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Biomedical subjects

K Y Yuen

Publications and source records attributed to K Y Yuen.

At least 127 records · Page 7Linked to original sources

Clarithromycin attenuates cyclophosphamide-induced mucositis in mice.

No universally recognized agent is available for prophylaxis or therapy of mucositis induced by chemotherapy or chemo-radiotherapy. The effect of clarithromycin on the severity of mucositis induced by cyclophosphamide was investigated using a mouse model. Four cross-sections of small intestine (levels A, B, C, and D) were taken at equivalent intervals at day 5 after cyclophosphamide (400 mg kg(-1)) administration. The sections were stained with haematoxylin and eosin, and were graded for the degree of mucositis histologically. At section level B, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone group (P<0.05). At levels B and C, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the normal saline (NS) group (P<0.05). At level C, the number of mice with grade 2 mucositis in the ceftriaxone group was significantly greater than that in the NS group (P<0.05). When the number of sections at all levels were analyzed together, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone and NS groups (P<0.05). The present observation suggests that clarithromycin and ceftriaxone attenuates and aggravates cyclophosphamide-induced mucositis. It prompts clinical trials in bone marrow transplant (BMT) recipients receiving cyclophosphamide for conditioning, and reconsideration in the use of ceftriaxone in the treatment of neutropenic fever in BMT recipients.

Animals↗

Cellulitis complicating lymphoedema.

In ten hospitalised patients with cellulitis complicating lymphoedema encountered over a 3-year period (1996-1998), the underlying diseases were carcinoma of the cervix (n = 4), uterus (n = 1), vagina (n = 1), breast (n=2) and nasopharynx (n= 1), and retroperitoneal squamous cell carcinoma (n = 1). Three of the ten patients had positive blood cultures, compared to none of the 20 age-matched, sex-matched controls hospitalised for cellulitis without lymphoedema. The mean duration of fever, tachycardia and cellulitis was significantly longer in patients with lymphoedema than in those without (P<0.05, P<0.05, and P<0.005 respectively). Early treatment initiated by patients themselves may help stop bacterial replication in the initial stages and minimise further damage to the lymphatic system.

Adult↗

Bacteremia due to Staphylococcus aureus with reduced susceptibility to vancomycin.

Four cases of bacteremia caused by Staphylococcus aureus with heteroresistance to vancomycin (hetero-VRSA) were described. In at least two of these four mortalities, the cause of death was temporally related to the hetero-VRSA bacteremia. The vancomycin and teicoplanin MICs of the resistant subpopulations of these four hetero-VRSA were 8 and 24 microg/ml, respectively. All isolates were producers of beta-lactamase, produced penicillin-binding protein PBP2a, and possessed the mecA gene accounting for methicillin resistance. Thickening of the peptidoglycan cell wall was observed by electron microscopy. When ampicillin was combined with vancomycin, in vitro synergism was detected using the checkerboard titration method (epsilonFIC = 0.13). The use of vancomycin plus ampicillin-sulbactam could be a viable option in treating severe hetero-VRSA infection in view of the higher affinity of ampicillin toward PBP2a.

Aged↗

Aspergillosis in bone marrow transplant recipients.

Invasive aspergillosis in bone marrow transplant recipient is associated with a high mortality. Diagnosis is often delayed because the inflammatory response is blunted by immunosuppression. The gold standard of tissue biopsy is often considered too in invasive as the procedure is often complicated by bleeding and secondary infection. Recent finding on non-invasive tests such as serial measurement of peripheral blood galactomannan antigen or DNA appears to be promising. However, the limited availability of such tests and requirement for expertise are still hampering their use in routine clinical management. More often than not, initiation of antifungal therapy is empirical and based on suggestive radiological changes. Amphotericin B remains the gold standard of therapy but liposconal preparation may prove to be less nephrotoxic and equally effective. Treatment outcome depends more on the acceleration of the recovery of the immune system and the reduction of anti-GVHD therapy than the antifungal agent followed by surgical resection. The efficacy of many reported anti-aspergillosis prophylactic regimen has not been proved in randomized control trials. Despite the absence of data, such policy should still be considered in transplant units with high incidence of aspergillus or undergoing renovation.

Air Microbiology↗

Comparison of screening methods for detection of extended-spectrum beta-lactamases and their prevalence among Escherichia coli and Klebsiella species in Hong Kong.

Three tests, the disk diffusion test, the double-disc synergy test and the inhibitor-potentiated disc diffusion test, were compared for their abilities to detect production of extended-spectrum beta-lactamases (ESBL) in 702 Escherichia coli and 472 Klebsiella spp. strains from four hospitals. Eleven percent E. coli and 13% Klebsiella spp. were found to produce ESBL. As an indicator of ESBL activity, the sensitivities of the five extended-spectrum beta-lactams were as follows: cefotaxime (100%), cefpodoxime (99.3%), ceftriaxone (98.6%), aztreonam (93%) and ceftazidime (57.7%) when interpreted using the National Committee for Clinical Laboratory Standards criteria. Their positive predictive values ranged from 67.8-83.8%. Both the inhibitor-potentiated disc diffusion test and the double-disc synergy test (at three inter-disc widths of 20, 25 and 30 mm) were capable of identifying all the ESBL-producers. However, at a single inter-disc width of 30 mm, the double-disc synergy test has limited sensitivity (83.8%). As a second test for confirming ESBL activity in strains with reduced susceptibility to beta-lactams, the inhibitor-potentiated disc diffusion test is therefore a simple and reliable option.

Escherichia coli↗

Enhancement of humoral and protective immune response induced by live-attenuated Salmonella typhi by ampicillin.

Efficacy of live-attenuated Salmonella vaccines delivered by the mucosal route is limited by the dose and interference from mucosal flora of the alimentary tract. In a mouse model, the total antibody response towards lipopolysaccharide of S. typhi was significantly enhanced at day 21 post-immunization with live-attenuated S. typhi (Ty21a) when ampicillin was concomitantly administered (p<0.005), and the lethal dose 50 of mice in the ampicillin and control groups immunized with Ty21a after wild-type S. typhi challenge on day 24 was 4x10(7) and 1x10(7), respectively. The faecal bacterial counts of the ampicillin group at days 1 and 3 were significantly lower than those of the control group (p<0.01 and <0.05). On day 1, the number of mice with > or =10 Ty21a colonies isolated from the spleen was significantly higher in the ampicillin group than the control group (p<0.05). Furthermore, on the same day, Ty21a was isolated from the faeces of three mice from the ampicillin group, but only one from the control group. We conclude that ampicillin may have enhanced the humoral and protective immune responses by giving the Ty21a a selective advantage over the normal bacterial flora. This concept of antibiotic enhancement of immunization could have important implications for other live-attenuated vaccines, as well as the delivery of microbial antigens and DNA vaccines by live-attenuated Salmonella carriers.

Ampicillin↗

Isolated splenic tuberculosis presenting with pyrexia of unknown origin.

We report a case of a 62-y-old man who presented with fever, malaise and weight loss. He was diagnosed with pyrexia of unknown origin due to tuberculosis of the spleen. Combination anti-tuberculous therapy was administered and fever gradually subsided after 6 weeks. A 12-month course of anti-tuberculous treatment would appear to be appropriate for the treatment of most patients with splenic tuberculosis.

Antitubercular Agents↗

beta-lactamases in Shigella flexneri isolates from Hong Kong and Shanghai and a novel OXA-1-like beta-lactamase, OXA-30.

Ninety-one ampicillin-resistant Shigella flexneri strains from Hong Kong and Shanghai were studied for production of beta-lactamases. TEM-1-like and OXA-1-like enzymes were identified in 21 and 79% of the strains, respectively, by isoelectric focusing (IEF). No difference in the pattern of beta-lactamase production was found between strains from Hong Kong and Shanghai. Four ribotypes were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1-like strains harbored a plasmid which hybridized positively with the bla(TEM) probe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel. The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned, sequenced, and found to differ from bla(OXA-1) at codon 131 (AGA-->GGA; Arg to Gly), resulting in the novel designation OXA-30. The predominance of OXA-type enzymes in ampicillin-resistant S. flexneri suggests host preference for specific beta-lactamases.

Anti-Bacterial Agents↗

Enhancement by ampicillin of antibody responses induced by a protein antigen and a DNA vaccine carried by live-attenuated Salmonella enterica serovar Typhi.

Live-attenuated Salmonella species are effective carriers of microbial antigens and DNA vaccines. In a mouse model, the immunoglobulin M (IgM) and total antibody levels directed toward the lipopolysaccharide of Salmonella enterica serovar Typhi were significantly enhanced at day 21 after oral immunization with live-attenuated serovar Typhi (strain Ty21a) when ampicillin was concomitantly administered (P < 0.05 and P < 0.005, respectively). The heat-killed Ty21a-stimulated lymphocyte proliferation indices for the ampicillin group at day 21 were significantly higher than those for the normal saline (NS) group (P < 0.005, P < 0.001, and P < 0.01) for all three doses of antigen (10(4), 10(5), and 10(6) heat-killed Ty21a per well, respectively). The 50% lethal doses for mice from the ampicillin and NS groups immunized with Ty21a with pBR322 after wild-type serovar Typhi challenge on day 24 were 3.4 x 10(7) and 5.0 x 10(6) CFU, respectively. The fecal bacterial counts for the ampicillin group at days 1, 3, and 5 were significantly lower than those for the NS group (P < 0.01, P < 0.01, and P < 0.05, respectively), and there was a trend toward recovery of Ty21a in a larger number of mice from the ampicillin group than from the NS group. Furthermore, the IgG2a levels directed toward tetanus toxoid were significantly enhanced at days 7 and 21 after oral immunization with Ty21a that carried the fragment c of tetanus toxoid when ampicillin was concomitantly administered (P < 0.05 and P < 0.005, respectively), and the IgM and total hepatitis B surface antibody levels were significantly enhanced at days 7 (P < 0.005 and P < 0.05, respectively) and 21 (P < 0.01 and P < 0.05, respectively) after oral immunization with Ty21a that carried the DNA vaccine that encodes hepatitis B surface antigen when ampicillin was concomitantly administered. The present observation may improve the efficacy of the protein antigens and DNA vaccines carried in live-attenuated bacteria, and further experiments should be carried out to determine the best antibiotics and dosage regimen to be used, as well as the best carrier system for individual protein antigens and DNA vaccines.

Ampicillin↗

Clarithromycin attenuates mastectomy-induced acute inflammatory response.

Based on the observation that administration of clarithromycin led to an attenuation of the inflammatory response induced by surgical trauma in a guinea pig model, we investigated the potential beneficial effects of clarithromycin on the local and systemic inflammatory response in patients undergoing mastectomy in an open-label prospective study. During a 16-month period, 54 patients who underwent mastectomy were randomly divided into two groups. In one group, the patients received oral clarithromycin at a dose of 500 mg twice a day, from the day before to 3 days after mastectomy. There was no significant difference in the incidence of antibiotic prophylaxis-related toxicities or postoperative infections between the patients who received clarithromycin and those who did not. Clarithromycin treatment was significantly associated with an attenuation of febrile response, tachycardia, tachypnea, and an increase in monocyte counts (P, <0.0001, <0.01, <0.05, and <0.01, respectively). Clarithromycin also reduced the intensity and duration of postoperative pain (P, <0.05 and <0.005, respectively) and increased the range of motion of the involved shoulder (P < 0.05 for abduction and flexion). We conclude that clarithromycin effectively modulates the acute inflammatory response associated with mastectomy and produces a better clinical outcome.

Acute-Phase Reaction↗

Identification of Mycobacterium neoaurum isolated from a neutropenic patient with catheter-related bacteremia by 16S rRNA sequencing.

A rapidly growing pigmented mycobacterial strain with an ambiguous biochemical profile was isolated from the blood culture taken through the Hickman catheter of a 9-year-old girl with acute lymphoblastic leukemia. Whole-cell fatty acid analysis showed that the best match profile was that of Mycobacterium aurum, but the similarity index was only 0.217, meaning that there were no good matches between the isolate and the organisms in the database of the Microbial Identification System. The 16S rRNA gene of the mycobacterial strain was amplified, agarose gel purified, and sequenced. There were 44 base differences between the gene sequence of the isolate and that of M. aurum but only one base difference between the sequence of the isolate and that of Mycobacterium neoaurum, showing that the isolate was indeed a strain of M. neoaurum by using this "gold standard." This represents the first case of M. neoaurum infection documented by 16S rRNA sequencing.

Bacteremia↗

Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae species from a bone marrow transplant recipient.

AIMS: To ascertain the clinical relevance of a strain of Enterobacteriaceae isolated from the stool of a bone marrow transplant recipient with diarrhoea. The isolate could not be identified to the genus level by conventional phenotypic methods and required 16S ribosomal RNA (rRNA) gene sequencing for full identification. METHODS: The isolate was investigated phenotypically by standard biochemical methods using conventional biochemical tests and two commercially available systems, the Vitek (GNI+) and API (20E) systems. Genotypically, the 16S bacterial rRNA gene was amplified by the polymerase chain reaction (PCR) and sequenced. The sequence of the PCR product was compared with known 16S rRNA gene sequences in the GenBank database by multiple sequence alignment. RESULTS: Conventional biochemical tests did not reveal a pattern resembling any known member of the Enterobacteriaceae family. The isolate was identified as Salmonella arizonae (73%) and Escherichia coli (76%) by the Vitek (GNI+) and API (20E) systems, respectively. 16S rRNA sequencing showed that there was only one base difference between the isolate and E coli K-12, but 48 and 47 base differences between the isolate and S typhimurium (NCTC 8391) and S typhi (St111), respectively, showing that it was an E coli strain. The patient did not require any specific treatment and the diarrhoea subsided spontaneously. CONCLUSIONS: 16S rRNA gene sequencing was useful in ascertaining the clinical relevance of the strain of Enterobacteriaceae isolated from the stool of the bone marrow transplant recipient with diarrhoea.

Adult↗

Human infection with influenza H9N2.

We report the clinical features of two cases of human infection with influenza A virus subtype H9N2 in Hong Kong, and show that serum samples from blood donors in Hong Kong had neutralising antibody suggestive of prior infection with influenza H9N2.

Animals↗

Clarithromycin attenuates the inflammatory response induced by surgical trauma in a guinea pig model.

The effect of clarithromycin on the systemic and local inflammatory responses after surgical trauma was investigated using a guinea pig model. There was no statistically significant difference in the body temperature and respiratory rate of the guinea pigs between the clarithromycin and control groups, although there was a trend towards a lower temperature in the first 36 h after the operation, and a trend towards a lower respiratory rate on day 1 and day 2 (P=0.07 and 0.18, respectively) in the clarithromycin group. The total leukocyte count of both groups of animals increased from day -1 to day 4, and the increase was more marked in the control group (P=0.06 on day 1). The neutrophil and monocyte counts of the two groups of animals also increased after the operation. The neutrophil count of the control group was significantly higher than the clarithromycin group on day 1 and 2 (P<0.05 and 0.01, respectively), and the monocyte count of the control group was significantly higher than the clarithromycin group on day 1 (P<0.005). Moreover, the platelet count of the animals also increased after the operation, and the count in the control group was significantly higher than the clarithromycin group on day 1, 2 and 4 (P<0.05, 0.005 and 0.005, respectively). There was no difference between the haemoglobin concentration, lymphocyte count, eosinophil count and basophil count between the two groups of animals. The number of animals with wound discharge was lower in the clarithromycin group than the control group throughout the post-operative period, but the difference was not statistically significant. None of the animals developed signs of wound infection. The present observation suggests that clarithromycin suppressed both the systemic and local inflammatory response after surgical trauma, and it prompts further animal experiments for delineation of the mechanism of action, as well as clinical trials in major surgical procedures.

Animals↗

Hot spot mutations in morphological transforming region II (ORF 79) of cytomegalovirus strains causing disease from bone marrow transplant recipients.

Nested polymerase chain reaction (PCR) amplifying the morphological transforming region II (mtrII) of cytomegalovirus (CMV) has been shown to be useful in the detection of CMV DNA in bone marrow transplant (BMT) recipients. However, there has never been any report on mutation hot spots and subtypes of this open reading frame. Using primers derived from sequences upstream and downstream of mtrII (ORF 79), CMV DNA from peripheral blood leukocytes (PBL) and conventional CMV culture of 16 BMT recipients were amplified by PCR, cloned into pUC118, and sequenced. The amino acid sequences were predicted using the standard triplet code. The DNA sequences obtained from direct amplification of CMV in PBL obtained from the 16 patients were 100% identical to the corresponding ones obtained by amplification of CMV DNA extracted from conventional CMV culture. Within mtrII (ORF 79), hot spot single base mutations were observed at positions +40 (G-->A), +123 (A-->G), +213 (T-->C), and +219 (T-->C). However, because of third base degeneracy, only amino acid 14 was changed from valine to isoleucine in the predicted protein of 13 patients. This corresponded to the hot spot mutation at position +40 (GTC-->ATC), while the rest were silent mutations. An insertion of 3 bases (ACG) was observed in the CMV DNA of 10 patients at positions +91 to +93, leading to a threonine insertion at amino acid 31 in these patients. For patient no. 147 there was a 65 bp deletion in the CMV DNA amplified later in the course of BMT as compared with that early in the course. This gave rise to a frame shift mutation and a change of more than 70% in the predicted amino acid sequence of the protein.

Amino Acid Sequence↗