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Biomedical subjects

B Saxon

Publications and source records attributed to B Saxon.

15 recordsLinked to original sources

Effect of factor VIII concentrate on leucocyte cytokine receptor expression in vitro: relevance to inhibitor formation and tolerance induction.

Inhibitor formation in haemophilia patients receiving factor VIII (FVIII) concentrate is a serious problem requiring tolerance induction therapy. Inhibitor antibody formation is dependent on interactions between leucocyte cytokines with their corresponding receptors. To investigate this we studied the effect of FVIII on cytokine receptor expression using multiparameter flow cytometry and a whole blood stimulation assay. Upregulation of many cytokine receptors was inhibited by plasma-derived FVIII (pdFVIII) in a dose-dependent manner on T cells, B cells and monocytes although interleukin (IL)-4Ralpha and IL-7Ralpha were upregulated on T cells. The decrease in cytokine receptor upregulation on B cells in the presence of pdFVIII, may result in reduced antibody production. Inhibition of CD132 in the presence of pdFVIII may result in immune tolerance in some recipients of pdFVIII. The immunomodulatory effects of pdFVIII were dose and batch dependent, some being more inhibitory than others. The inhibitory effects of prednisolone with pdFVIII, on cytokine receptor upregulation, were additive. Cytokine receptor expression was not altered in the presence of human recombinant FVIII (rFVIII) concentrate. These findings may explain the reports of less frequent inhibitor antibody formation in some recipients of pdFVIII concentrates. The use of pdFVIII, particularly the more inhibitory batches, may be more suitable than rFVIII for tolerance induction protocols. A clinical study needs to be undertaken to determine the significance of these in vitro findings.

B-Lymphocytes↗

Orbital rhabdomyosarcoma: multidisciplinary treatment experience.

Orbital rhabdomyosarcoma (RMS) accounts for 10% of childhood RMS and has a relatively good prognosis of up to 85% 5-year survival. Improved survival has led to increased interest in late effects of treatment. The objective of this study was to review the results of treating orbital RMS with multidisciplinary treatment at Women's and Children's Hospital and Royal Adelaide Hospital with emphasis on late effects of treatment. A retrospective review was carried out of all patients with orbital RMS treated with multidisciplinary treatment including radiation therapy and chemotherapy in the two institutions between 1982 and 2002. A total of five patients (age range 5.5-12 years) satisfied the eligibility requirements. Late effects were significant and included facial bone hypoplasia, cataract formation and growth hormone deficiency. Overall survival was 80% (4/5) with mean follow up of 8 years (range 3-13 years). Given the high cure rates achieved, future treatments must aim to maintain the good results but to reduce the high incidence of late effects of treatment. Standardised rating of late toxicity, long-term follow-up clinics, and implementation of modern radiation techniques (3-D conformal radiotherapy, intensity modulated radiotherapy, proton therapy) for patients with orbital RMS are important to improving outcome.

Child↗

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia.

OBJECTIVE: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia. METHODS: The medical records of 14 children who fulfilled the International Juvenile Myelomonocytic Leukaemia Working Group Criteria for a diagnosis of juvenile myelomonocytic leukaemia (JMML) presenting to a single institution were reviewed, and their clinical status at September 2000 was documented. RESULTS: The most common presenting features were hepatosplenomegaly and lymphadenopathy. Fifty per cent of cases presented in the first year of life. Nine of 14 patients initially received chemotherapy otherwise used in the treatment of acute myeloid or lymphoblastic leukaemia with no apparent benefit. All six patients who received conditioning therapy with chemotherapy alone, followed by allogeneic bone marrow transplant (BMT), are in complete remission at a median follow-up duration of 12 months (range 5-91 months). Five of six patients surviving post-allogeneic BMT received marrow from an unrelated donor. Only one of seven patients who did not receive BMT survived long-term. CONCLUSION: Children with a diagnosis of JMML should be treated with allogeneic BMT as soon as a suitable donor is found. The role of anti-leukaemic therapy in this disease, prior to BMT, requires further investigation in the context of a multicentre clinical trial.

Antineoplastic Agents↗

Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.

A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia developed a rapidly expanding red annular plaque on her thigh, initially without signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in the blood vessel walls. In immunocompromised individuals, skin biopsy and culture of cutaneous lesions for bacteria and fungi should be considered even in the absence of signs of systemic toxicity or multiple lesions.

Child, Preschool↗

Bones, groans and blasts.

A 14-year-old girl presented with the acute onset of gastrointestinal symptoms due to hypercalcaemia. Chest X-ray revealed osteolytic lesions in the ribs which in conjunction with a normal parathyroid hormone level raised the possibility of malignancy. Despite the absence of blast cells in her blood film, the bone marrow biopsy was diagnostic of acute lymphoblastic leukaemia. She responded well to treatment with pamidronate and chemotherapy.

Adolescent↗

Failure of Micro Media FOX Microdilution System to detect decreased susceptibility of Streptococcus pneumoniae to penicillin.

Twelve isolates of Streptococcus pneumoniae with decreased susceptibility by oxacillin screen were susceptible by the FOX panel (Micro Media Systems, Cleveland, Ohio), a commercial microdilution system designed for fastidious organisms. These organisms were found to be moderately susceptible or resistant by broth macrodilution and agar dilution methods. This discrepancy indicates that the FOX panel is not reliable for susceptibility testing of S. pneumoniae.

Diagnostic Errors↗

Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system.

Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested.

Amoxicillin↗

In vitro inactivation of aminoglycosides by cephalosporin antibiotics.

The in vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins complicates antibiotic assays. Due to the increasing number of new cephalosporins and use of aminoglycoside-cephalosporin combinations, we determined the in vitro stability of 28 aminoglycoside-cephalosporin combinations (gentamicin sulfate, tobramycin sulfate, netilmicin sulfate [10 micrograms/mL], and amikacin [20 micrograms/mL] in combination with cefazolin sodium, cefoxitin sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime acid pentahydrate, cefsulodin sodium, or cefpiramide sodium at 100, 200, and 300 micrograms/mL). These mixtures were incubated at 37 degrees C and sampled at 0, 8, and 24 hours. Amikacin and tobramycin were most stable and netilmicin was the least stable of the aminoglycosides. Cefoxitin, ceftazidime, and cefotaxime were the least inactivating of the cephalosporins. When combined with first- and second-generation cephalosporins, aminoglycosides are relatively stable, but some laboratory precautions may be necessary when determining aminoglycoside levels in the presence of third-generation cephalosporin compounds.

Aminoglycosides↗

In vitro activity in deptomycin (LY-146032) compared with other antimicrobial agents against gram-positive cocci.

A comparison was made of the activity of deptomycin (LY-146032) with that of ampicillin, cephalexin, cefamandole, cephalothin, erythromycin, teicoplanin, tetracycline, and vancomycin. The minimal inhibitory concentration (MICs) for greater than or equal to 90% of 356 Gram-positive cocci, against deptomycin, were less than or equal to 2 micrograms/ml. The MICs for the other antimicrobials varied greatly depending on the compound. A slight and unexplained inoculum effect was observed for LY-146032.

Anti-Bacterial Agents↗

Comparison of visual and photometric Bac-T-Screen results.

The Bac-T-Screen (Marion Laboratories, Kansas City, MO) was used to screen 826 urine specimens. Of these, 85 either pigmented or clogged the Bac-T-Screen filter and could not be evaluated. Results for the remaining 741 specimens were examined both visually and photometrically by a newly developed photometric card reader. The results were then compared. Screening results for all urines containing greater than or equal to 10(5) pathogens/mL were equivalent for both methods, with sensitivity and predictive negative values of greater than 98% and greater than 99%, respectively. The predictive values of positive tests were also equivalent at 57.5% for visual and 59.6% by photometry. The overall agreement varied with the card reader value used because the photometric card-reader procedure allows the user to select desired sensitivity and specificity levels.

Bacteriological Techniques↗

In vitro inactivation of aminoglycosides by apalcillin.

Apalcillin, at concentrations of 75, 150, 300, and 600 micrograms/ml, was combined in vitro with amikacin, gentamicin, netilmicin, or tobramycin. Incubation at 37 degrees C resulted in an apalcillin concentration-dependent and time-dependent decrease of aminoglycoside activity of up to 60%. Amikacin was the most stable and tobramycin was the least stable aminoglycoside under the conditions tested.

Amikacin↗

Use of the Bac-T-Screen to predict bacteriuria from urine specimens held at room temperature.

Results from the Bac-T-Screen (BTS) of fresh urine specimens were compared with the BTS results obtained when the same urine specimens had been held at room temperature for 24 h. Of the 246 specimens studied, 43 were initially BTS positive, 11 were false-negative, and 39 had greater than or equal to 10(5) CFU/ml. After 24 h at room temperature an additional 60 specimens had greater than or equal to 10(5) CFU/ml, of which only 16 were BTS positive; 10 specimens still gave false-negative results, and the number of false-positive specimens increased by only 6.5% of all specimens. For significant specimens (containing greater than or equal to 10(5) CFU of probable pathogens per ml), the predictive value of a negative test changed by only 0.1% (99.5 to 99.4%), whereas the sensitivity of the test remained at 96.4% for incubated specimens. Of those specimens that developed greater than or equal to 10(5) CFU/ml in vitro, 85% contained gram-negative bacilli. Neither bacteria grown in vitro nor urine specimens from normal females containing greater than or equal to 10(5) CFU/ml were positive with the BTS. For reasons not entirely understood, the BTS system may be unique in its ability to discriminate between bacteria which represent true bacteriuria and those which are present because of contamination, possibly due to other cellular elements present in infection-related bacteriuria, namely leukocytes and sloughed bladder epithelial cells.

Bacteriological Techniques↗

Effect of urine preservation on urine screening and organism identification.

Three urine preservation-transport methods were examined for their effect on rapid urine-screening procedures. Results from fresh urine specimens, screened for bacteriuria by leukocyte esterase, nitrate, Autobac, Bac-T-Screen, Auto Microbic System (AMS), and bioluminescence procedures, were compared with urine-screen results from urine specimens held for 24 hours at room temperature in chemical preservatives. Quantitative discrepancies ranged from 0%, for urine preserved with glycerin-boric acid-sodium formate and tested by AMS or leukocyte esterase, to 21% for urines in the same preservative tested by bioluminescence or nitrate. Up to 62% of the organism identifications made from preserved urine specimens tested by the AMS urine card were in error. These data suggest that it may be inadvisable to use weak organic acid-based urine preservation systems in conjunction with these urine-screen procedures.

Bacteriuria↗

Comparative in vitro activity of lomefloxacin (SC 47111 or NY-198) against fresh clinical bacterial isolates.

The in vitro antibacterial activity of a new difluorinated quinolone (lomefloxacin) was compared with that of ten selected antibiotics against 744 fresh bacterial isolates representing 32 species. Lomefloxacin was comparable to other quinolones tested against Enterobacteriaceae (MIC90, less than or equal to 0.25 micrograms/ml) and generally more effective than other compounds tested against Staphylococcus spp. and Pseudomonas aeruginosa with MIC90s of less than or equal to 2 and less than or equal to 4 micrograms/ml, respectively.

4-Quinolones↗