Methicillin Resistance In Staphylococci : Horizontal Transfer of Mobile Genetic Element (SCCmec) Between Staphylococcal Species

Regardless of the existence of antibiotics, infectious diseases are the leading causes of death in the world. Staphylococci cause many infections of varying severity, although they can also exist peacefully in many parts of the human body. Most often Staphylococcus aureus colonises the nose, and that colonisation is considered to be a risk factor for spread of this bacterium. S. aureus is considered to be the most important Staphylococcus species. It poses a challenge to the field of medicine, and one of the most problematic aspects is the drastic increase of the methicillin-resistant S. aureus (MRSA) strains in hospitals and community world-wide, including Finland. In addition, most of the clinical coagulase-negative staphylococcus (CNS) isolates express resistance to methicillin. Methicillin-resistance in S. aureus is caused by the mecA gene that encodes an extra penicillin-binding protein (PBP) 2a. The mecA gene is found in a mobile genomic island called staphylococcal chromosome cassette mec (SCCmec). The SCCmec consists of the mec gene and cassette chromosome recombinase (ccr)gene complexes. The areas of the SCCmec element outside the ccr and mec complex are known as the junkyard J regions. So far, eight types of SCCmec(SCCmec I- SCCmec VIII) and a number of variants have been described. The SCCmec island is an acquired element in S. aureus. Lately, it appears that CNS might be the storage place of the SCCmec that aid the S. aureus by providing it with the resistant elements. The SCCmec is known to exist only in the staphylococci. The aim of the present study was to investigate the horizontal transfer of SCCmec between the S. aureus and CNS. One specific aim was to study whether or not some methicillin-sensitive S. aureus (MSSA) strains are more inclined to receive the SCCmec than others. This was done by comparing the genetic background of clinical MSSA isolates in the health care facilities of the Helsinki and Uusimaa Hospital District in 2001 to the representatives of the epidemic MRSA (EMRSA) genotypes, which have been encountered in Finland during 1992-2004. Majority of the clinical MSSA strains were related to the EMRSA strains. This finding suggests that horizontal transfer of SCCmec from unknown donor(s) to several MSSA background genotypes has occurred in Finland. The molecular characteristics of representative clinical methicillin-resistant S. epidermidis (MRSE) isolates recovered in Finnish hospitals between 1990 and 1998 were also studied, examining their genetic relation to each other and to the internationally recognised MRSE clones as well, so as to ascertain the common traits between the SCCmec elements in MRSE and MRSA. The clinical MRSE strains were genetically related to each other; eleven PFGE types were associated with sequence type ST2 that has been identified world-wide. A single MRSE strain may possess two SCCmec types III and IV, which were recognised among the MRSA strains. Moreover, six months after the onset of an outbreak of MRSA possessing a SCCmec type V in a long-term care facility in Northern Finland (LTCF) in 2003, the SCCmec element of nasally carried methicillin-resistant staphylococci was studied. Among the residents of a LTCF, nasal carriage of MR-CNS was common with extreme diversity of SCCmec types. MRSE was the most prevalent CNS species. Horizontal transfer of SCCmec elements is speculated to be based on the sharing of SCCmec type V between MRSA and MRSE in the same person. Additionally, the SCCmec element of the clinical human S. sciuri isolates was studied. Some of the SCCmec regions were present in S. sciuri and the pls gene was common in it. This finding supports the hypothesis of genetic exchange happening between staphylococcal species. Evaluation of the epidemiology of methicillin-resistant staphylococcal colonisation is necessary in order to understand the apparent emergence of these strains and to develop appropriate control strategies. SCCmec typing is essential for understanding the emergence of MRSA strains from CNS, considering that the MR-CNS may represent the gene pool for the continuous creation of new SCCmec types from which MRSA might originate.

Injection laryngoplasty with autologous fascia for treatment of unilateral vocal fold paralysis

The purpose of this dissertation was to study the applicability of minced autologous fascia graft for injection laryngoplasty of unilateral vocal fold paralysis (UVFP). Permanence of augmentation and host versus graft tissue reactions were of special interest. The topic deals with phonosurgery, which is a subdivision of the Ear, Nose and Throat-speciality of medicine. UVFP results from an injury to the recurrent or the vagal nerve. The main symptom is a hoarse and weak voice. Surgery is warranted for patients in whom spontaneous reinnervation and a course of voice therapy fails to improve the voice. Injection laryngoplasty is a widespread surgical technique which aims to restore glottic closure by augmenting the atrophied vocal muscle, and also by turning the paralyzed vocal fold towards midline. Currently, there exists a great diversity of synthetic, xenologous, homologous, and autologous substances available for injection. An autologous graft is perfect in terms of biocompatibility. Free fascia grafts have been successfully used in the head and neck surgery for decades, but fascia had not been previously applied into the vocal fold. The fascia is harvested from the lateral thigh under local anesthesia and minced into paste by scissors. Injection of the vocal fold is performed in laryngomicroscopy under general anesthesia. Three series of clinical trials of injection laryngoplasty with autologous fascia (ILAF) for patients with UVFP were conducted at the Department of Otorhinolaryngology of the Helsinki University Central Hospital. The follow-up ranged from a few months to ten years. The aim was to document the vocal results and possible morbidity related to graft harvesting and vocal fold injection. To address the tissue reactions and the degree of reabsoprtion of the graft, an animal study with a follow-up ranging from 3 days to 12 months was performed at the National Laboratory Animal Center, University of Kuopio. Harvesting of the graft and injection was met with minor morbidity. Histological analysis of the vocal fold tissue showed that fascia was well tolerated. Although some resorption or compaction of the graft during the first months is evident, graft volume is maintained well. When injected deep and laterally into the vocalis muscle, the fascia graft allows normal vibration of the vocal fold mucosa to occur during phonation. Improvement of voice quality was seen in all series by multiple objective parameters of voice evaluation. However, the vocal results were poor in cases where the nerve trauma was severe, such as UVFP after chest surgery. ILAF is most suitable for correction of mild to moderate glottic gaps related to less severe nerve damage. Our results indicate that autologous fascia is a feasible and safe new injection material with good and stable vocal results. It offers a practical solution for surgeons who treat this complex issue.

Vertigo in children

Vertigo in children is more common than previously thought. However, only a small fraction of affected children meet a physician. The reason for this may be the benign course of vertigo in children. Most childhood vertigo is self-limiting, and the provoking factor can often be identified. The differential diagnostic process in children with vertigo is extensive and quite challenging even for otologists and child neurologists, who are the key persons involved in treating vertiginous children. The cause of vertigo can vary from orthostatic hypotension to a brain tumor, and thus, a structured approach is essential in avoiding unnecessary examinations and achieving a diagnosis. Common forms of vertigo in children are otitis media-related dizziness, benign paroxysmal vertigo of childhood, migraine-associated dizziness, and vestibular neuronitis. Orthostatic hypotension, which is not a true vertigo, is the predominant type of dizziness in children. Vertigo is often divided according to origin into peripheral and central types. An otologist is familiar with peripheral causes, while a neurologist treats central causes. Close cooperation between different specialists is essential. Sometimes consultation with a psy-chiatrist or an ophthalmologist can lead to the correct diagnosis. The purpose of this study was to evaluate the prevalence and clinical characteristics of vertigo in children. We prospectively collected general population-based data from three schools and one child wel-fare clinic located close to Helsinki University Central Hospital (HUCH). A simple questionnaire with mostly closed questions was given to 300 consecutive children visiting the welfare clinic. At the schools, entire classes that fit the desired age groups received the questionnaire. Of the 1050 children who received the questionnaire, 938 (473 girls, 465 boys) returned it, the response rate thus being 89% (I). In Study II, we evaluated the 24 vertiginous children (15 girls, 9 boys) with true vertigo and 12 healthy age- and gender-matched controls. A detailed medical history was obtained using a structured approach, and an otoneurologic examination, including audiogram, electronystagmography, and tympanometry, was performed at the HUCH ear, nose, and throat clinic for cooperative subjects. In Study III, we reviewed and evaluated the medical records of 119 children (63 girls, 56 boys) aged 0-17 years who had visited the ear, nose, and throat clinic with a primary complaint of vertigo in 2000-2004. We also wanted information about indications for imaging of the head in vertiginous children. To this end, we reviewed the medical records of 978 children who had undergone imaging of the head for various indications. Of these, 87 children aged 0-16 years were imaged because of vertigo. Subjects of interest were the 23 vertiginous children with an acute deviant finding in magnetic resonance images or com-puterized tomography (IV). Our results indicate that vertigo and other balance problems in children are quite common. Of the HUCH area population, 8% of the children had sometimes experienced vertigo, dizziness, or balance problems. Of these 23% had vertigo sufficiently severe to stop their activity (I). The structured data collection approach eased the evaluation of vertiginous children. More headaches and head traumas were observed in vertiginous children than in healthy controls (II). The most common diagnoses of ear, nose, and throat clinic patients within the five-year period were benign paroxysmal vertigo of child-hood, migraine-associated dizziness, vestibular neuronitis, and otitis media-related vertigo. Valuable diagnostic tools in the diagnostic process were patient history and otoneurologic examinations, includ-ing audiogram, electronystagmography, and tympanometry (III). If the vertiginous child had neurologi-cal deficits, persistent headache, or preceding head trauma, imaging of the head was indicated (IV).

Wegener's granulomatosis in Finland in 1981-2000

Objectives: Wegener s granulomatosis (WG) is a vasculitis with a predilection for the airways and kidneys. An increasing incidence and improved prognosis of WG has been shown. The aim of this study was to evaluate the incidence, clinical presentation, diagnostic delay, risk of dialysis-dependent renal insufficiency and mortality of WG in 1981-2000. Patients and methods: Data was retrieved from the Finnish hospital discharge register and hospital case reports. Patients diagnosed with WG in 1981-2000 were included, and their demographic and clinical data recorded. The patients were crossed with the national kidney dialysis register and the national mortality statistics. Results: A total of 492 patients (243 ♂ , 249 ♀) were diagnosed at a mean age of 54 years (SD 18). The incidence increased from 1.9 to 9.3/ million/ year. The median diagnostic delay decreased from 17 to 4 months. Patients presented most often with symptoms of the ear, nose and throat (ENT) (45%), lung (36%), musculoskeletal system (22%) and kidney (11%). Initial lung involvement, constitutional symptoms, high erythrocyte sedimentation rate (ESR) and high ELK scores [(number of simultaneously involved organ groups (ENT, Lung, Kidney)] were associated with a shorter diagnostic delay. Medical treatment of WG patients remained similar in the 1980s and 1990s. Almost 90% of patients received cyclophosphamide (CYC) and more than 90% glucocorticoid medication at some point during the course of the disease. Eighty-four patients (17%) needed dialysis. Initial renal involvement and elevated serum creatinine values were related to an increased risk of dialysis-dependent kidney disease. In two-thirds of the patients, renal impairment was reversible. Dialysis became chronic (>3 months) in 32 patients (6.5%). Nineteen patients (3.9%) received a kidney transplant. Altogether 203 patients (99 men, 104 women) died before 30 June 2005. WG was the underlying cause of death in 37%. The crude one-year and five-year survival rates were 83.3% and 74.2%, respectively. The standardized mortality ratio was 3.43 (95% CI = 2.98 to 3.94). Older age and elevated creatinine level at diagnosis predicted shorter survival. ENT symptoms at presentation and treatment with CYC were associated with better outcome. There was no additional risk associated with male gender or with either of the decades (1981-1990 and 1991-2000) Conclusions: In 1981-2000, the incidence of WG increased ca. 4.5-fold and diagnostic delay decreased to ca. one-fourth, reflecting increased recognition of the disease and improved diagnostic means. WG patients are at great risk of developing dialysis-dependent renal insufficiency and an increased risk of dying. During the study period the treatment of WG did not change markedly, nor did the prognosis improve.

Snoring and sleep apnea in children

Snoring is a primary and major clinical symptom of upper airway obstruction during sleep. Sleep-disordered breathing ranges from primary snoring to significant partial upper airway obstruction, and obstructive sleep apnea. Adult snoring and obstructive sleep apnea have been extensively studied, whereas less is known about these disorders in children. Snoring and more severe obstructive sleep apnea have been shown to have a harmful effect on the neurobehavioral development of children, but the mechanisms of this effect remains unknown. Furthermore, the correlation of this effect to objective sleep study parameters remains poor. This study evaluated the prevalence of snoring in preschool-aged children in Finland. Host and environmental risk factors, and neurobehavioral and neurocognitive symptoms of children suffering from snoring or obstructive sleep apnea were also investigated. The feasibility of acoustic rhinometry in young children was assessed. The prevalence and risk factors of snoring (I) were evaluated by a questionnaire. The random sample included 2100 children aged 1-6 years living in Helsinki. All 3- to 6-year-old children whose parents reported their child to snore always, often, or sometimes were categorized as snorers, and invited to participate to the clinical study (II-IV). Non-snoring children whose parents were willing to participate in the clinical study were invited to serve as controls. Children underwent a clinical ear-nose-throat examination. Emotional, behavioral, and cognitive performances were evaluated by Child Behavioral Checklist (CBCL), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) and NEPSY-A Developmental Neuropsychological Assessment (NEPSY). Nasal volume was measured by acoustic rhinometry, and nasal resistance by rhinomanometry. Lateral and posteroanterior cephalometry were performed. A standard overnight ambulatory polysomnography was performed in the home environment. Twenty-six healthy children were tested in order to assess the feasibility of acoustic rhinometry in young children (V). Snoring was common in children; 6.3% of children snored always or often, whereas 81.3% snored never or occasionally. No differences were apparent between snorers and non-snorers regarding age, or gender. Pediatric snoring was associated with recurrent upper respiratory infections, otitis media, and allergic rhinitis. Exposure to parental tobacco smoke, especially maternal smoking, was more common among snorers. Rhinitis was more common among children who exposured to tobacco smoke. Overnight polysomnography (PSG) was performed on 87 children; 74% showed no signs of significant upper airway obstruction during sleep. Three children had obstructive apnea/hypopnea index (OAHI) greater than 5/h. Age, gender, or a previous adenoidectomy or tonsillectomy did not correlate with OAHI, whereas tonsillar size did correlate with OAHI. Relative body weight and obesity correlated with none of the PSG parameters. In cephalometry, no clear differences or correlations were found in PSG parameters or between snorers and non-snorers. No correlations were observed between acoustic rhinometry, rhinomanometry, and PSG parameters. Psychiatric symptoms were more frequent in the snoring group than in the nonsnoring group. In particular, anxious and depressed symptoms were more prevalent in the snoring group. Snoring children frequently scored lower in language functions. However, PSG parameters correlated poorly with neurocognitive test results in these children. This study and previous studies indicate that snoring without episodes of obstructive apnea or SpO2 desaturations may cause impairment in behavioral and neurocognitive functions. The mechanism of action remains unknown. Exposure to parental tobacco smoke is more common among snorers than non-snorers, emphasizing the importance of a smoke-free environment. Children tolerated acoustic rhinometry measurements well.

Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.