, within each of the three stages of the disease, it was not possible to distinguish between the HIV- and non-HIV-related forms.

Adolescent↗

Staphylococcus aureus nasal carriage in hemodialysis patients. Its role in infection and approaches to prophylaxis.

Staphylococcus aureus infections remain a major cause of morbidity in hemodialysis patients. Chronic dialysis patients are more prone to staphylococcal infections because of their decreased immunity, increased skin colonization by staphylococci, and the multiple needle punctures required for dialysis. The source of the staphylococci is the anterior nares. Elimination of staphylococcal nasal carriage results in a significantly lower infection rate. Selected clinical studies of topical and oral therapy for eradication of staphylococcal nasal carriage are reviewed. Rifampin has been the most consistently efficacious agent, although emergence of resistance is a potential problem. Trials utilizing newer topical and oral agents for prophylactic eradication of S aureus from the nose are indicated. Promising antibiotics include topical mupirocin, the oral quinolones, and clindamycin.

Anti-Bacterial Agents↗

In vitro activity of sparfloxacin and clinafloxacin against multidrug-resistant enterococci.

We evaluated the in vitro susceptibility of 140 clinical enterococcal isolates to the quinolones sparfloxacin and clinafloxacin. Isolates included Enterococcus faecalis (107), Enterococcus faecium (29), Enterococcus raffinosus (3), and one Enterococcus gallinarum. There were 111 isolates that showed high-level [minimum inhibitory concentrations (MICs) > or = 2000 micrograms/ml] resistance to gentamicin and were resistant to high levels of all other aminoglycosides; five isolates produced beta-lactamase; 21 isolates were resistant (MIC > or = 16 micrograms/ml) to ampicillin and were not beta-lactamase producers; and 13 strains were resistant (MIC > or = 32 micrograms/ml) to vancomycin. Most strains were susceptible to low concentrations of sparfloxacin and clinafloxacin, with MIC90S of 0.6 microgram/ml and 0.5 micrograms/ml, respectively. There were no inoculum effects. Time-kill experiments were performed with 22 strains; using 2 x MIC at 24 h, a > or = 2 log10 reduction in growth was observed with sparfloxacin and clinafloxacin for 14 and 17 strains, respectively. Time-kill synergism experiments were performed with 15 strains lacking high-level aminoglycoside resistance. In vitro bacterial synergism with the combination of sparfloxacin or clinafloxacin with streptomycin or gentamicin was observed for five and 12 isolates, respectively. The bactericidal activity of sparfloxacin and clinafloxacin suggest that these antibiotics may prove useful for therapy of multidrug resistant enterococci.

Anti-Infective Agents↗

Synergy assessed by checkerboard. A critical analysis.

The checkerboard dilution test is widely used for evaluation of in vitro synergy for multiple drugs, although problems in performance, standardization, and interpretation have been noted. A major problem inherent in this commonly used method is the use of twofold dilutions for the antibiotic concentrations. We evaluated an alternative method proposed by Horrevorts and colleagues that preserved the twofold dilution scheme. Giant checkerboards were constructed from a series of component checkerboards using rifampin and minocycline against Staphylococcus aureus. We found that this method improved the stability of the fractional inhibitory concentration (FIC) indices, but required substantially more labor and generated other problems. FIC interpretation and calculation remained compromised by the twofold dilution scheme. We have analyzed the theoretical basis of the checkerboard and its FIC calculation and conclude that the twofold dilution with its exponential increase in dilutions makes this method of synergy evaluation inherently unstable. The principle of examining growth at multiple dilutions of combined antibiotics is valid for assessment of synergy, but newer methods need to be devised.

Drug Synergism↗