A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects.

BACKGROUND: Effective planning and preparedness against a possible future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adjuvanted vaccine formulations of relatively lower antigen content. AIM: This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 µ) [DOSAGE ERROR CORRECTED] A/H5N1 pre-pandemic vaccine compared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. METHODS: A total of 722 subjects were randomized in equal numbers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the administration of each vaccine dose by hemagglutination inhibition (HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. RESULTS: The low-dose vaccine was demonstrated to be non-inferior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two criteria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. CONCLUSION: These data demonstrate that a low antigen dose in combination with MF59 adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects.

Nodular fasciitis of the external auditory canal.

PROBLEM: Nodular fasciitis (NF) is a reactive myofibroblastic proliferation that may be misdiagnosed as a sarcoma because of its rapid growth, rich cellularity, and mitotic activity. NF is uncommon in the auricular region. We describe a case of nodular fasciitis of the external auditory canal in an 8-year-old male. METHODOLOGY: An excisional biopsy was performed, and the pathologic examination was consistent with nodular fasciitis; however, the lesion recurred within a month requiring that a total excision be done. RESULTS: The patient is without recurrence 7 months after the total excision. CONCLUSIONS: Because its histologic features closely mimick a malignant lesion, NF must be considered in the differential diagnosis of a mass originating from the external auditory canal to avoid overly aggressive and functionally debilitating treatment.

A case of Brucella endocarditis in association with superficial femoral artery thrombus.

We report here a case of Brucella endocarditis associated with superficial femoral artery thrombus. The patient was treated only with medical treatment. The clinical significance of the case was the presence of two rare complications of brucellosis:endocarditis and arterial thrombus.

Extended-spectrum beta-lactamases in ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae isolates in Turkish hospitals.

PURPOSE: To study the prevalence of TEM-, SHV- and GES-type beta -lactamases among Escherichia coli and Klebsiella pneumoniae strains having ceftazidime MICs higher than 2 mg/L. METHODS: A total of 63 E. coli and 41 K. pneumoniae isolated from five different university hospitals were studied for the existence of TEM-, SHV- and GES-type beta -lactamases. Susceptibility tests were carried out according to the criteria of National Committee for Clinical Laboratory Standards. MICs were obtained by agar dilution method. Existence of extended-spectrum beta -lactamases (ESBLs) were assessed by double-disc synergy test (DDST). Existence of the above-mentioned beta -lactamase genes were studied both by PCR with specific oligonucleotide primers and isoelectric focusing methods. RESULTS: None of the isolates were carbapenem-resistant. DDSTs were positive in 50 (79.3%) and 33 (80.5%) of E. coli and K. pneumoniae , respectively. TEM gene was detected in 41 (65.1%) and 19 (46.3%), whereas SHV gene in 18 (28.6%) and 20 (48.8%) of E. coli and K. pneumoniae strains, respectively. GES genes were not detected. CONCLUSIONS: TEM and SHV genes are highly prevalent among ESBL-producing E. coli and K. pneumoniae , whereas GES-type ESBLs are absent and found not to be responsible of ceftazidime resistance in Turkish hospitals.

An unusual cause of central retinal artery occlusion: acquired immunodeficiency syndrome.

PURPOSE: In patients with acquired immunodeficiency syndrome (AIDS), disturbances in the circulation of retinal vessels are mostly encountered at the microvascular level. Rarely observed large retinal vessel occlusions frequently affect retinal veins. METHODS: A 32-year-old woman was admitted to the authors' clinic with sudden loss of vision. Her clinical and ophthalmologic examinations and laboratory tests were carried out and the results were evaluated. RESULTS: The patient's history revealed a diagnosis of AIDS established 5 years ago. Her corrected visual acuity was limited to light perception in the right eye and 20/60 in the left eye. There was afferent pupillary defect in the right eye. Posterior segment examination demonstrated central retinal artery occlusion in the right eye and cotton-wool spots in the left eye. The clinical examination and laboratory test results did not reveal any comorbid disease state that can contribute to this presentation. CONCLUSIONS: As thrombi may develop in patients with human immunodeficiency virus infection, they should be closely followed up for the development of vasoocclusive disease.

Effect of education on the rate of and the understanding of risk factors for intravascular catheter-related infections.

OBJECTIVE: Intravascular catheters are indispensable tools in modern medical therapy. In spite of their great benefits, however, the widespread use of catheters leads to several complications, including infections that cause significant morbidity, mortality, and economic losses for hospitalized patients. DESIGN: This study was conducted at Farabi Hospital, a 495-bed facility at Karadeniz Technical University Medical School in Trabzon, Turkey, and involved 3 separate periods: preeducation, education, and posteducation. Patients with intravascular catheters were monitored daily, as were the results of their physical examinations. The information acquired was recorded in a questionnaire. RESULTS: During the preeducation period (October 2003 through March 2004), 405 intravascular catheters inserted into 241 patients were observed for 5,445 catheter-days. Seventy-one cases of intravascular catheter-related infection (CRI) were identified, giving a CRI rate of 13.04 infections per 1,000 catheter-days. The catheter-related bloodstream infection (CRBSI) rate was 8.3 infections per 1,000 catheter-days, and the exit-site infection (ESI) rate was 3.5 infections per 1,000 catheter-days. During the posteducation period (June through November 2004), 365 intravascular catheters inserted into 193 patients were observed for 5,940 catheter-days. Forty-five cases of CRI were identified, giving a rate of 7.6 infections per 1,000 catheter-days. The CRBSI rate was 4.7 infections per 1,000 catheter-days, and the ESI rate was 2.2 infections per 1,000 catheter-days. When findings from the 2 periods were compared, it was determined that education reduced CRI incidence by 41.7%. CONCLUSION: CRI can be prevented when hospital personnel are well informed about these infections. We compared the knowledge levels of the relevant personnel in our hospital before and after theoretical and practical training and identified a significant increase in knowledge after training (P<.0001). Parallel to this, although still below ideal levels, we identified a significant improvement in the incidence of CRI during the posteducation period (P=.004). The rate was low for the first 3 months of this period but increased 2.08 times after the third month. In conclusion, regular training for the residents in charge of inserting intravascular catheters and the nurses and interns who maintain the catheters is highly effective in reducing the rate of CRI in large teaching hospitals.

A novel locus for autosomal recessive nonsyndromic hearing impairment, DFNB63, maps to chromosome 11q13.2-q13.4.

Hereditary hearing impairment is a genetically heterogeneous disorder. To date, 49 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been described, and there are more than 16 additional loci announced. In 25 of the known loci, causative genes have been identified. A genome scan and fine mapping revealed a novel locus for ARNSHI (DFNB63) on chromosome 11q13.2-q13.4 in a five-generation Turkish family (TR57). The homozygous linkage interval is flanked by the markers D11S1337 and D11S2371 and spans a 5.3-Mb interval. A maximum two-point log of odds score of 6.27 at a recombination fraction of theta = 0.0 was calculated for the marker D11S4139. DFNB63 represents the eighth ARNSHI locus mapped to chromosome 11, and about 3.33 Mb separate the DFNB63 region from MYO7A (DFNB2/DFNB11). Sequencing of coding regions and exon-intron boundaries of 13 candidate genes, namely SHANK2, CTTN, TPCN2, FGF3, FGF4, FGF19, FCHSD2, PHR1, TMEM16A, RAB6A, MYEOV, P2RY2 and KIAA0280, in genomic DNA from an affected individual of family TR57 revealed no disease-causing mutations.

[Antimicrobial susceptibility and serotype distribution of pneumococci strains isolated from meningitis patients]. / Menenjitli hastalardan izole edilen pnömokoklarin serotip dagilimi ve antibiyotiklere duyarliliklari.

Treatment of life threatening pneumococcal infections such as meningitis has recently become problematic due to the emergence of antibiotic resistant strains. Antimicrobial susceptibility data usually derived from the studies that included all clinical pneumococcal isolates. However, resistance patterns of this microorganism isolated from meningitis cases in our country are not exactly known. The aim of this study was to determine the antimicrobial susceptibility and serotypes of Streptococcus pneumoniae strains isolated from meningitis cases. This retrospective study was designed in three university hospitals in Turkey and 72 pneumococci isolated from patients with meningitis were evaluated. In this study disk diffusion test and E-test methods were used to determine the susceptibility of pneumococci to some antibiotics. All S. pneumoniae isolates were serotyped using Quellung reaction. Although resistance for oxacillin was found by disc diffusion method in 11 isolates, only six of them were found to be resistant by E-test. By the latter procedure, no resistance was recorded against ceftriaxone and meropenem, while chloramphenicol resistance was found as 1.4%. In our study, erythromycin, ciprofloxacin and levofloxacin resistance were 2.8%, TMP-SMX resistance was 26.4%, while no vancomycin resistance was detected by disk diffusion. In evaluation of 72 pneumococci, we found 16 different serotypes and four isolates could not be serotyped. The serogroup 23 (n: 19) was the most common one followed by serotype 19 (n: 9) and serotype 14 (n: 7). Of six resistant isolates, three pneumococci were serogroup 23 and the remaining were from three different serotype/serogroups 11, 14 and 19. As a result penicillin resistance in pneumococci isolated from meningitis was low and there was no resistance to ceftriaxone. It seems that ceftriaxone is an appropriate choice for empirical treatment of meningitis in our patients. These findings also revealed that pneumococcal polysaccharide capsule vaccines in use cover most of the invasive pneumococcal serotypes.

Malignant fibrous histiocytoma of the mandible.

We report a case of malignant fibrous histiocytoma (MFH) primary within the mandible of a 32-year-old female. The mandible is a rare location of MFH, accounting for only 3% of all tumours of this type occurring within bone. The clinical, pathological and radiographic features are discussed with special emphasis on the radiographic features of this lesion.

A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.

Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.

Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss.

Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey, 65 unrelated families without mutations in the protein coding region of the GJB2 (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage analysis in one of these families revealed a 13.2 cM critical region between D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region. Homozygosity screening with intragenic markers for TMC1 in the remaining 64 families suggested involvement of this gene in three additional families. Subsequent sequencing of TMC1 in these four families revealed four novel homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative Turkish families from the northeast and east of Turkey.

[Nosocomial Stenotrophomonas maltophilia infections in a university hospital]. / Bir universite hastanesinde nozokomiyal stenotrophomonas maltophilia enfeksiyonlari.

Stenotrophomonas maltophilia is a nosocomial pathogen of increasing importance. In our study, 190 S. maltophilia strains isolated from 153 hospitalized patients between January 2000-April 2004, at Farabi Hospital at Medical School of Karadeniz Technical University, were prospectively evaluated. Of these patients 67.9% were clinically compatible with nosocomial infection, and 32% were considered as colonization. It was observed that rate of infection had a tendency to increase one year of age and above 50 years of age. Nosocomial infection and/ or colonization with S. maltophilia was detected in 19.7 +/- 15.2 (1-89) days after hospitalization. The clinical manifestations were bacteremia (36.5%), pneumoniae (28.8%), urinary system infection (12.5%), surgical site infection (11.5%) and peritonitis (6.7%). The bacteremia episodes were associated with central venous catheter in 37.3% (19/51), ventilator associated pneumonia in 11.7% (6/51), urinary system infection in 7.8% (4/51), peritonitis in 3.9% (2/51), and surgical site infection in 1.9% (1/51) of cases. Nineteen patients (37.3%) had no apparent primary source of infection. Higher APACHE II score, longer duration of hospitalization and prior extended-spectrum antibiotic therapy were observed in most of the patients. Antibiotic susceptibility testing revealed that, the most effective antibiotics against the isolates were trimethoprim-sulfamethoxazole (94%), ticarcillin/clavulanate (79%) and ciprofloxacin (53.5%). Crude mortality rate in the patients with S. maltophilia infections was found to be 25%. In addition, it was observed that proper antibiotic treatment had protective role against mortality (14.6% vs 63.6%; OR = 0.1, Cl95 0.12-0.42, P = 0.000). It can be concluded that to prevent infections due to S. maltophilia , effective infection control programmes and rational antibiotic use policies should be established promptly.

A case of Lemierre's syndrome following Epstein-Barr virus infection.

Lemierre's syndrome, or necrobacillosis, is a life-threatening septic thrombophlebitis of the internal jugular vein. The causative organism is Fusobacterium necrophorum. Here we report a case of Lemierre's syndrome in a young male and describe the clinical presentations and treatment. Epstein-Barr virus (EBV) was a suspected predisposing factor in this case.

Multifocal intradiploic cavernous hemangioma of the skull associated with nasal osteoma.

OBJECTIVE: To present a 42-year-old female patient with multifocal cavernous hemangioma of the skull associated with nasal osteoma. DESIGN: A case report. INTERVENTION METHODS: X-rays, computerized tomography, magnetic resonance imaging, and histopathology were used to achieve the diagnosis of this rare entity. The multiple cavernous hemangiomas were resected en-bloc and a curettage biopsy was obtained from the nasal osteoma. RESULTS: The patient healed well after the operation. No recurrences of the cavernous hemangiomas were observed after one-year follow-up. CONCLUSION: Multifocal cavernous hemangiomas are rare benign lesions of the calvarium, arising from the intrinsic vasculature of the bone. Although they are benign, radiological findings are not always characteristic and their multiple presentation may easily make surgeons consider the other malignancies of the skull in the differential diagnosis. Histopathologic confirmation of the tumor is the definitive method for diagnosis. The treatment of choice is early en bloc resection of the tumour where it is possible.

Endocarditis caused by Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is frequently isolated from hospital environments. In recent years, it has been reported that this bacterium is causing hospital infections at increasing rates and is gaining importance because of its multiple resistance. Although it has been related to several infections, endocarditis caused by S. maltophilia is rarely encountered. In this case study, endocarditis in a 40-y-old man with a history of aortic valve replacement is presented. Blood cultures revealed S. maltophilia to be the aetiological agent, which showed multiresistance to various antibiotics. Ticarcillin-clavulanate and trimethoprim-sulfamethoxazole were used in the treatment.

Melkersson-Rosenthal syndrome: report of three cases.

Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue. It is far more uncommon to find the complete triad since it generally presents in oligosymptomatic forms. We present three cases of the Melkersson-Rosenthal syndrome with the classic triad of symptoms and discuss the etiology and the clinical and electromyography findings of this syndrome.

Myringoplasty in children: factors influencing surgical outcome.

Age, size, and site of perforation, condition of the ear, status of the contralateral ear, grafting materials, and more are considered factors influencing the success rates in myringoplasties in children. The ambivalence in results is mainly due to nonhomogeneous patient groups. In an effort to compose groups as homogeneous as possible for analysis of influencing factors, a retrospective study of 51 pediatric myringoplasty cases (51 ears) was undertaken. All patients had perforations caused by simple chronic otitis media. The overall surgical success rate was 82.3% at 18 months, and for young (5 to 10 years) and older (11 to 16 years) children it was 77.2% and 86.2%, respectively. Anterior, central, and total perforations healed without significant differences. Outcome in unilateral perforations was better than bilateral: 96.9% and 55%, respectively (p < 0.01). Discharging ears (100%) healed better compared with dry ears (75%) (p < 0.05). Analysis of the literature also revealed significant difference in success rates of discharging and dry ears: 92.5% and 80.6%, respectively (p < 0.01). We conclude that, contrary to comments in the literature, discharging ears in children favor good outcome and they should be operated on regardless of age and site of perforation. However, in bilateral perforations results may not be so rewarding.

Morphometric evaluation of the infralabyrinthine approach to the internal auditory canal.

Morphometric evaluation of the infralabyrinthine approach to the internal auditory canal (IAC) was performed using 20 fresh human temporal bones in order to assess the exposure limitations, inherent risks and technical difficulties that may arise due to common anatomic variations of this region. While performing the infralabyrinthine approach to the IAC, minor problems such as an anteriorly placed sigmoid sinus were easily managed. However, in 50% of the specimens, this approach was limited due to variations of the jugular bulb, restricting access to the IAC. Sacrificing the endolymphatic duct in these specimens did not significantly improve the surgical access to the eighth nerve. Furthermore, it was noted that this approach puts the facial nerve and cochlea under the risk of inadvertent damage during drilling. The authors conclude that vestibular nerve sectioning using the infralabyrinthine approach may be performed only in few selected cases and extreme care is needed in order not to damage the structures that limit this approach.