[Analysis of the correlative factors of long-term positive nucleic acid and the characteristics of nucleic acid conversion in novel coronavirus infected patients].

To analyze the correlative factors of long-term positive nucleic acid and the characteristics of negative nucleic acid conversion in novel coronavirus infected patients.Novel coronavirus infected patients who were hospitalized in Beijing Tsinghua Changgung Hospital from December 2022 to June 2023 were retrospectively included. Patients who were positive for novel coronavirus nucleic acid for ≥30 days were selected as the long-positive group, and age-and sex-matched patients with novel coronavirus nucleic acid for <30 days were selected as the control group. The clinical data of all enrolled patients were collected. Binary logistic regression was used to analyze the influencing factors of the positive duration of nucleic acid ≥30 days. The Cox risk ratio model was used to analyze the risk factors for the prognosis of severe patients during hospitalization, and the difference in the time of nucleic acid conversion between the upper and lower respiratory tract was compared between the groups. A total of 30 patients were included in the long-positive group, including 24 males and 6 females, aged [M (Q1, Q3)] 77 (64, 86) years. Fifty-eight patients were included in the control group, including 46 males and 12 females, aged 78 (66, 86) years. Transplantation status (OR=50.32, 95%CI: 1.98-1 278.63, P=0.018), malignant tumor (OR=12.85, 95%CI: 1.65-99.88, P=0.015), CD4+T cell count (OR=0.99, 95%CI: 0.99-1.00, P=0.005) were correlative factors for positive nucleic acid≥30 days. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score (HR=1.12, 95%CI: 1.03-1.22, P=0.012) and nucleic acid positive time (HR=1.16, 95%CI: 1.01-1.33, P=0.031) were correlative factors for death in severe patients. The nucleic acid conversion time of the lower respiratory tract specimens in both groups was later than that of the upper respiratory tract specimens (all P<0.001). Weakened underlying immunity is a correlative factor for long-term novel coronavirus nucleic acid positivity, and long-term positive novel coronavirus nucleic acid in severe patients indicates high risk of death. The nucleic acid of the lower respiratory tract specimen turned negative later than the upper respiratory tract specimen.

Bevacizumab in combination with first-line chemotherapy in patients with metastatic colorectal cancer: a meta-analysis.

Bevacizumab plays an important role in the treatment of patients with metastatic colorectal cancer (mCRC). The aim of this study is to assemble current RCTs to analyze efficacy of adding bevacizumab to the most used combination first-line chemotherapy in mCRC patients. PubMed, Web of Science, the Cochrane Library and Embase were systematically searched. Our primary endpoint was overall survival (OS), progression-free survival (PFS) and secondary endpoint was overall response rate (ORR). Hazard ratios (HRs) for PFS and OS and risk ratio (RR) for ORR were extracted from each trial. All these above were performed using a random-effects model and statistics was performed in StataSE 12.0. Seven randomized controlled studies aggregating 3264 patients were enrolled in our meta-analysis. OS, PFS and ORR were performed using a random-effects model. A therapeutic effect advantage was showed in Bevacizumab added to first-line chemotherapy with higher OS (HR=0.67; 95% CI=0.61-0.72; P=0.000), PFS (HR=0.67; 95% CI=0.61-0.72; P=0.000) compared with chemotherapy alone. Chemotherapy plus bevacizumab increased ORR (38.42% vs. 33.44%), showing statistically difference (RR=1.17, 95% CI=1.06-1.28, P=0.001). Our meta-analysis shows that the addition of bevacizumab to first-line regimens can be beneficial in terms of OS, PFS and ORR compared with chemotherapy alone.

Histone deacetylase inhibitors: Potential in cancer therapy.

The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation. There are 18 HDACs in humans. These enzymes are not redundant in function. Eleven of the HDACs are zinc dependent, classified on the basis of homology to yeast HDACs: Class I includes HDACs 1, 2, 3, and 8; Class IIA includes HDACs 4, 5, 7, and 9; Class IIB, HDACs 6 and 10; and Class IV, HDAC 11. Class III HDACs, sirtuins 1-7, have an absolute requirement for NAD(+), are not zinc dependent and generally not inhibited by compounds that inhibit zinc dependent deacetylases. In addition to histones, HDACs have many nonhistone protein substrates which have a role in regulation of gene expression, cell proliferation, cell migration, cell death, and angiogenesis. HDAC inhibitors (HDACi) have been discovered of different chemical structure. HDACi cause accumulation of acetylated forms of proteins which can alter their structure and function. HDACi can induce different phenotypes in various transformed cells, including growth arrest, apoptosis, reactive oxygen species facilitated cell death and mitotic cell death. Normal cells are relatively resistant to HDACi induced cell death. Several HDACi are in various stages of development, including clinical trials as monotherapy and in combination with other anti-cancer drugs and radiation. The first HDACi approved by the FDA for cancer therapy is suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza), approved for treatment of cutaneous T-cell lymphoma.

HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation.

Eighteen histone deacetylases (HDACs) are present in humans, categorized into two groups: zinc-dependent enzymes (HDAC1-11) and NAD(+)-dependent enzymes (sirtuins 1-7). Among zinc-dependent HDACs, HDAC6 is unique. It has a cytoplasmic localization, two catalytic sites, a ubiquitin-binding site, and it selectively deacetylases alpha-tubulin and Hsp90. Here, we report the discovery that the redox regulatory proteins, peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6. Prx are antioxidants enzymes whose main function is H(2)O(2) reduction. Prx are elevated in many cancers and neurodegenerative diseases. The acetylated form of Prx accumulates in the absence of an active HDAC6. Acetylation of Prx increases its reducing activity, its resistance to superoxidation, and its resistance to transition to high-molecular-mass complexes. Thus, HDAC6 and Prx are targets for modulating intracellular redox status in therapeutic strategies for disorders as disparate as cancers and neurodegenerative diseases.

Histone deacetylase inhibitors: molecular mechanisms of action.

This review focuses on the mechanisms of action of histone deacetylase (HDAC) inhibitors (HDACi), a group of recently discovered 'targeted' anticancer agents. There are 18 HDACs, which are generally divided into four classes, based on sequence homology to yeast counterparts. Classical HDACi such as the hydroxamic acid-based vorinostat (also known as SAHA and Zolinza) inhibits classes I, II and IV, but not the NAD+-dependent class III enzymes. In clinical trials, vorinostat has activity against hematologic and solid cancers at doses well tolerated by patients. In addition to histones, HDACs have many other protein substrates involved in regulation of gene expression, cell proliferation and cell death. Inhibition of HDACs causes accumulation of acetylated forms of these proteins, altering their function. Thus, HDACs are more properly called 'lysine deacetylases.' HDACi induces different phenotypes in various transformed cells, including growth arrest, activation of the extrinsic and/or intrinsic apoptotic pathways, autophagic cell death, reactive oxygen species (ROS)-induced cell death, mitotic cell death and senescence. In comparison, normal cells are relatively more resistant to HDACi-induced cell death. The plurality of mechanisms of HDACi-induced cell death reflects both the multiple substrates of HDACs and the heterogeneous patterns of molecular alterations present in different cancer cells.

Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.

This study examines the basis of resistance and sensitivity of normal and transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically the role of caspases and thioredoxin (Trx). An important attribute of HDACis is that they induce cancer cell death at concentrations to which normal cells are relatively resistant, making them well suited for cancer therapy. The mechanism underlying this selectivity has not been understood. In this study we found that the HDACi suberoylanilide hydroxamic acid (SAHA) and MS-275, a benzamide, cause an accumulation of reactive oxygen species (ROS) and caspase activation in transformed but not normal cells. Inhibition of caspases does not block HDACi-induced cell death. These studies provide a possible mechanism that can explain why normal but not certain transformed cells are resistant to HDACi-induced cell death. The HDACi causes an increase in the level of Trx, a major reducing protein for many targets, in normal cells but not in transformed cells. The SAHA-induced increase in Trx activity in normal cells is associated with no increase in ROS accumulation. Transfection of transformed cells with Trx small interfering RNA caused a marked decrease in the level of Trx protein with an increase in ROS, a decrease in cell proliferation, and an increase in sensitivity to SAHA-induced cell death. Thus, Trx, independent of the caspase apoptotic pathway, is an important determinant of resistance of cells to HDACi-induced cell death.

Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1.

Histone deacetylase (HDAC) inhibitors (HDACi) cause cancer cell growth arrest and/or apoptosis in vivo and in vitro. The HDACi suberoylanilide hydroxamic acid (SAHA) is in phase I/II clinical trials showing significant anticancer activity. Despite wide distribution of HDACs in chromatin, SAHA alters the expression of few genes in transformed cells. p21(WAF1) is one of the most commonly induced. SAHA does not alter the expression of p27(KIPI), an actively transcribed gene, or globin, a silent gene, in ARP-1 cells. Here we studied SAHA-induced changes in the p21(WAF1) promoter of ARP-1 cells to better understand the mechanism of HDACi gene activation. Within 1 h, SAHA caused modifications in acetylation and methylation of core histones and increased DNase I sensitivity and restriction enzyme accessibility in the p21(WAF1) promoter. These changes did not occur in the p27(KIPI) or epsilon-globin gene-related histones. The HDACi caused a marked decrease in HDAC1 and Myc and an increase in RNA polymerase II in proteins bound to the p21(WAF1) promoter. Thus, this study identifies effects of SAHA on p21(WAF1)-associated proteins that explain, at least in part, the selective effect of HDACi in altering gene expression.

Identification and characterization of BCL6 translocation partner genes in primary gastric high-grade B-cell lymphoma: heat shock protein 89 alpha is a novel fusion partner gene of BCL6.

Primary gastric high-grade B-cell lymphoma (HGBL) is a special type of non-Hodgkin's lymphoma. So far, the genetic features of this tumor have not been well characterized. Recently, a high incidence of BCL6 rearrangements has been detected in HGBL. However, no previous cytogenetic studies have found translocations involving the BCL6 locus (3q27) in HGBL, and the genetic basis underlying the BCL6 rearrangements in this tumor remains unclear. We therefore characterized the partner genes of BCL6 in five primary gastric HGBLs with a rearranged BCL6 gene by analyzing BCL6 transcripts using the 5' RACE (rapid amplification of cDNA end) strategy. BCL6 translocation partner genes were identified at the 5' end of the chimeric transcripts in all five cases, including the immunoglobulin heavy-chain (IGH) gene in three cases and the immunoglobulin lambda-light-chain gene and the heat shock protein 89 alpha (HSP89A) gene in the other two cases. The chimeric transcripts in all cases contained the intact BCL6 exon 2, but lacked exon 1, which was replaced by sequences from the partner genes, suggesting that BCL6 expression was under the control of regulatory sequences of the partner genes. These results, for the first time, indicate that immunoglobulin genes, especially IGH, are the most common BCL6 translocation partner genes in primary gastric HGBL and that HSP89A is a novel partner of BCL6. Because immunoglobulin genes are also the most frequent partners of BCL6 in nodal diffuse large B-cell lymphoma (DLBCL), these data suggest that primary gastric HGBL shares a common genetic basis with nodal DLBCL. Genes Chromosomes Cancer 27:69-75, 2000.

Epstein-Barr virus infection and its gene expression in gastric lymphoma of mucosa-associated lymphoid tissue.

The role of Epstein-Barr virus (EBV) in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has not been well understood. The aim of the study was to investigate EBV infection and its gene expression in this tumor in order to understand its role in the pathogenesis. EBV infection was screened by in situ hybridization for EBV-encoded non-polyadenylated RNA (EBER ISH) in 79 cases of gastric MALT lymphoma of nonimmunocompromised patients. The expression of EBV proteins [LMP1 (latent membrane protein 1), EBNA2 (EBV nuclear antigen 2), ZEBRA (switch protein encoded by BZLF1 gene)] was studied by immunohistochemistry in EBER-positive cases. EBV was detected with EBER ISH in 15 (19%) of the 79 cases. EBV was found in virtually all tumor cells in 2 cases of high-grade MALT lymphoma (2.5%) (EBV-associated), and was found only in occasional large or small lymphoid cells in 13 cases (16.5%). False positive EBER signal was detected in the mucinous glandular epithelial cells of gastric antrum with FITC-labeled oligonucleotide probe but not with digoxigenin or 35S-labeled riboprobes. Type II latency (EBER+LMP1+ EBNA2-) was detected in both EBV-associated cases. Type III latency (EBER+LMP1+EBNA2+) was also identified in one EBV-associated case besides latency II. Double labeling showed coexpression of LMP1 and EBNA2 in a small number of tumor cells, indicating the presence of type III latency in single cell level. In cases with only occasional EBER-positive large or small lymphoid cells, LMP1 and EBNA2 were not detected. ZEBRA was negative in all the cases. These findings suggest that EBV may contribute to the pathogenesis of a small proportion of high-grade MALT lymphoma, where virtually all tumor cells harbored EBV and the oncogenic viral protein LMP1 was expressed. Moreover, latency III of EBV infection may exist in nonimmunocompromised patient.

Detection of trisomy 3 in primary gastric B-cell lymphoma by using chromosome in situ hybridization on paraffin sections.

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.

No evidence of replication error phenotype in primary gastric lymphoma of mucosa-associated lymphoid tissue.

Replication error (RER) phenotype, caused by deficiency of DNA mismatch repair genes and revealed by widespread microsatellite instability, has been detected in subsets of a wide variety of solid tumors, but rarely in lymphomas in general. So far, the involvement of RER phenotype in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type has not been conclusively established. We therefore examined 9 microsatellite loci on 5 chromosomes [D2S123, D3S11, D3S1261, D3S1262, D3S1265, D6S262, D18S559, a CTTT(T) repeat in intron 20 of RBI gene and a CA repeat in p53 locus] in 33 cases of primary gastric MALT lymphoma for evidence of microsatellite instability by polymerase chain reaction using primers end-labeled with [gamma-33P] ATP. Although novel-length allele was observed in 7 of 33 cases (21.2%), none of these 7 cases showed changes in more than one locus. RER phenotype was scored as positive in a case when more than 1 of the 9 examined microsatellite loci showed length alterations. Accordingly, none of the 33 cases had a RER phenotype. This result suggests that the pathogenesis of gastric MALT lymphoma does not involve RER phenotype. It is consistent with the general observations in lymphomas, but is highly in contrast to a previous report showing more than 50% of MALT lymphomas with the RER phenotype.

Mutation of the 5' noncoding region of the BCL-6 gene in low-grade gastric lymphoma of the mucosa-associated lymphoid tissue.

BCL-6 gene rearrangement and hypermutations were investigated in four Hong Kong Chinese patients with low-grade gastric lymphoma of the mucosa-associated lymphoid tissue (MALToma). The former was studied by Southern analysis and the latter by the technique of polymerase chain reaction and denaturing gradient gel electrophoresis. BCL-6 gene rearrangement was not detectable in any of the four cases. However, mutations at both the E1.11 and E1.12 segments of the 5' noncoding region of the BCL-6 gene were found in two patients. This preliminary observation suggests that the mutations of the 5' noncoding region of the BCL-6 gene rather than gene rearrangement may be playing a more important role in the tumorigenesis of low-grade gastric MALToma. Further confirmation of this finding by studying a larger number of patients will be required.

Bcl-6 gene hypermutations in diffuse large B-cell lymphoma of primary gastric origin.

The presence of the bcl-6 gene hypermutation was studied in 40 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary sites of involvement were nodal in 18 cases and gastric in 22. Hypermutations at the E1.11 segment of bcl-6 gene were detectable in 16/22 (73%) primary gastric and 4/18 (22%) primary nodal lymphoma (P<0.01). Three of the 22 cases of primary gastric but none of the nodal lymphoma had mutations at E1.12. The proportion of hypermutated cases in the group with bcl-6 gene rearrangement was similar to that of the germ-line group (70% v 75%). High frequency of bcl-6 gene hypermutations was found in diffuse large B-cell lymphoma of the stomach and they were independent of rearrangement of the gene as detected by Southern analysis. Unlike gene rearrangement, hypermutations of the bcl-6 gene did not appear to carry any prognostic significance clinically.

High incidence of BCL-6 gene rearrangement in diffuse large B-cell lymphoma of primary gastric origin.

The incidence of BCL-6 gene rearrangement was studied in 39 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary site of involvement was nodal in 18 cases and gastric in 21 cases. Clonal BCL-6 gene rearrangement was found in 17% of the patients with primary nodal and 48% with primary gastric lymphoma (p = 0.05). The clinical characteristics and treatment outcome of the 21 patients with primary gastric lymphoma were analyzed according to the BCL-6 status. Significantly more patients in the germline BCL-6 gene group had advanced stage (II, III and IV) of disease. Complete remission rate following primary therapy appeared to be higher for the positive rearrangement group (70% versus 36%), but it was not statistically significant. Those with a rearranged BCL-6 gene also appeared to have better survival at 5 years (58% versus 36%) but the difference was also not statistically significant. On the other hand, patients being classified as low risk according to the International Prognostic Index had significantly better survival at 5 years (89% versus 9%, p = 0.0001). We concluded that BCL-6 gene rearrangement was more commonly found in diffuse large B-cell lymphoma of primary gastric origin than its nodal counterpart and it may be playing a more important role in the pathogenesis of gastric large B-cell lymphoma. There was a trend that the BCL-6 gene rearrangement was associated with a more favorable outcome in patients with gastric large B-cell lymphoma but the difference was not statistically significant.

Pathogenesis of gastric lymphoma: the enigma in Hong Kong.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been postulated to be a pathogenetic factor in gastric lymphoma. However, the etiological factors for gastric lymphoma could vary in different populations. MATERIALS AND METHODS: We looked for histological evidence of H. pylori infection in 53 gastrectomy specimens from Hong Kong Chinese patients with primary gastric B-lymphoma. We also screened for Epstein-Barr virus (EBV) in these cases using in situ hybridization with oligonucleotide probes for EBV-encoded small RNA1 and 2. RESULTS: H. pylori was found in 29 of 53 (55%), including 8 of 13 (62%) cases of low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) type. These infection rates in gastric lymphoma are lower than those reported in Western populations (80%-100%) and comparable to that found in healthy Chinese blood donors (55%) or in non-ulcer dyspeptic patients (52%-57%). EBV was found in tumor cells only in one case of high-grade gastric lymphoma with low-grade MALT component which was H. pylori-negative, and in occasional nontumor-lymphoid cells in 7 other cases. CONCLUSIONS: These results suggest that (1) the role of H. pylori in pathogenesis of gastric lymphoma may vary in different populations; (2) very few gastric lymphomas are associated with EBV; (3) not all low-grade gastric MALT lymphomas are H. pylori-dependent.

Immunization with interleukin-2/interferon-gamma double cytokine-secreting allogeneic fibroblasts prolongs the survival of mice with melanoma.

LM mouse fibroblasts (H-2k) were modified for the expression of (antibody-defined) melanoma-associated antigens (MAA) and the secretion of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) (RLBA-IL-2/IFN-gamma cells). The cell construct was tested for its immunogenic properties in C57BL/6 mice (H-2b) with B16 melanoma. The results indicated that the survival of mice injected with a mixture of B16 cells and the modified, double cytokine-secreting fibroblasts was significantly longer than that of mice injected with B16 cells and LM cells modified for the expression of MAA and the secretion of IL-2 or IFN-gamma alone (RLBA-IL-2 or RLBA-IFN-gamma cells). Both natural killer/lymphokine-activated killer (NK/LAK) cells and Lyt-2.2 + CTLs with anti-melanoma cytotoxic activities were predominant in mice immunized with the double cytokine-secreting cells. B16 melanoma cells persisted in mice treated with RLBA-IL-2 cells (B16-R3). The B16-R3 cells were resistant to anti-melanoma effector cells from mice immunized with RLBA-IL-2 cells. The recurrent melanoma cells were deficient in the expression of MHC class I determinants. Class I expression by B16-R3 cells was increased if they were incubated in medium conditioned by the growth of IFN-gamma-secreting RLBA-IL-2/IFN-gamma or RLBA-IFN-gamma cells. After incubation, the sensitivity of B16-R3 melanoma cells to immune-effector cells from mice immunized with RLBA-IL-2 cells was restored. The survival of mice bearing low MHC class I-expressing B16-R3 cells, treated RLBA-IL-2/IFN-gamma cells, was determined. The treated animals survived significantly longer than mice with B16-R3 melanoma treated with RLBA-IL-2 cells. Similar results were obtained for mice with B16-R3 melanoma treated with RLBA-IFN-gamma cells. We postulate that immunization of mice with IL-2/IFN-gamma double cytokine-secreting cells stimulated multiple anti-melanoma effector mechanisms. Analogous to the enhanced therapeutic anti-tumour effects of combination chemotherapy, it was likely that treatment with a cellular immunogen engineered to stimulate more than one effector mechanism resulted in the elimination of larger numbers of tumour cells than treatment with an immunogen that stimulated a single effector mechanism alone.

[Effect of the use of human hyperimmune plasma against Pseudomonas protein for protection against Pseudomonas sepsis in burn mice].

A controlled study was performed to evaluate the efficacy of human hyperimmune plasma (HIP) for protecting burned mice from Pseudomonas infection. The HIP was prepared from healthy volunteers immunized with endotoxin protein (Ep) of Pseudomonas aeruginosa. It contained antibody against Ep up to the titre higher than 1:128. Mice with full-thickness burn of 13% TBSA, infected by subeschar injection of 0.2 ml P. aeruginosa (CFU/ml), were treated with HIP at 6 hrs and 18 hrs postburn. The survival rate of the former on the 7th day was 45%, while in mice treated with normal plasma (NP) was 14% and in control mice 10% (P < 0.01). If the HIP was given 18h after burn, the survival rate was 43%, while in mice with NP was 39% and in control 42% (P > 0.05). The results indicate that HIP is able to protect burned mice from Pseudomonas infection giving at 6 hrs postburn (pre sepsis) but not at 18 hrs postburn (post sepsis).

[Ecological changes in burn wound bacterial flora].

A comparative study of the ecology of the burn wound bacterial flora, during Jan. 1970 to Dec. 1971 (Group I) and Jan. 1985 to Dec. 1986 (Group II) was carried out. The incidence of Gram positive cocci was 40.70% in Group I versus 45.66% in Group II. That of Gram negative bacilli was 54.92% and 48.10% respectively. The occurrence of Ps. aeruginosa was markedly reduced, in Group I it reached 35.08% versus 11.26% in Group II (P less than 0.001). The incidence of Enterobacter aerogenes was significantly increased, in Group I it was only 3.69% but it accounted for 11.14% in Group II (P less than 0.001). Before 1972, K. pneumonia and E. cloacae were seldom found on burn wounds, in Group II, however, the incidence was 3.79% and 3.06% respectively. Acinetobacter anitratum occurred more often in Group II than in Group I, being 3.30% and 1.38% respectively (P less than 0.05). A total of 79 strains of Staphylococcus aureus were isolated from burn wounds, during Dec. 1986 to Nov. 1987. Among them Methicillin resistant Staphylococcus aureus (MRSA) accounted for 58 strains (73.4%) that is notable problem. In this centre 1% silver sulphadiazine has been used routinely since 1972 and third-generation cephalosporins have been used widely since 1983, there are the principle causes of the changing pattern of bacterial flora on the burn wounds.