Remote ischemic perconditioning in thrombolysed stroke patients: randomized study of activating endogenous neuroprotection - design and MRI measurements.

BACKGROUND: Intravenous administration of alteplase is the only approved treatment for acute ischemic stroke. Despite the effectiveness of this treatment, 50% of patients suffer chronic neurological disability, which may in part be caused by ischemia-reperfusion injury. Remote ischemic perconditioning, performed as a transient ischemic stimulus by blood-pressure cuff inflation to an extremity, has proven effective in attenuating ischemia-reperfusion injury in animal models of stroke. Remote ischemic perconditioning increases myocardial salvage in patients undergoing acute revascularization for acute myocardial infarction. To clarify whether a similar benefit can be obtained in patients undergoing thrombolysis for acute stroke, we included patients from June 2009 to January 2011. AIM AND DESIGN: The aims of the study are: to estimate the effect of remote ischemic perconditioning as adjunctive therapy to intravenous alteplase of acute ischemic stroke within the 4-h time window and to investigate the feasibility of remote ischemic perconditioning performed during transport to hospital in patients displaying symptoms of acute stroke. Patients are randomized to remote ischemic perconditioning in a single-blinded fashion during transportation to hospital. Only patients with magnetic resonance imaging-proven ischemic stroke, who subsequently are treated with intravenous alteplase, and in selected cases additional endovascular treatment, are finally included in the study. STUDY OUTCOMES: Primary end-point is penumbral salvage. Penumbra is defined as hypoperfused yet viable tissue identified as the mismatch between perfusion-weighted imaging and diffusion-weighted imaging lesion on magnetic resonance imaging scans. Primary outcome is a mismatch volume not progressing to infarction on one-month follow-up T2 fluid attenuated inversion recovery. Secondary end-points include: infarct growth (expansion of the diffusion-weighted imaging lesion) from baseline to the 24-h and one-month follow-up examination. Infarct growth inside and outside the acute perfusion-weighted imaging-diffusion-weighted imaging mismatch zone is quantified by use of coregistration. Clinical outcome after three-months. The influence of physical activity (Physical Activity Scale for the Elderly score) on effect of remote ischemic perconditioning. Feasibility of remote ischemic perconditioning in acute stroke patients. SUMMARY: This phase 3 trial is the first study in patients with acute ischemic stroke to evaluate the effect size of remote ischemic perconditioning as a pretreatment to intravenous alteplase, measured as penumbral salvage on multimodal magnetic resonance imaging and clinical outcome after three-months follow-up.

Localization of white-matter lesions and effect of vascular risk factors in late-onset major depression.

BACKGROUND: Several studies suggest that patients with late-onset major depression (MD) have an increased load of cerebral white-matter lesions (WMLs) compared with age-matched controls. Vascular risk factors such as hypertension and smoking may confound such findings. Our aim was to investigate the association between the localization and load of WMLs in late-onset MD with respect to vascular risk factors. METHOD: We examined 22 consecutive patients with late-onset first-episode MD and 22 age- and gender-matched controls using whole-brain magnetic resonance imaging (MRI). The localization, number and volume of WMLs were compared between patients and controls, while testing the effect of vascular risk factors. RESULTS: Among subjects with one or more WMLs, patients displayed a significantly higher WML density in two white-matter tracts: the left superior longitudinal fasciculus and the right frontal projections of the corpus callosum. These tracts are part of circuitries essential for cognitive and emotional functions. Analyses revealed no significant difference in the total number and volume of WMLs between groups. Patients and controls showed no difference in vascular risk factors, except for smoking. Lesion load was highly correlated with smoking. CONCLUSIONS: Our results indicate that lesion localization rather than lesion load differs between patients with late-onset MD and controls. Increased lesion density in regions associated with cognitive and emotional functions may be crucial in late-onset MD, and vascular risk factors such as smoking may play an important role in the pathophysiology of late-onset MD, consistent with the vascular depression hypothesis.

Risk factors and outcome in ICU-acquired infections.

BACKGROUND: Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU-acquired infections, and potential mortality attributable to such infections. METHODS: An observational study was performed in a 10-bed multidisciplinary ICU. For a period of 27 months, all patients admitted for >or=48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time-varying proportional hazards regression. RESULTS: Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90, Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2-5.4), independent of age and disease severity. CONCLUSIONS: Mortality was increased by ICU-acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro-pulmonary hypothesis of ICU-acquired pneumonia. The proposition that blood transfusions increase the risk of ICU-acquired nosocomial infections was not supported.

On error prediction in circular systematic sampling.

An extended covariogram model is discussed for estimating the precision of circular systematic sampling. The extension is motivated by recent developments in shape analysis of featureless planar objects. Preliminary simulation results indicate that it is important to consider the extended covariogram model.

Endometriosis is not associated with or linked to the GALT gene.

OBJECTIVE: To investigate a possible association between the carrier frequency of the N314D mutation in the galactose-1-phosphate uridyl transferase (GALT) gene and endometriosis and linkage to the short arm of chromosome 9, where the GALT gene resides. DESIGN: Association and linkage study. SETTING: Population material collected for case and family studies in endometriosis. PATIENT(S): Women diagnosed with endometriosis by laparotomy or laparoscopy. INTERVENTION(S): Association with the GALT gene investigated by genotyping 85 affected women and 213 unrelated control women and a scan for linkage to chromosome 9 in 205 women from 64 families with endometriosis. MAIN OUTCOME MEASURE(S): Multipoint parametric lod scores and frequency of alleles. RESULT(S): There was no significant difference in allele frequency for the N314D polymorphism in patients compared with control subjects. No evidence for linkage was found to chromosome 9p, where the GALT gene resides. CONCLUSION(S): The experiments reported herein provide no evidence supporting involvement of the GALT locus in the development of endometriosis.

Perspective: a five-country analysis of the impact of four different Haemophilus influenzae type b conjugates and vaccination strategies in Scandinavia.

Prior to vaccinations against invasive Haemophilus influenzae type b (Hib) diseases in Scandinavia, first initiated in Finland in 1986, the incidence of cases in those five countries was 49/100,000/year in 0- to 4-year-olds and 3.5/100,000 overall. During the following decade, Hib conjugates administered to young children had approximately 95% effectiveness, regardless of which conjugate was used, whether two or three primary doses were administered, and at what age in early infancy the first vaccination was given. The herd immunity effect has extended protection to older age groups. A similar effectiveness of different conjugates in five countries despite considerable diversity in approach suggests that the same impact would occur in other regions with comparable epidemiology. The Scandinavian experience supports the view that three primary vaccine doses are not imperative, thus suggesting that reducing doses of costly Hib vaccines would be one way to facilitate their usage in regions with limited resources.

Immunogenicity of two efficacious outer membrane protein-based serogroup B meningococcal vaccines among young adults in Iceland.

Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.

Comparison of Roche Cobas Amplicor and Abbott LCx for the rapid detection of Chlamydia trachomatis in specimens from high-risk patients.

OBJECTIVE: To evaluate two automated amplification systems for the detection of Chlamydia trachomatis in urogenital specimens, the Cobas Amplicor (Roche Diagnostic Systems, Branchburg, NJ) and the LCx (Abbott Laboratories, Abbott Park, IL). STUDY DESIGN: The two systems were compared testing specimens from 302 high-risk patients, including 98 female cervical swab specimens and 204 male urine specimens. The patients attended the state STD clinic in Reykjavik, Iceland, either because of symptoms or as a result of contract tracing. RESULTS: The prevalence of C. trachomatis infection was 15.3% in women and 13.2% in men. For the male urine specimens, the sensitivity and specificity were 100% and 99.4% for the Cobas Amplicor and 74.1% and 100% for the LCx. In the cervical swabs, both systems detected all 15 true-positive specimens. The internal control used with the Cobas Amplicor detected inhibition in 2% of the male urine and 20% female cervical swabs, respectively. CONCLUSION: The Cobas Amplicor demonstrated slightly better sensitivity than LCx in male urine specimens. Both systems offer the benefits of automation for routine diagnostic testing.

Reduced prevalence of cervical Chlamydia infection among women requesting termination.

BACKGROUND: The prevalence and pattern of Chlamydia trachomatis infection among women requesting induced abortion in the three year period 1992-95 was evaluated and compared to the results of a previous study in 1982-84, where the prevalence of chlamydial infection had been 13.5%. METHODS: A total of 1995 women requested termination, 1855 (93%) of whom were tested for Chlamydia and were included in the study. Two types of tests for chlamydial infection, ELISA and PCR, were used in two consecutive periods. In addition cultures for gonorrhea were done in each case. Information on age, marital status, parity, gestational age and the results of chlamydia and gonorrhea tests of the women and sexual partners were recorded. RESULTS: Chlamydia trachomatis positive women were 149 (8.0%), a significant reduction from the previous 1982-84 study (p<0.001). Women with positive tests were significantly younger (80% < or = 25 years of age; p<0.001) and more frequently single (86.6%; p<0.001), than those with negative tests, as in the previous period. Of the partners, 80.4% were contacted, and 52.1% presented for investigation. Of those tested 42.1% were Chlamydia positive. Four women (0.2%) had Neisseria gonorrhea but none of the partners. CONCLUSIONS: The prevalence of Chlamydia trachomatis is receding among women coming for termination of pregnancy. As treatment before or at operation has repeatedly been shown to be of benefit and since the prevalence is still considerable, continued screening of these women is justified.

Acute bacterial meningitis in adults. A 20-year overview.

BACKGROUND: Most clinical overviews of acute bacterial meningitis have either focused on children or all age groups combined, although the disease poses serious problems in the adult population. OBJECTIVE: To study the clinical and microbiological features of adult bacterial meningitis in Iceland, as a representative of the average European or North American community. PATIENTS AND METHODS: Data on a total of 132 cases in 127 patients (age, > or = 16 years) who were diagnosed as having acute bacterial meningitis in Iceland during the years 1975 to 1994 were collected from patient and laboratory records. Complete hospital records were found for 119 of the 132 cases identified. RESULTS: The annual incidence was 1.7/100,000 to 7.2/ 100,000 inhabitants (mean, 3.8/100,000). The most common causative organisms were Neisseria meningitidis (56%), Streptococcus pneumoniae (20%), Listeria monocytogenes (6%), and Haemophilus influenzae (5%). Neisseria meningitidis caused 93% of the infections in the 16- to 20-year-old age group, but it caused only 25% of the infections in patients aged 45 years or older. Listeria monocytogenes caused 14% of these cases. Cases of nosocomial and recurrent meningitis were rare. A significant underlying illness or condition was present in 39% of the patients. The mean mortality was 19.7%, and it did not change during the study period. CONCLUSIONS: In a study that involved all adult patients with bacterial meningitis in a single country for 2 decades, meningococci and pneumococci were the most frequent causative agents. However, meningococci were responsible for only one fourth of the cases among adult patients aged 45 years or older, most of these cases were caused by pneumococci and Listeria. Despite modern medical developments, approximately 20% of adult patients with bacterial meningitis died.

[Immunization against Haemophilus influenzae type b in Iceland. Results after six years use of PRP-D (ProHIBiT(R).].

Haemophilus influenzae type b (Hib) causes meningitis bacteremia and epiglottitis, dangerous infections, which occur mainly in children under five years of age. Incidence of Hib meningitis in that age group in Iceland was 43/100.000 1974-1988. In the fall of 1988 Icelandic health authorities decided to offer infant immunisation against Hib with PRP-D (ProHIBiT(R)) vaccine, product of Connaught Ltd, Canada. Results are presented of this immunisation programme which has been running since spring 1989. The vaccine is administered at the age of three, four, six and 14 months. During the first year of the immunisation programme one dose was offered to children aged 15 months up to end of third year. During the 10 years 1980-1989, 92 children had Hib meningitis, 61 Hib bacteremia or arthritis and 21 acute epiglottitis. During the five years 1990-1994 no child had Hib meningitis or epiglottitis but three had Hib bacteremia. Hib strains were 10-16% of Haemophilus influenzae strains isolated from surface swabs from 0-5 years old children at different periods until spring 1991 but became very scarse after that. Anti-PRP antibodies in blood measured <0.15 u.g/ ml in 20% of children after three doses of vaccine but >1.0j.ig/ml in 95% after four doses. No fully immunized child has had invasive Hib disease, but one had meningitis and two bacteremia after one dose of vaccine and one bacteremia after three doses. In 1993 21 fully immunized three to four years old children received a booster dose of PRP-D. Geometric Mean Titer of anti-PRP was 1.11 jig/ml before and 137.11u.g/ml after the dose. Mean antibodies against diphtheria were 0.37 IU before and 11.69 IU after the dose. It remains uncertain how long anti-PRP will last in vaccinees when Hib strains disappear.

[Human listeriosis diagnosed in Iceland 1978-1994.].

Listeriosis has been recognised in Iceland, as a distinct disease entity in sheep called silage disease (votheysveiki), since 1910. The use of silage was introduced in Iceland in the latter part of the 19th century. Because of the climatic conditions it came into widespread use and the connection between silage and listeriosis was first demonstrated in Iceland by Pálsson et al. The first case of human listeriosis was diagnosed in 1961. The diease was not diagnosed again untill 1978 when four cases were identified. In the period between 1978 and 1994 L. monocytogenes was isolated from 36 patients, 11 males and 25 females. During this period the population of Iceland grew from 224.384 to 264.919. If mother and child are counted as one the incidence is approximately 8.3 per million per year. There were nine cases of neonatal infections, nine cases involving pregnant women, 13 cases of immunosuppressed patients and five patients were previously healthy. There were four miscarriages. The patients received conventional treatment of ampicillin and aminoglycoside or in one case chloramphenicol. All neonates but two survived. One older patient with meningitis died and 3 severely immunocompromised patients died. All of the strains were of the most common serotypes, 4b, l/2a and l/2b. The different serotypes were not evenly distributed during the study period. During the years 1978-1984 only one of 13 isolates was serotype l/2a and the rest was 4b. On the other hand all but three strains isolated since 1985 were either 172a or l/2b. During the first part of the study period the majority of cases involved neonates or pregnant women but during the second part most of the patients were old or immunocompromised. Nothing is known about the source of the infection in any of the patients except in one neonate which was considered to be nosocomially infected.

[Acute bacterial meningitis in adults, a 20 year overview.].

INTRODUCTION: Although acute bacterial meningitis is most common among children, the disease nevertheless poses serious problems in the adult population. However, most clinical overviews of the disease have either focused on children or all age groups combined. SUBJECTS AND METHODS: Information on all patients 5=16 years of age diagnosed in Iceland during the years 1975-1994 was collected from patient records from 10 hospitals and the records of the Dept. of Microbiology at the University Hospital which processes all bacterial isolates from the CSF identified in the country. RESULTS: One hundred thirty six patients were identified, but complete records were found for 123 patients. Yearly incidence ranged from 1.7-7.2/100,000 inhabitants with a mean of 3.8/100,000. The most common causative organisms were Neisseria meningitidis (54%), Streptococcus pneumoniae (20%), Listeria monocytogenes (6%) and Haemophilus influenzae (5%). The relative incidence of N. meningitidis was dependent on age, the organism caused 93% of infections in the 16-20 year age group, whereas only 25% of infections in subjects 3=45 years of age were due to meningococci. On the other hand, the relative incidence of S. pneumoniae did increase from 2% in the younger age group to 37% in the older subjects. L. monocytogenes caused 14% of cases among patients 3=45 years of age. The mean mortality was 19.1% and did not change significantly during the study period. A significant underlying illness or condition was present in 39% of the patients. During the first third of the study period penicillin or ampicillin alone or in combination with chloramphenicol were used as initial empiric therapy in 76% of cases, wheras during the last third of the period these agents were used initially in 24% of patients. The third generation cephalosporins either alone or in combination were instead employed for empiric treatment in almost two-thirds of the patients. CONCLUSIONS: Meningococci were the most common cause of bacterial meningitis in adults in Iceland during the study period, albeit age dependent, and causing only a fourth of infections in patients 3=45 years of age. Mortality did not change during the period. The third generation cephalosporins are now the most commonly used agents for empiric therapy.

[Lower genital tract infection with chlamydia trachomatis in women requesting induced abortion.].

Postoperative pelvic infection is a serious complication of induced abortion, and may occur in 2-6% of cases. A study of the prevalence and distribution by age and marital status of cervical Chlamydia infection in 1991-93 in women seeking termination of pregnancy is in progress. The data for 1993 are presented and compared to results from a previous study. There were 686 women requesting termination of pregnancy in 1993. Of those 636 had induced abortion by suction evacuation, 11 aborted spontaneously, three were not pregnant, two were refused termination of pregnancy and 34 women withdrew their request. Of those who had the operation, 633 (92.3%) had samples taken and 48 were Chlamydia trachomatis positive (7.6%). The reduction from the previous study was significant where 13.5% of the women were Chlamydia positive. The Chlamydia positive women were also younger and more often single than those who were negative. It has been shown that if Chlamydia positive women are treated the incidence of later endometritis and salpingitis is not higher than among those that are negative. This emphasizes the importance of screening and treating Chlamydia positive women requesting termination of pregnancy.

Life-threatening Haemophilus influenzae infections in Scandinavia: a five-country analysis of the incidence and the main clinical and bacteriologic characteristics.

The five countries of Scandinavia (Denmark, Finland, Iceland, Norway, and Sweden) comprise 22.6 million inhabitants and rather homogeneous socioeconomic conditions. A survey of systemic Haemophilus influenzae diseases over the last decades revealed that the reported incidence of H. influenzae disease is increasing. In recent years, the overall incidence has been 3.5 cases per 100,000 people each year (800 cases annually); in children less than 5 years of age, the annual incidence has been 49 cases per 100,000. Meningitis represents only 52% of all systemic H. influenzae diseases, but lack of reliable data may obscure the importance of other entities. Few strains (less than 5%) are beta-lactamase-positive, and the case fatality rate is 3%. Analysis of seasonal variation shows peaks in June and September-October. If the efficacy of the H. influenzae conjugate vaccines were as high as that of a conjugate vaccine used in Finland during 1986-1987 (approximately 85% efficacy), then at least an 80% reduction in life-threatening H. influenzae infections would be achieved annually by routine immunization before or at the age of 6 months.

[Bacterial meningitis in Iceland]. / Bakteriell meningit i Island 1960-1989.

The article reports on the number of patients in Iceland who in the last 30 years have been diagnosed as having bacterial meningitis, and on changes in the choice of medication during this period. The vaccination of Icelandic children against Haemophilus Influenzae B began in 1989.

Three cases of neonatal meningitis caused by Enterobacter sakazakii in powdered milk.

Three cases of neonatal infection caused by Enterobacter sakazakii are reported from the Department of Neonatal Intensive Care, the National University Hospital, Reykjavík, Iceland. These infections occurred during a 9-month period in 1986 and 1987. Two of the neonates, who were normal at birth, survived but were left with brain damage. The third, who had Down's syndrome and severe cardiac malformations, died. The same organism was also grown from groin and anal swabs from a healthy neonate. E. sakazakii was not isolated from any environmental sources in the neonatal wards or in the milk kitchen, but it was grown from several lots of the powdered-milk formula used in the hospital. The four E. sakazakii strains isolated from the neonates were indistinguishable from 22 strains grown from the formula. Their biotypes, plasmid DNA profiles, and antibiograms were identical.

Blood group, secretor status and susceptibility to bacterial meningitis.

Epidemiological evidence is summarized for associations of ABO blood group and secretor status with susceptibility to invasive disease due to capsulate organisms responsible for the majority of bacterial meningitis. Host-parasite interactions that might underly these findings are proposed and evidence to support or refute them provided.