Increased arterial stiffness and reduced left ventricular long-axis function in patients recovered from peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is idiopathic pregnancy-associated heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We aimed to assess arterial stiffness and left ventricular (LV) function in women recovered from PPCM compared with controls. METHODS: Twenty-two PPCM patients were compared with 15 age-matched controls with previous uncomplicated pregnancies. Eleven of the patients were at inclusion in the study recovered and off medication since at least 6 months and still free from cardiovascular symptoms with normal LVEF and normal NT-proBNP. All underwent echocardiography, including LV strain, left atrial (LA) reservoir strain and tissue Doppler early diastolic velocity (e´) and non-invasive assessment for arterial stiffness and central aortic systolic blood pressure (AoBP) at rest and immediately postexercise. RESULTS: The patients off medication showed alterations compared with controls. AoBP was higher (120 ± 9 mm Hg vs. 104 ± 13 mm Hg; p = .001), a difference which persisted postexercise. The arterial elastance was higher (1.9 ± 0.4 mm Hg/ml vs. 1.3 ± 0.2 mm Hg/ml; p < .001), while there were lower e´ septal (8.9 ± 1.7 cm/s vs. 11.0 ± 1.1 cm/s; p = 0. 002), LV global strain (18.7 ± 3.9% vs. 23.1 ± 1.6%; p = .004) and LA reservoir strain (24.8 ± 9.1% vs. 37.7 ± 6.3%; p = .002). CONCLUSIONS: Compared with healthy controls, PPCM patients considered recovered and off medication had increased arterial stiffness, decreased LV longitudinal function and reduced LA function.

Importance of software version for measurement of arterial stiffness: Arteriograph as an example.

BACKGROUND: Current guidelines recommend the measurement of arterial stiffness in terms of aortic pulse wave velocity (PWV) as an important cardio-vascular risk marker. Both aortic PWV and the aortic augmentation index (AIxao) can be measured using different techniques, e.g., the Arteriograph and SphygmoCor. A new version of the software for the Arteriograph (v. 3.0.0.1, TensioMed, Budapest, Hungary; Arteriograph II) is now available. We wanted to determine whether this improved software differs from the previous version (Arteriograph v. 1.9.9.12; Arteriograph I). We compared the estimated aortic PWV (ePWVao) and AIxao measured with both versions of Arteriograph software and analysed the agreement of these values with those measured by SphygmoCor (v. 7.01, AtCor Medical, Sydney, Australia). METHODS: Eighty-seven subjects without known cardio-vascular disease (23 men and 64 women) aged 54.2 ± 8.7 years (mean ± standard deviation; range 33-68 years) were included in the study. Estimated PWVao and AIxao were measured by both Arteriograph and SphygmoCor. We compared Arteriograph I and Arteriograph II with each other and with SphygmoCor. RESULTS: Estimated PWVao measured by Arteriograph II was lower than that measured by Arteriograph I, while the AIxao was higher. Divergence in ePWVao values was especially noted above 9 m/s. Estimated PWVao measured by Arteriograph II (7.2 m/s, 6.6-8.0 [median, 25th-75th percentile]) did not differ from that measured by SphygmoCor (7.1 m/s, 6.7-7.9 [median, 25th-75th percentile]). However, the AIao measured by Arteriograph II was significantly higher (P < 0.001). CONCLUSION: Regularly upgraded software versions resulting from continuous technical development are needed for quality improvement of methods. However, the changes in software, even if the basic patented operational algorithm has not changed, may influence the measured values as shown in the present study. Therefore, attention should be paid to the software version of the method used when comparing arterial stiffness results in clinical settings or when performing scientific studies.

Experiences from Auditory Brainstem Implantation (ABIs) in four paediatric patients.

INTRODUCTION: Indications for auditory brainstem implants (ABIs) have been widened from patients with neurofibromatosis type 2 (NF2) to paediatric patients with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, or cochlear ossification after meningitis. We present four ABI surgeries performed in children at Uppsala University Hospital in Sweden since 2009. METHODS: Three children were implanted with implants from Cochlear Ltd. (Lane Cove, Australia) and one child with an implant from MedEl GMBH (Innsbruck, Austria). A boy with Goldenhar syndrome was implanted with a Cochlear Nucleus ABI24M at age 2 years (patient 1). Another boy with CHARGE syndrome was implanted with a Cochlear Nucleus ABI541 at age 2.5 years (patient 2). Another boy with post-ossification meningitis was implanted with a Cochlear Nucleus ABI24M at age 4 years (patient 3). A girl with cochlear aplasia was implanted with a MedEl Synchrony ABI at age 3 years (patient 4). In patients 1, 2, and 3, the trans-labyrinthine approach was used, and in patient 4 the retro-sigmoid approach was used. RESULTS: Three of the four children benefited from their ABIs and use it full time. Two of the full time users had categories of auditory performance (CAP) score of 4 at their last follow up visit (6 and 2.5 years postoperative) which means they can discriminate consistently any combination of two of Ling's sounds. One child has not been fully evaluated yet, but is a full time user and had CAP 2 (responds to speech sounds) after 3 months of ABI use. No severe side or unpleasant stimulation effects have been observed so far. There was one case of immediate electrode migration and one case of implant device failure after 6.5 years. CONCLUSION: ABI should be considered as an option in the rehabilitation of children with similar diagnoses.

Self-reported benefit, sound perception, and quality-of-life in patients with auditory brainstem implants (ABIs).

CONCLUSION: The majority of the patients used their auditory brainstem implants (ABIs) all the time, reporting that he/she would make the decision to receive an implant again if the decision were reconsidered. The findings support that the ABI is a valuable treatment in patients with type 2 neurofibromatosis (NF2) and in children with congenital inner ear and nerve anomalies or cochlear ossification. OBJECTIVE: To evaluate the patients who underwent ABI implantation in Uppsala during 1993-2013. This study analyzed patients' implant use, perception of environmental sounds, perceived benefit from the implant, and quality-of-life (QoL). METHOD: The NF2-patients (n = 20) comprised the majority of the patients, and there were a few non-NF2 pediatric patients (n = 4). The exclusion criteria included deceased patients (n = 4) and patients with no hearing sensations from the implant, or those with an inactivated ABI (n = 2). The data were collected from a questionnaire survey. RESULTS: Eleven adult patients and two pediatric patients answered the questionnaires. Eight of the adult patients used their implants 'always'. The two children always used their implants. Hearing problems had the largest negative effect on the QoL. The non-users and the users scored equally on the NFTI-QoL.

Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance.

To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima-media thickness in the radial and carotid arteries, echogenicity of the carotid intima-media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training.

Auditory brainstem implants (ABIs)--20 years of clinical experience in Uppsala, Sweden.

CONCLUSIONS: Even though sound perception may be limited after treatment with an auditory brainstem implant (ABI), it provides benefits and should be selectively offered to patients. Importantly the patients must be motivated, given reasonable expectations of outcome and offered long-term rehabilitation with a considerable 'learn to listen' period with the implant device. OBJECTIVES: To describe the clinical experiences and results of 24 ABI surgeries performed in Uppsala University Hospital between 1993 and 2013. METHODS: Most patients (n = 20) suffered from neurofibromatosis type 2 (NF2); a few patients (n = 4) were paediatric non-NF2 patients. The files were searched for information on the presurgery size of the vestibular schwannoma, whether the patient had undergone gamma knife treatment, the surgical approach, the side effects of the surgery and of the use of the implant, the electrode activation pattern and implant use, and categories of auditory performance (CAP) score. RESULTS: Our results show that many patients greatly benefited from an ABI, and most of the patients used their implants even though the hearing improvements usually consisted of awareness of surrounding sounds and improved lip-reading. No severe side effects were observed from implant stimulation.

Loud noise exposure and acoustic neuroma.

The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.

Long-term mobile phone use and acoustic neuroma risk.

BACKGROUND: There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. METHODS: We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). RESULTS: Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. CONCLUSIONS: The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

Erratum: Music structure determines heart rate variability of singers.

[This corrects the article on p. 334 in vol. 4, PMID: 23847555.].

Music structure determines heart rate variability of singers.

Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Coupling of heart rate variability (HRV) to respiration is called Respiratory sinus arrhythmia (RSA). This coupling has a subjective as well as a biologically soothing effect, and it is beneficial for cardiovascular function. RSA is seen to be more marked during slow-paced breathing and at lower respiration rates (0.1 Hz and below). In this study, we investigate how singing, which is a form of guided breathing, affects HRV and RSA. The study comprises a group of healthy 18 year olds of mixed gender. The subjects are asked to; (1) hum a single tone and breathe whenever they need to; (2) sing a hymn with free, unguided breathing; and (3) sing a slow mantra and breathe solely between phrases. Heart rate (HR) is measured continuously during the study. The study design makes it possible to compare above three levels of song structure. In a separate case study, we examine five individuals performing singing tasks (1-3). We collect data with more advanced equipment, simultaneously recording HR, respiration, skin conductance and finger temperature. We show how song structure, respiration and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously. Implications concerning the effect on wellbeing and health are discussed as well as the question how this inner entrainment may affect perception and behavior.

Role of tobacco use in the etiology of acoustic neuroma.

Two previous studies suggest that cigarette smoking reduces acoustic neuroma risk; however, an association between use of snuff tobacco and acoustic neuroma has not been investigated previously. The authors conducted a case-control study in Sweden from 2002 to 2007, in which 451 cases and 710 population-based controls completed questionnaires. Cases and controls were matched on gender, region, and age within 5 years. The authors estimated odds ratios using conditional logistic regression analyses, adjusted for education and tobacco use (snuff use in the smoking analysis and smoking in the snuff analysis). The risk of acoustic neuroma was greatly reduced in male current smokers (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23, 0.74) and moderately reduced in female current smokers (OR = 0.70, 95% CI: 0.40, 1.23). In contrast, current snuff use among males was not associated with risk of acoustic neuroma (OR = 0.94, 95% CI: 0.57, 1.55). The authors' findings are consistent with previous reports of lower acoustic neuroma risk among current cigarette smokers than among never smokers. The absence of an association between snuff use and acoustic neuroma suggests that some constituent of tobacco smoke other than nicotine may confer protection against acoustic neuroma.

Surgical treatment of patients with facial neuromas--a report of 26 consecutive operations.

OBJECTIVE: To analyze surgical treatment and outcome in patients with facial neuromas at a tertiary referral hospital. STUDY DESIGN: A chart review of 26 patients treated between 1971 and 2006, with questionnaire follow-up ranging from 2 to 19 years. All patients except one were operated with radical tumor removal approaches. RESULTS: Approximately 54% of the patients presented with symptoms related to the VIIth cranial nerve (facial palsy and facial spasm), 58% with symptoms related to the VIIIth cranial nerve (hearing deficit, tinnitus, and vertigo), and 8% related to the Vth cranial nerve (facial pain and facial sensory deficit). Approximately 39% presented with no facial symptoms. Twenty-one patients received a facial nerve graft from the greater auricular nerve or the sural nerve; 1 patient had an accessory-facial anastomosis. One patient had a subtotal tumor removal preserving the facial nerve. Three patients were not grafted. Most tumors (88%) affect the geniculate ganglion. Approximately 82% of the grafted patients regained a House-Brackmann facial nerve function (HB) grade III; 14% regained HB grades IV to V. No serious morbidity or mortality was reported. No recurrences have been reported where a total tumor removal was performed. CONCLUSION: Surgical removal of facial neuroma is a safe procedure with a low complication rate and a low recurrence rate. First symptoms are diverse and are predominantly derived from the facial and vestibulocochlear nerve. Facial nerve grafting is reliable, giving the patient an acceptable facial nerve function (HB III).

High-resolution array-CGH profiling of germline and tumor-specific copy number alterations on chromosome 22 in patients affected with schwannomas.

Schwannomas may develop sporadically or in association with NF2 and schwannomatosis. The fundamental aberration in schwannomas is the bi-allelic inactivation of the NF2 gene. However, clinical and molecular data suggest that these tumors share a common pathogenetic mechanism related to as yet undefined 22q-loci. Linkage studies in schwannomatosis, a condition related to NF2, have defined a candidate 22q-locus and excluded the NF2 gene as the causative germline mutation. Thus, analysis of aberrations in schwannomas may lead to the identification of putative gene(s) involved in the development of schwannoma/schwannomatosis. We profiled a series of 88 schwannomas and constitutional DNA using a tiling path chromosome 22 array. Array-CGH is a suitable method for high-resolution discrimination between germline and tumor-specific aberrations. Previously reported frequencies of 22q-associated deletions in schwannomas display large discrepancies, ranging from 30% to 80%. We detected heterozygous deletions in 53% of schwannomas and the predominant pattern was monosomy 22. In addition, three tumors displayed terminal deletions and four harbored overlapping interstitial deletions of various sizes encompassing the NF2 gene. When profiling constitutional DNA, we identified eight loci that were affected by copy number variation (CNV). Some of the identified CNVs may not be phenotypically neutral and the possible role of these CNVs in the pathogenesis of schwannomas should be studied further. We observed a correlation between the breakpoint position, present in tumor and/or constitutional DNA and the location of segmental duplications. This association implicates these unstable regions in rearrangements occurring both in meiosis and mitosis.

Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males.

OBJECTIVE: Low adipocyte IRS-1 protein expression is a biomarker for insulin resistance and early atherosclerosis. However, whether IRS-1 protein expression is related to systemic arterial stiffness, is unknown. METHODS AND RESULTS: Ten non-diabetic male subjects with low adipocyte IRS-1 protein expression (LIRS) were matched with 10 non-diabetic males with normal IRS-1 protein expression (NIRS). Augmentation index (AIx) and time for reflection of pulse wave (Tr) were studied with pulse wave analysis, both in the fasting state and during a euglycemic hyperinsulinemic clamp. The LIRS-group showed an increased fasting insulin concentration (fP-insulin 71+/-4 pmol/L versus 58+/-5 pmol/L; p=0.02 (mean+/-S.E.)), whereas glucose disposal rate during the clamp (8.7+/-0.8 mg/kg LBM/min versus 10.3+/-1.3 mg/kg LBM/min; n.s.) did not differ significantly. Blood pressure, lipid parameters, adiponectin, endothelin-1 and CRP concentrations were similar. However, in the basal state, AIx was increased (129+/-4% versus 116+/-2%; p<0.02) and Tr was decreased (150+/-3 ms versus 171+/-5 ms; p<0.01), suggesting stiffer vessels in the LIRS-group. The LIRS-group exhibited an attenuated AIx response to hyperinsulinemia compared to the NIRS-group. CONCLUSIONS: The data suggest that non-obese non-diabetic men with a low adipocyte IRS-1 protein expression have an increased systemic arterial stiffness.

Regeneration of human auditory nerve. In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion.

Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage.