Breed-specific reference ranges for standard echocardiographic measurements in salukis.

OBJECTIVES: To establish normal reference ranges for standard echocardiographic measurements in Salukis and to examine whether bodyweight, age, gender and heart rate had an influence on the echocardiographic variables. MATERIALS AND METHODS: Seventy-five privately owned healthy purebred Salukis, aged 2 to 10 years were included. Case history was obtained and dogs were examined by physical examination, complete blood cell count, serum biochemistry and echocardiography. Associations between bodyweight, gender, sex and heart rate and echocardiographic variables were examined using multiple linear regression analysis and allometric scaling. Reference values with 95% prediction intervals were calculated from regression equations. RESULTS: Bodyweight was a significant predictor of left ventricular diameters, left ventricular volumes and E-point-to-septal-separation. Associations between bodyweight and the echocardiographic variables were best described by multiple linear regression models, providing bodyweight-based reference values. Age, gender and heart rate had significant effect on some of the echocardiographic variables and were included in the final models. When the equation included heart rate or age, reference values were calculated using mean heart rate value (80 bpm) and median age value (73 months). CLINICAL SIGNIFICANCE: This study provides detailed bodyweight-based echocardiographic values in normal Salukis which can be used as reference values.

Venous collapse regulates intracranial pressure in upright body positions.

Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure, and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (peripherally inserted central catheter line), and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47 ± 10 yr, mean ± SD) in 7 positions, from supine to sitting (0-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP with predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference, -0.03 ± 2.7 mmHg). No difference was found between predicted and measured ICP for any tilt angle ( P values, 0.65-0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic Investigations.

BACKGROUND: In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. OBJECTIVES: To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. ANIMALS: 110 affected and 128 unaffected client-owned Border Terriers. METHODS: A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. RESULTS: One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. CONCLUSIONS AND CLINICAL IMPORTANCE: The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex.

Long-term subarachnoid haemorrhage survivors still die due to cerebrovascular causes.

OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with sympathetic nervous activation and inflammation. SAH could therefore theoretically be a risk factor for development of cardiovascular disease. The aim of this study was to investigate whether long-term (≥1 year) SAH survivors had an increased risk of death due to cardiovascular causes. MATERIAL & METHODS: SAH patients ≥18 years treated at Umeå University Hospital between 1986 and 2006 were eligible for inclusion. Deceased patients were identified in the Swedish population register. Death certificates from long-term SAH survivors and causes of death in the general population were obtained from the National Board of Health and Welfare, Sweden. The prevalence of comorbidities at the time of SAH was compared with the distribution of cardiovascular risk factors in the northern Sweden MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) health survey. Analyses were stratified for age and sex. RESULTS: In the SAH patients, the median year of SAH was 1992 and the median year of death was 2001. The MONICA survey in 1994 and the distribution of deaths in the general population in 2001 were used for comparison. Long-term SAH survivors had, compared to the general population, a significantly increased risk for death due to cerebrovascular disease (P < 0.0001), but not for death due to cardiovascular disease. Hypertension was more common in SAH patients compared to survey participants (P < 0.01). CONCLUSION: Cerebrovascular causes of death were significantly more common in long-term survivors after SAH compared to the general population.

Severe traumatic brain injury management and clinical outcome using the Lund concept.

This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment.

The professional competence profile of Finnish nurses practising in a forensic setting.

Forensic nurses in Finland work in the two state-maintained forensic hospitals. The main function of these hospitals is to perform forensic psychiatric evaluation and provide treatment for two groups of patients: violent offenders found not guilty by reason of insanity, and those too dangerous or difficult to be treated in regional hospitals. Although the forensic nurses work with the most challenging psychiatric patients, they do not have any preparatory special education for the work. This paper describes the development of nurses who participated in a 1-year further education programme that was tailored to them. The nurses experienced that the 1-year education had a significant impact on their overall competence level. They found that their skills for observing, helping, teaching and caring for their patients had increased during the education. Conversely, it was found that the nurses collaborated little with their patients' family members. They were also not familiar with utilizing research findings in improving their care of patients. Forensic nursing is a global and relatively young profession that combines nursing care and juridical processes. There are, however, significant differences in the qualifications of forensic nurses internationally. The aim of the study was to describe the professional competence profile of practising forensic nurses in Finland and to explore the effects of a 1-year further education programme on that competence profile. The data were collected in 2011-2012 using the Nurse Competence Scale comprising seven competence categories, and analysed using the software package SPSS version 19.0 (SPSS, Inc., Armonk, NY, USA). The participants were 19 forensic nurses and their 15 head nurses. The assessed overall scores from both informant groups indicated a high level of competence across the seven categories. The nurses felt that the overall competence level had increased during the education programme. The increase seen by the head nurses was smaller. The less frequent competence items included utilization of research and involvement of family in care. It can be stated that the 1-year further education programme was effective in developing the nurses' competence profile and, in particular, affected their professional self-confidence. It will, however, be essential to strengthen their skills for working with families and their awareness of evidence-based forensic nursing.

Are intracranial pressure wave amplitudes measurable through lumbar puncture?

OBJECTIVE: The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. METHODS: In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45 mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. RESULTS: The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9 mmHg. At the highest ICP, the difference changed to -0.2 mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. CONCLUSIONS: Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L. METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters. RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation. CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.

Predicting improvement after surgery for palmar hyperhidrosis.

OBJECTIVES: Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. MATERIALS AND METHODS: Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. RESULTS: Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. CONCLUSION: Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS.

Disease progression and treatment response of idiopathic epilepsy in Australian Shepherd dogs.

BACKGROUND: Idiopathic epilepsy (IE) in Australian Shepherds (ASs) occurs worldwide but there is a lack of description of the epilepsy syndrome in this breed. The ABCB1-1Δ mutation is more prevalent in ASs than in many other dog breeds. HYPOTHESIS: Australian Shepherds suffer from a poorly controlled IE syndrome with prevailing severe courses. Seizure control and ABCB1-1Δ mutation might be related in this breed. ANIMALS: Fifty ASs diagnosed with IE and 50 unaffected ASs. METHODS: Predominant study design is a longitudinal cohort study. Pedigrees, medical records, seizure, and treatment data of ASs with IE were analyzed descriptively. Sex, color, and the ABCB1-1Δ genotype were compared between case and control groups and ASs with poorly or well-controlled seizures. Differences in survival times were assessed by logrank tests and Cox regression analysis. RESULTS: Idiopathic epilepsy in ASs is dominated by moderate and severe clinical courses with the occurrence of cluster seizures and status epilepticus and a high seizure frequency. Poor seizure control and a high initial seizure frequency (≥10 seizure days/first 6 months) are associated with shorter survival times (P < .05). Poor seizure control, unrelated to the ABCB1(MDR1) genotype, is evident in 56% of epileptic ASs. Pedigree analysis suggests a genetic basis. CONCLUSION AND CLINICAL IMPORTANCE: Frequent severe clinical courses, poor seizure control unrelated to the ABCB1(MDR1) genotype, and a young age at death compromise animal welfare and warrant further genetic studies to unravel the underlaying molecular mechanisms of IE and seizure control in the breed.

Genome-wide analysis of extended pedigrees confirms IL2-IL21 linkage and shows additional regions of interest potentially influencing coeliac disease risk.

Coeliac disease is a chronic inflammatory condition of the small intestine, triggered by dietary exposure to gluten in genetically susceptible individuals. Risk alleles at HLA-DQA1 and HLA-DQB1 are necessary for disease development, but are alone not sufficient for disease onset. We aimed to identify novel loci underlying susceptibility to coeliac disease through the use of extended Finnish and Hungarian families with multiple affected individuals. An initial whole-genome linkage approach yielded several loci that were followed up further using the Immunochip custom array. Loci with a parametric logarithm of odds (LOD) score of >1.3 were identified at 4q, 6p [human leukocyte antigen (HLA) region], 6q, 7p, 17p, 17q and at 22p. The 4q and 6q loci have been identified previously in coeliac disease risk, whereas follow-up analyses indicate that the 17p and 22p loci may be novel risk loci for coeliac disease. These loci harbour previously described risk variants for other autoimmune diseases, but their segregation patterns do not explain the linkage to coeliac disease. We followed up the linkage to the 4q region, containing the previously described interleukin (IL)2 and IL21 genes. The risk variants at 4q in the studied pedigrees are most likely distinct from previously described risk variants, indicating that the observed linkage may be due to rare high-risk variants of still unknown nature. The importance of this locus to coeliac disease risk was further shown by the finding that serum levels of IL21 were elevated in both untreated and treated coeliac patients compared to controls.

Learning from the world of mental health care: nursing students' narratives.

This narrative study describes the substance of nursing students' learning in the area of mental health and their responses to the challenges of working in the psychiatric field. The data consisted of 39 critical incidents written by 20 Finnish second-year nursing students during their 5-week mental health placement. The narrative analysis method was used in the data analysis and the configuration of three consistent learning storylines: self-awareness and self-esteem, the nurse-patient relationship and mental health care methods. The three storylines characterized the essence of the students' learning and their responses to the challenges of the psychiatric field during the placement. The students were actively exposed to complicated care situations and patient encounters in which they had to face their own emotions and test coping skills. It seems that the critical incident technique stimulated students' narrative skills and possibly sensitized them for listening at the stories of their future patients.

Severe traumatic brain injury: consequences of early adverse events.

BACKGROUND: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre-hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end-tidal carbon dioxide (ETCO(2)). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre. METHODS: Prospective, observational study design. Patients with severe TBI (n = 48), admitted to Umeå University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated. RESULTS: A pre-hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO(2) <4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1-3). CONCLUSION: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.

Cerebrospinal fluid dynamics and long-term survival of the Strata valve in idiopathic normal pressure hydrocephalus.

OBJECTIVE: Cerebrospinal fluid (CSF) dynamics and long-term shunt survival of the Strata CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). SUBJECTS AND METHODS: Seventy-two patients with INPH received a Strata valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long-term shunt survivals were obtained from patient records. RESULTS: The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty-nine patients (72%) had an improved gait. Two patients were improved despite non-functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6-month follow-up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. CONCLUSIONS: The long-term survival of the Strata valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti-siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.

Enabling nursing students to focus on the Ottawa Charter and the nurses role in tackling inequalities in health through international exchange.

Student nurses in a transatlantic exchange program explored the role of registered nurses in five countries' public health systems. The Ottawa Charter provided a framework for students to examine the nurse's responsibilities in public health. Students took practice placements in geographically rural a reason another continent and explored inequalities in health care. If nurses are to understand their role in the health care system then they must be taught the scope of their practice including their role in health promotion,public health practice and community development. For this project nursing instructors developed an assignment relevant to the aims and suitable for students in all five nursing programs. Only three of 48 students offered an assignment which focused on building healthy public policy. Nurse educators need to explore this further to ensure nurses of the future are aware of their role and responsibilities in this area and have skills to work effectively to influence and build healthy policy. The international student exchange supported the students' developing understanding of the breadth of initiatives around the globe where nurses are actively engaged in addressing inequalities of health. Findings from an analysis of their assignments are presented in this evaluative report.

Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations.

Celiac disease is a chronic inflammation of the small intestine, arising in genetically predisposed individuals as a result of ingestion of dietary gluten. The only confirmed and functionally characterised genetic risk factors for celiac disease are the DQ2 or DQ8 heterodimers at the major histocompatibility complex (MHC) class II locus (CELIAC1). These genes are necessary but alone not sufficient for disease onset. Genome-wide linkage scans have suggested chromosome 5q31-q33 (CELIAC2) as an important risk locus for celiac disease. This region has also been associated to other inflammatory disorders, although as yet, no clear gene associations have been found. In the current study, 11 celiac disease candidate loci were screened for genetic linkage in the Hungarian population. As the CELIAC2 locus showed the strongest evidence for linkage, this locus was selected for follow-up. Seventeen candidate genes were selected from the CELIAC2 locus, and genotyped using 48 haplotype tagging single nucleotide polymorphisms (SNPs) in large Finnish and Hungarian family materials. A subset of these, 40 tagging SNPs in 15 genes, were genotyped in an independent set of Finnish and Hungarian cases and controls. We confirmed linkage of this region with celiac disease and report strong linkage in both the Finnish and Hungarian populations. The association analysis showed modest associations throughout the whole region. These association findings were not replicated in the case-control datasets. Our study strongly supports the role of the CELIAC2 locus in celiac disease, but it also highlights the need for a more powerful study design in the region, to locate the true disease risk variants.

S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy.

OBJECTIVE: To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. METHODS: Subjects included in a prospective double blind randomised study for sTBI. INCLUSION CRITERIA: Glasgow Coma Score (GCS) 10 mm Hg and arrival <24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. RESULTS: 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) microg/l and for NSE 18.94 (2.32) microg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4-8 and GOS 2-5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1-3) and favourable (GOS 4-5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2-5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. CONCLUSION: At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.

Linkage and association study of FcgammaR polymorphisms in celiac disease.

The Fcgamma receptor cluster on chromosome 1q23 contains a number of genes that may affect susceptibility to celiac disease, but previous studies have yielded contradictory results. We studied the FcgammaRIIa*A519G (rs1801274) and FcgammaRIIIa*A559C (rs396991) single nucleotide polymorphisms in celiac disease families from Hungary and Finland and in celiac disease case-control materials from Hungary and Italy. Neither the Hungarian nor the Italian case-control material or a meta-analysis of the combined case-control material showed significant single-marker or haplotype association. In addition, neither linkage nor family-based association tests showed evidence for association in the Finnish or Hungarian family material. This study thus does not support a previous publication showing FcgammaR association with celiac disease.

The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency.

IgA deficiency (IgAD) and common variable immunodeficiency (CVID) often co-occur in families, associating with chronic inflammatory diseases such as celiac disease (CD). ICOS (inducible co-stimulator) and CTLA4 (cytotoxic T-lymphocyte-associated protein-4) may be important in both disorders, as ICOS is necessary for Ig class-switching and CTLA4 negatively regulates T-cell activation. Linkage and association of CD with CTLA4-ICOS is well documented, we thus aimed to further pinpoint CD susceptibility by haplotype-tagging analysis. We genotyped 663 CD families from Finland and Hungary, 575 additional CD patients from Finland, Hungary and Italy; 275 Swedish and Finnish IgAD individuals and 87 CVID individuals for 14-18 genetic markers in CTLA4-ICOS. Association was found between CTLA4-ICOS and both IgAD (P=0.0015) and CVID (P=0.0064). We confirmed linkage of CTLA4-ICOS with CD (LOD 2.38, P=0.0005) and found association of CTLA4-ICOS with CD (P=0.0009). Meta-analysis of the IgAD, CVID and CD materials revealed intergenic association (P=0.0005). Disease-associated markers were associated with lower ICOS and higher CTLA4 expression, indicating that the risk haplotypes contain functional variants. In summary, we identified a novel shared risk locus for IgAD, CVID and CD, the first report of association between CTLA4-ICOS and IgAD. Association between CD and CTLA4-ICOS was also confirmed in a large European data set.