Type IVc Research Articles

Type IV SCCmec found in decade old Brazilian MRSA isolates

Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in hospitalized patients. Since its appearance in the 1960s, the SCCmec has evolved throughout the years into 5 different types (I-V), each bearing a different set of genes. Infection with MRSA SCCmec types I, II or III is almost exclusively restricted to hospitalised patients. However, recently, community acquired MRSA (CA-MRSA) infections have been reported with increasing frequency, usually caused by a type IV SCCmec MRSA in nosocomial settings. We studied the prevalence of SCCmec types in 50 nosocomial strains collected from 1995 to 1999. The SCCmec complex type and presence of Panton-Valentine leukocidin (PVL) were determined by PCR. Strains had been previously typed by PFGE and were now typed by MLST. We found that 3 of the isolates studied bore a type IVc SCCmec all having different PFGE and MLST profiles (ST3, ST5 and ST88). All strains bearing a type III SCCmec belonged to MLST ST239 (Brazilian/Iberian clone). Only the strain which presented the ST5 profile bore the pvl gene. The type IVc SCCmec strains presented relatively lower levels of resistance to oxacillin in comparison to the type III SCCmec strains. The pattern of dissemination of the type IV SCCmec remains to be elucidated. The finding of strains carrying a type IV SCCmec in the present study among strains isolated at least 7 years ago indicates that clones bearing a type IV SCCmec have been present in Brazil for quite some time, and must have gone by undetected.

Use of Highly Discriminatory Fingerprinting to Analyze Clusters of Clostridium difficile Infection Cases Due to Epidemic Ribotype 027 Strains

We compared multilocus variable-number tandem-repeat analysis (MLVA) and macrorestriction endonuclease analysis using pulsed-field gel electrophoresis (PFGE) to determine their utility to identify clusters of Clostridium difficile infection (CDI) among 91 isolates of PCR ribotype 027 (NAP1, for North American pulsed-field type 1) from nine hospitals (and 10 general practitioners associated with one institution) in England. We also examined whether mortality in CDI cases was associated with specific MLVA subtypes. PFGE discriminated between ribotype 027 strains at >98% similarity, identifying five pulsovars (I to V) of 1 to 53 isolates. MLVA was markedly more discriminatory, identifying 23 types of 1 to 15 isolates (>71% similarity). PFGE pulsovars I and IV contained 14 and 8 MLVA types, respectively. Twenty-one of twenty-three (91%) of MLVA types were specific to individual PFGE pulsovars. Four CDI clusters were identified in institution A by conventional epidemiological analysis. MLVA typing identified two enlarged and two additional clusters. Thirty of forty-four (68%) patients in institution A with CDI caused by ribotype 027 strains were assigned to seven distinct clusters by a combination of MLVA typing and epidemiological records. Of 33 patients, comprising 14 different MLVA types, nine (27%) died by day 30 (early deaths). Eight of nine (89%) were associated with PFGE type IV C. difficile ribotype 027. Five of nine early deaths were associated with MLVA type 16, which was the dominant type in this cohort (10/33 cases); 4 other distinct MLVA types accounted for the other early deaths. MLVA was far superior to PFGE for analyzing clusters of CDI both within and between institutions. Further study is needed to examine whether subtypes of C. difficile ribotype 027 affect outcome.

Spread of a methicillin-resistant Staphylococcus aureus ST80 strain in the community of the northern Netherlands

Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA) are emerging as a major public health problem. In this study, we describe the distribution of 54 Panton-Valentine leucocidin (PVL)-carrying MRSA isolates in the northern Netherlands between 1998 and 2005, of which 43 (80%) consisted of the European PVL-positive strain multi locus sequence type 80 with staphylococcal cassette chromosome mec type IVc (ST80). Individual cases and small clusters of ST80 predominated in the community (74%), but ST80 was also found in nursing homes (16%) and hospitals (9%). Long-term carriership (months to years) and reinfection of patients with ST80 has probably led to the strain spreading in the community and subsequently to further migration to health care environments.

Delayed drug hypersensitivity reactions – new concepts

Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications for understanding clinical and immunological features of drug hypersensitivity and a model to explain the frequent skin symptoms in drug hypersensitivity is proposed.

P2090 In vitro activity of API-1252, a novel antistaphylococcal agent, against 100 genotypically unique Staphylococcus aureus strains

Staphylococcus aureus has been recognized as an important pathogen associated with inpatients and community infections. Community-acquired methicillin-resistant S. aureus (CA-MRSA) infections commonly present as skin and soft-tissue infections (SSTIs). Treatment often includes incision and drainage with or without adjunctive antibiotics.This study aimed to identify CA-MRSA infections both phenotypically and genotypically, to determine their spectrum of antibiotic resistance, and to establish the best scheme for molecular distinction between hospital-acquired MRSA (HA-MRSA) and CA-MRSA by staphylococcal cassette chromosome mec (SCCmec) typing and detection of Panton Valentine leukocidin (PVL).50 swabs, from skin and soft tissue of infected lesions of outpatients attending the dermatology department of the Medical School, Alexandria University, were collected. Additionally, a nasal swab was taken from every participant.Collection of swabs from the infected skin and soft tissues, followed by laboratory testing to phenotypically and genotypically identify MRSA. Also, nasal swabs were taken from every patient to identify MRSA colonization.Staphylococcus aureus strains were identified in 38 (76%) of the 50 clinical isolates. 18 (47.37%) out of the 38 S. aureus strains were resistant to oxacillin and cefoxitin discs, were penicillin binding protein 2a (PBP2a) producers, and were initially diagnosed as MRSA. All of the 18 strains were definitively diagnosed as MRSA by mecA gene detection using real time PCR, while only six (33.33%) strains were PVL positive. Using the sets of primers of Zhang et al.: nine (50%) out of the 18 CA-MRSA strains were SCCmec type V, and one (5.56%) was SCCmec type IVc. Then, using the set of primers by Oliveira et al., two (25%) out of the eight untypable MRSA strains were found to be SCCmec type IV, and six (75%) remained untypable.CA-MRSA must be considered when treating skin and soft tissue infections, especially in developing countries. Empirical use of agents active against CA-MRSA is warranted for patients presenting with serious SSTIs.

Treatment of Spinal Cord Perimedullary Arteriovenous Fistula: Embolization versus Surgery

To provide the optimal treatment strategy for perimedullary arteriovenous fistula (PMAVF). Nineteen patients with PMAVF (Type IVa in 9 patients, Type IVb in 6, and Type IVc in 4) were treated at Seoul National University Hospital between January 1988 and March 2001. Their mean age was 28 years (range, 6-52 yr), and the male-to-female ratio was 1.7:1. The mean follow-up period was 20 months (range, 2-55 mo). Most patients presented with symptoms of slowly progressive myelopathy (13 patients). On spinal angiography, all but 2 showed fistula at the level of the conus medullaris. The feeder was the anterior spinal artery and/or the posterior spinal artery in 14 patients and the posterior spinal artery in 5. All patients underwent endovascular or surgical treatment. With endovascular treatment (11 patients; IVa, n = 5; IVb, n = 2; IVc, n = 4), complete angiographic obliteration of fistula was performed in 5 and partial obliteration in 4 (IVa, n = 1; IVb, n = 2; IVc, n = 1). Symptomatic improvement or arrest of progression was achieved in 5 of 9 patients with complete or partial occlusion. Embolization failed in two (IVa, n = 1; IVc, n = 1). With surgery (10 patients [IVa, n = 6; IVb, n = 4], including 2 patients with partial or failed embolization), most (9 of 10) were improved or stable. Good results were achieved with surgery for Types IVa and IVb PMAVF located at the level of the conus medullaris. For Type IVc PMAVF, a fistula located on the ventral side of the spinal cord or above the conus medullaris, endovascular treatment might be considered. Because of rapidly evolving endovascular techniques, however, further studies are warranted.

Optical Limiting Properties of Zinc- and Platinum-Based Organometallic Compounds

Optical power limiting is theoretically studied using an approach that combines quantum electronic structure calculations of multiphoton excitations and classical calculations of dynamical wave propagation. We illustrate the capability of such a combined approach by presenting results for a couple of organometallic compounds; basic metal−base porphyrins, vinylphenylamine porhyrin, and the so-called type IVc platinum compound. A comparative analysis of their electronic properties related to nonlinear absorption of electromagnetic radiation and their optical limiting capability has been performed based on dynamical simulations of the nonlinear pulse propagation taking account of resonant as well as off-resonant effects. Several key features and rate-limiting steps in the transmission have been examined in relation to various characteristics of the pulse. It is found that the resonant vs off-resonant conditions, the saturation conditions and the dephasing play critical roles for the nonlinear transmission. The saturation effects are sensitive to the pulse duration, the inter-system crossing rate and the quenching of the higher triplet state. The inter-system crossing rate has to be comparable with the inverse pulse duration in order to boost the stepwise two-photon channel associated with singlet−singlet followed by triplet−triplet transitions. It is illustrated that structure-to-property relations of the rate-limiting steps serve as important criteria for choices of compounds suitable for the application of interest.

Practical procedures for minor injuries: mallet splint

A very common presentation in emergency care, usually with a history of a sudden resisted flexion of the distal interphalangeal (DIP) joint, often from a trivial mechanism of injury. This deformity is due to the interruption of the mechanism by which the extensor tendon maintains extension at the distal interphalangeal joint. The most common cause for this ( type I) is due to a closed tendon injury when the tendon is either avulsed from its insertion into the base of the distal phalanx or detached together with a small fragment of bone. Another type is due to a more serious open injury to the extensor tendon, either by laceration (type II) or by abrasion with loss of tissue substance in the skin, tendon or bone (type III). The last group (type IV) is due to a fracture of the distal phalanx of substantial size either involving the epiphysis (type IV-A) or after hyperflexion (type IV-B) or hyperextension (type IV-C) (Doyle, 1993).

Treatment of intra-articular fractures of distal radius

目的 探讨桡骨远端关节内骨折手术治疗的效果.方法对 12例桡骨远端关节内骨折按通用分类法分类,Ⅲ型 1例,Ⅳ A型 3例,Ⅳ B型 2例,Ⅳ C型 5例,Ⅳ D型 1例, 5例术前行螺旋 CT和三维重建检查.手术治疗的方法:外固定支架,外固定支架加克氏针,掌侧或背侧支持钢板,或支持钢板加克氏针,以及以单纯克氏针固定.结果随访 8～ 20个月,平均 12个月,优 9例,良 2例,优良率为 91.7%.结论桡骨远端的关节内骨折在闭合复位欠佳时,应该考虑手术治疗,螺旋 CT和三维重建技术在术前准备中可提供充分的骨折资料,术式的选择对不同类型的骨折应有所选择.

高齢者における耳科手術の検討

We performed surgery of the middle ear in 157 patients (171 ears) between April 1997 and March 2001. In this study, the clinical features and outcomes of middle ear surgery performed in 11 patients (13 ears) 70 or more years of age were analyzed. The diagnoses in these 11 cases included chronic otitis media (6 ears), otitis media cholesteatoma (6 ears), and otosclerosis (1 ear). The types of surgery were myringoplasty (2 ears); tympanoplasty type I (3 ears), type IIIc (6 ears) and type IVc (1 ear); tympanoplasty without ossiculoplasty (1 ear); and stapes surgery (1 ear). Surgery was successful in improving the hearing in 4 ears. Prevention of discharge was the primary purpose of surgery in 10 ears, and discharge was controlled in 9 ears. There were no complications or adverse events associated with the surgery. Surgery can be selected to improve the QOL of patients even if marked improvement in hearing is not expected.

Delayed drug hypersensitivity reactions.

Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.

３Ｄ−ＣＴが診断に有用であった耳小骨病変の２例

We report two cases of ossicular lesions correctly diagnosed with three-dimensional CT (3D-CT). The first patient was a 28-year-old male, who had hearing loss in the right ear after a sneeze. The other patient was a 50-year-old male complaining of left ear hearing loss after a head injury. Almost normal hearing was obtained after tympanoplasty type IV-c (case 1) and partial stapedectomy (case 2). Both patients underwent operations by transcanal approach.We were able to make exact diagnoses before operation by 3D-CT in both cases, and 3D-CT reconstruction of the operation field was suitable for modeling of the operations. These cases suggest that 3D-CT is useful not only as a method for diagnosing ossicular lesions, but also as a method for preoperative surgical planning.

Porous Texture and Surface Character of Dehydroxylated and Rehydroxylated MCM-41 Mesoporous Silicas—Analysis of Adsorption Isotherms of Nitrogen Gas and Water Vapor

Four samples of MCM-41 mesoporous silicas whose average pore diameters are 2.4, 2.8, 3.2, and 3.6 nm were prepared using sodium orthosilicate and cationic surfactants of [CH3(CH2)nN(CH3)3]X (n=11, 13, 15, 17). These four samples were calcined at 1123 K in vacuo to obtain the dehydroxylated samples, which were further rehydroxylated at 298 K to obtain the rehydroxylated samples. The adsorption isotherms of nitrogen gas (77 K) for the 12 MCM-41 mesoporous silicas are of Type IVc, giving no adsorption hysteresis. On the other hand, the first adsorption isotherms of water vapor (298 K) for the dehydroxylated MCM-41 samples are quite different from those of nitrogen gas, giving the remarkable adsorption hysteresis. The second water isotherms for the rehydroxylated MCM-41 samples are of Type IV, showing slight hysteresis. Using the nitrogen isotherms, the relation between the pore size and carbon chain length of the surfactant has been determined, and the effect of dehydroxylation and rehydroxylation on the porous texture has been examined. Using the first and second water isotherms, the adsorption model of physisorbed waters adsorbed on the surface silanol groups has been proposed. From the pore size distribution curves of nitrogen and water, the presence of constrictions in the cylindrical pores has been predicted.

Outcome From Treatment For Spinal Arteriovenous Malformation

Our knowledge of the outcome from treatment for spinal arteriovenous malformations (AVMs) is limited to a few small, anecdotal series and is thus far from complete. Furthermore, with the recent rapid evolution of our knowledge of AVM pathology, many reported cases are difficult to place in the current classification system. In general, outcome for the four classifications of AVMs are as follows: type I respond well to surgical disconnection of the arteriovenous fistula if treatment is early; type II AVMs are currently best treated by surgery but risks of a poor outcome need to be carefully considered; type III are only rarely treatable; type IVa and IVb are likely to respond well to surgery but our knowledge is limited; and type IVc are likely to fare poorly from surgery but should have a better outcome from endovascular therapy.

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-alpha: histological evaluation by a modified histological activity index scoring system.

The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-alpha were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activity index (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r = 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and peptide of type III procollagen (PIIIP; r = 0.531, P = 0.0004) or type IV collagen 7S domain (type IV-C; r = 0.241, P = 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P = 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-alpha; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-alpha.

Clinical significance of measurement of PIIIP, Laminin P1, Type IV-C and 7S in patients with chronic liver diseases

Clinical significance of measurement of PIIIP, Laminin P1, Type IV-C and 7S in patients with chronic liver diseases

Antimicrobial activity and disk diffusion susceptibility testing of U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807).

Compound U-76,253A (R-3746), the active metabolite sodium salt of the prodrug ester U-76,252 (CS-807), was demonstrated to be active against members of the family Enterobacteriaceae with 82 and 85% of strains inhibited by less than or equal to 2.0 and less than or equal to 4.0 micrograms/ml, respectively. In addition, U-76,253A inhibited all strains of Branhamella catarrhalis, Haemophilus influenzae, pathogenic Neisseria spp., oxacillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and pneumococci at less than or equal to 4.0 micrograms/ml. Pseudomonas spp., Acinetobacter spp., enterococci, and oxacillin-resistant staphylococci were resistant to U-76,253A. This U-76,253A antimicrobial activity and spectrum was generally superior to that of comparison orally administered cephems (cefaclor, cefuroxime, and cefixime) and the amoxicillin-clavulanic acid combination. Tests with beta-lactamase-producing isolates indicated that U-76,253A was bactericidal and that its MICs were only influenced by high inoculum concentrations (10(7) CFU/ml) against type Ia and IVc enzyme-producing strains. Preliminary disk diffusion interpretive zone criteria were calculated for 10- and 30-micrograms U-76,253A disks and several possible susceptible MIC breakpoints. The absolute interpretive agreement between MICs and zone diameters ranged from 87.8 to 95.6%. Final selection of interpretive criteria awaits further U-76,252 pharmacokinetic information.

Beta-lactamase hydrolysis and inhibition studies of the new 1-carbacephem LY163892.

A novel 1-carbacephem, LY163892, was determined to be more stable to plasmid-mediated beta-lactamases than cefaclor. Chromosomal-mediated Type Ia and IVc enzymes destroyed LY163892 at rates ranging from 16 to 93% that of nitrocefin. LY163892 showed minimal ability to inhibit beta-lactamases other than Type Ia (P99).