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Endocrinology, Diabetes & Metabolism... 2016Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of...
UNLABELLED
Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5-14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.
LEARNING POINTS
Girls with primary and secondary gonadal failure require assistance with pubertal induction.Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.
PubMed: 26843960
DOI: 10.1530/EDM-15-0096 -
British Journal of Pharmacology Nov 19931. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and...
1. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe 140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor, indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of indomethacin and atenolol were additive: their combination abolished responses to bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5 micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL-8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the dose of antiserum to TNF alpha or giving a combination of antisera to IL-1 beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms). 7. These data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram). The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram) suggests that the release of hyperalgesic cytokines can be initiated independently of bradykinin BK2 receptors.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atenolol; Bradykinin; Carrageenan; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Hyperalgesia; Indomethacin; Inflammation; Lipopolysaccharides; Male; Rats; Rats, Wistar; Time Factors
PubMed: 8298813
DOI: 10.1111/j.1476-5381.1993.tb13946.x -
Antimicrobial Agents and Chemotherapy Jan 1988Tigemonam is an orally administered monobactam. At less than or equal to 1 microgram/ml it inhibited the majority of strains of Escherichia coli, Klebsiella spp.,... (Comparative Study)
Comparative Study
Tigemonam is an orally administered monobactam. At less than or equal to 1 microgram/ml it inhibited the majority of strains of Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Citrobacter diversus, Proteus spp., Providencia spp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Serratia marcescens, and Yersinia enterocolitica. At less than or equal to 0.25 microgram/ml it inhibited Haemophilus spp., Neisseria spp., and Branhamella catarrhalis. It did not inhibit Pseudomonas spp. or Acinetobacter spp. Tigemonam was more active than cephalexin and amoxicillin-clavulanate and inhibited many members of the family Enterobacteriaceae resistant to trimethoprim-sulfamethoxazole and gentamicin. Some Enterobacter cloacae and Citrobacter freundii strains resistant to aminothiazole iminomethoxy cephalosporins and aztreonam were resistant to tigemonam. The MIC for 90% of hemolytic streptococci of groups A, B, and C and for Streptococcus pneumoniae was 16 micrograms/ml, but the MIC for 90% of enterococci, Listeria spp., Bacteroides spp., and viridans group streptococci was greater than 64 micrograms/ml. Tigemonam was not hydrolyzed by the common plasmid beta-lactamases such as TEM-1 and SHV-1 or by the chromosomal beta-lactamases of Enterobacter, Morganella, Pseudomonas, and Bacteroides spp. Tigemonam inhibited beta-lactamases of E. cloacae and Pseudomonas aeruginosa but did not induce beta-lactamases. The growth medium had a minimal effect on the in vitro activity of tigemonam, and there was a close agreement between the MICs and MBCs.
Topics: Administration, Oral; Anti-Bacterial Agents; Aztreonam; Culture Media; Escherichia coli; Gram-Negative Aerobic Bacteria; Humans; Monobactams; Mutation; beta-Lactamases
PubMed: 3279906
DOI: 10.1128/AAC.32.1.84 -
Blood Jan 1987Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and...
Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and leukocytes, respectively. It has been well documented that contact of blood with synthetic surfaces causes platelet activation. In this report, we explore mechanisms of the activation of neutrophils during simulated in vitro extracorporeal circulation and document the release of neutrophil lactoferrin and elastase during clinical cardiopulmonary bypass (CCB). Inhibition in the simulated circuit by prostaglandin E1 (PGE1) and lidocaine suggests different mechanisms for release of neutrophil-specific proteins. During CCB with a bubble oxygenator it was observed that platelet counts fell to 42% +/- 2% of baseline. In addition, beta-thromboglobulin antigen (beta TG), a platelet-specific, alpha-granule protein marker reflecting the release reaction, increased from 0.15 +/- 0.05 to 0.84 +/- 0.11 microgram/mL. Neutrophil counts decreased to 67% +/- 7% of prebypass levels but then gradually rose as bypass continued. Both lactoferrin, a neutrophil-specific granule marker, and neutrophil elastase, an azurophilic granule marker, increased in plasma threefold to 1.66 +/- 0.33 micrograms/mL and 1.65 +/- 0.68 microgram/mL, respectively, just before bypass was stopped. When fresh heparinized human blood was recirculated within an extracorporeal membrane oxygenator bypass circuit for 120 minutes, plasma beta-TG rose to 5.13 micrograms/mL, lactoferrin increased from 0.13 +/- 0.04 to 1.62 +/- 0.22 micrograms/mL, and neutrophil elastase rose from 0.05 +/- 0.02 to 1.86 +/- 0.41 micrograms/mL. At 120 minutes, lidocaine (100 mumol/L), which inhibits neutrophil activation, delayed release of lactoferrin (1.33 +/- 0.26 micrograms/mL) and markedly inhibited release of elastase (0.24 +/- 0.05 microgram/mL) but did not inhibit release of beta-TG antigen (5.66 micrograms/mL at 120 minutes). PGE1 (0.3 mumol/L) inhibited significantly the release of beta-TG (0.31 microgram/mL) and elastase (0.52 +/- 0.11 microgram/mL) and attenuated the release of lactoferrin (1.57 +/- 0.45 micrograms/mL).
Topics: Alprostadil; Cardiopulmonary Bypass; Cytoplasmic Granules; Exocytosis; Extracorporeal Circulation; Humans; Lactoferrin; Leukocyte Count; Lidocaine; Neutrophils; Pancreatic Elastase; Platelet Count; Secretory Rate; beta-Thromboglobulin
PubMed: 2947645
DOI: No ID Found -
Industrial Health 1994Blood and urine samples from cloisonne ware workers were assayed for Pb, Cr, Cd, Mn, Sb, Co and Cu for biological monitoring. Mean blood Pb levels were 47.8 +/- 27.3...
Blood and urine samples from cloisonne ware workers were assayed for Pb, Cr, Cd, Mn, Sb, Co and Cu for biological monitoring. Mean blood Pb levels were 47.8 +/- 27.3 micrograms/dl (111-13.3 micrograms/dl) for 49 cloisonne glaze workers, and 0.97 +/- 0.47 microgram/dl (2.4-0.6 microgram/dl) for 62 normal subjects. There was a distinct difference between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. There was a distinct difference in mean urinary Pb level between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. The correlation coefficient, r, between blood Pb and Cd levels was 0.631 (p < 0.01) for 132 subjects consisting of cloisonne ware workers and normal subjects. r between blood Pb and blood Cr levels was 0.501 (p < 0.01), and that between blood and urinary Pb levels, 0.794 (p < 0.01). The above assays showed that glaze workers at cloisonne plants suffer severe exposure to lead and slight exposure to Cd and Cr.
Topics: Antimony; Cadmium; Ceramics; Chromium; Cobalt; Copper; Humans; Japan; Lead; Manganese; Metals; Occupational Exposure; Zinc
PubMed: 7806447
DOI: 10.2486/indhealth.32.67 -
Antimicrobial Agents and Chemotherapy May 1994The in vitro activities of two glycylcyclines, CL 329,998 and CL 331,002 (two new semisynthetic tetracyclines), were evaluated in comparison with those of tetracycline... (Comparative Study)
Comparative Study
The in vitro activities of two glycylcyclines, CL 329,998 and CL 331,002 (two new semisynthetic tetracyclines), were evaluated in comparison with those of tetracycline and other available oral antimicrobial agents. A total of 523 recent clinical isolates were studied, including strains resistant to tetracycline. Members of the family Enterobacteriaceae were generally > or = 16-fold more susceptible to the glycylcyclines than to tetracycline (although less difference was seen with Proteus spp.). Pseudomonas aeruginosa was modestly susceptible to both new compounds (MIC for 90% of strains tested [MIC90], 16 micrograms/ml). Tetracycline- and methicillin-susceptible and -resistant strains of Staphylococcus aureus were all susceptible to the glycylcyclines (MIC90 < or = 1 microgram/ml). Streptococci (including Streptococcus pneumoniae) and Enterococcus faecalis and Enterococcus faecium displayed a bimodal distribution of susceptibility to tetracycline yet were uniformly susceptible to the glycylcyclines (MIC90 < or = 0.25 microgram/ml). The glycylcyclines were highly potent against Neisseria, Moraxella, Haemophilus, and Bacteroides spp. (MIC90 < or = 0.5 microgram/ml). Strains of Chlamydia spp. (three C. trachomatis strains and one C. pneumoniae strain) were inhibited by < or = 0.25 microgram of CL 329,998 or CL 331,002 per ml. Two strains of Mycoplasma pneumoniae were inhibited by < or = 0.12 microgram of CL 331,002 per ml and by 1 microgram of CL 329,998 per ml. Mycobacterium tuberculosis and Mycobacterium avium were resistant to the two glycylcyclines (MIC > or = 8 micrograms/ml). These results indicate that the two glycylcyclines have potent in vitro activities against a wide range of clinically important pathogenic bacteria.
Topics: Bacteria; Microbial Sensitivity Tests; Minocycline; Tetracycline Resistance; Tetracyclines
PubMed: 8067744
DOI: 10.1128/AAC.38.5.1096 -
Journal of Clinical Microbiology Aug 1996A collection of 300 Haemophilus influenzae clinical strains was used to assess in vitro susceptibility to carbapenems (meropenem, imipenem) by MIC and disk diffusion... (Comparative Study)
Comparative Study
A collection of 300 Haemophilus influenzae clinical strains was used to assess in vitro susceptibility to carbapenems (meropenem, imipenem) by MIC and disk diffusion methods and to compare disk diffusion test results with two potencies of ampicillin disks (2 and 10 micrograms). The isolates included ampicillin-susceptible or- intermediate (167 strains), beta-lactamase-positive (117 strains), and beta-lactamase-negative ampicillin-resistant (BLNAR; 16 strains) organisms. Disk diffusion testing was performed with 10-micrograms meropenem disks from two manufacturers. Meropenem was highly active against H. influenzae strains (MIC50, 0.06 microgram/ml; MIC90, 0.25 microgram/ml; MIC50 and MIC90, MICs at which 50 and 90%, respectively, of strains are inhibited) and was 8- to 16-fold more potent than imipenem (MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml). Five non-imipenem-susceptible strains were identified (MIC, 8 micrograms/ml), but the disk diffusion test indicated susceptibility (zone diameters, 18 to 21 mm). MIC values of meropenem, doxycycline, ceftazidime, and ceftriaxone for BLNAR strains were two- to fourfold greater than those for other strains. The performance of both meropenem disks was comparable and considered acceptable. A single susceptible interpretive zone diameter of > or = 17 mm (MIC, < = or 4 micrograms/ml) was proposed for meropenem. Testing with the 2-micrograms ampicillin disk was preferred because of an excellent correlation between MIC values and zone diameters (r = 0.94) and superior interpretive accuracy with the susceptible criteria at > or = 17 mm (MIC, < or = 1 microgram/ml) and the resistant criteria at < or = 13 mm (MIC, > or = 4 micrograms/ml). Among the BLNAR strains tested, 81.3% were miscategorized as susceptible or intermediate when the 10-micrograms ampicillin disk was used, while the 2-micrograms disk produced only minor interpretive errors (12.5%). Use of these criteria for testing H. influenzae against meropenem and ampicillin should maximize reference test and standardized disk diffusion test performance with the Haemophilus Test Medium. The imipenem disk diffusion test appears compromised and should be used with caution for detecting strains for which imipenem MICs are elevated.
Topics: Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; Data Interpretation, Statistical; Diffusion; Evaluation Studies as Topic; Haemophilus influenzae; Imipenem; Linear Models; Meropenem; Microbial Sensitivity Tests; Thienamycins; beta-Lactam Resistance
PubMed: 8818892
DOI: 10.1128/jcm.34.8.1970-1974.1996 -
Antimicrobial Agents and Chemotherapy Feb 1994The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella...
In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species.
The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml). Erythromycin (1 microgram/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.
Topics: Animals; Ceftriaxone; Cells, Cultured; Clavulanic Acid; Clavulanic Acids; Drug Interactions; Drug Therapy, Combination; Extracellular Space; Guinea Pigs; Intracellular Fluid; Legionella; Legionella pneumophila; Legionnaires' Disease; Macrophages, Alveolar; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Tazobactam
PubMed: 8192443
DOI: 10.1128/AAC.38.2.200 -
Journal of Dairy Science Aug 1993The antimicrobial susceptibility of 37 strains of bifidobacteria to 18 antimicrobial agents was determined by a macrodilution broth method. Most of the strains used were...
The antimicrobial susceptibility of 37 strains of bifidobacteria to 18 antimicrobial agents was determined by a macrodilution broth method. Most of the strains used were isolated from commercial yogurts and starters. Tested organisms were usually sensitive to Gram-positive spectrum antibiotics (bacitracin, erythromycin, lincomycin, and vancomycin), and most of the organisms were inhibited by a concentration < 1.56 micrograms/ml. Erythromycin was the most active agent; all strains were inhibited by < .19 microgram/ml. beta-Lactam antibiotics (penicillin G, ampicillin, methicillin, and cephalothin), showing a wide range of minimum inhibitory concentration, were less effective than Gram-positive spectrum antibiotics. Most strains were somewhat resistant to cephalothin, exhibiting inhibition at concentrations of 6.25 to 25.0 micrograms/ml. Test organisms were most resistant to kanamycin, neomycin, paromomycin sulfate, nalidixic acid, and polymyxin B sulfate; inhibition occurred only at > or = 50 micrograms/ml, and strains were somewhat less resistant to gentamicin and streptomycin. Susceptibility to nitrofurantoin and tetracycline was variable; minimum inhibitory concentrations ranged from 1.56 to 50.0 and .39 to 50.0 micrograms/ml, respectively, but chloramphenicol had a narrow range from 1.56 to 6.25 micrograms/ml.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bifidobacterium; Drug Resistance, Microbial; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Lactams; Microbial Sensitivity Tests
PubMed: 8408866
DOI: 10.3168/jds.S0022-0302(93)77553-0 -
British Journal of Anaesthesia Dec 1992We have measured concentrations of etomidate and thiopentone in maternal plasma, umbilical venous plasma and colostrum after induction of anaesthesia in 40 patients...
We have measured concentrations of etomidate and thiopentone in maternal plasma, umbilical venous plasma and colostrum after induction of anaesthesia in 40 patients undergoing Caesarean section. Mean plasma etomidate concentration declined rapidly (1242.0 ng ml-1 at 5 min, 434.0 ng ml-1 at 15 min, 64.2 ng ml-1 at 30 min, 7.0 ng ml-1 at 60 min and undetectable 2 h after the injection). Mean plasma concentrations of thiopentone declined more slowly (6.09 micrograms ml-1 at 5 min, 2.64 micrograms ml-1 at 2 h, 1.35 micrograms ml-1 at 4 h, 0.86 microgram ml-1 at 9 h and 0.59 micrograms ml-1 at 12 h). Mean umbilical venous thiopentone concentration was 4.72 micrograms ml-1, whereas the thiopentone concentration in the maternal sample at 5 min was 6.09 micrograms ml-1, giving an umbilical:maternal vein ratio of 1:1.3. Mean umbilical etomidate concentration was 51.7 ng ml-1 and the corresponding maternal vein sample (5 min) was 1242.0 ng ml-1 (P < 0.001), giving an umbilical:maternal vein ratio of 1:24. Mean concentrations of thiopentone in colostrum were 1.98 micrograms ml-1 at 30 min, 0.91 microgram ml-1 at 4 h and 0.59 microgram ml-1 at 9 h, colostrum:plasma ratios at 4 h and 9 h being 0.67 and 0.68, respectively. Mean concentrations of etomidate in colostrum were 79.3 ng ml-1 at 30 min and 16.3 ng ml-1 at 2 h, being undetectable at 4 h. The colostrum:plasma etomidate concentration ratio was 1.2 at 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Anesthesia, Intravenous; Anesthesia, Obstetrical; Cesarean Section; Colostrum; Etomidate; Female; Fetal Blood; Humans; Pregnancy; Thiopental
PubMed: 1467101
DOI: 10.1093/bja/69.6.586