Pathological Enlargement Research Articles

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mm Hg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 to 100 mm Hg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (April 2016) and the Cochrane Register of Studies (CENTRAL (2016, Issue 3)). Clinical trials databases were searched (April 2016) for details of ongoing or unpublished studies. We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms. Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. We identified no RCTs that met the inclusion criteria. We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Impact of endoscopic ultrasound-guided fine needle aspiration of small lymph nodes

Abstract Background: There is very limited literature on results of fine needle aspiration (FNA) of small (defined as ≤1 cm at long and short axis) lymph nodes, particularly in the setting of pyrexia of unknown origin (PUO). Methods: The study was conducted from July 2014 to December 2015 at a tertiary care center. A total of 34 endoscopic ultrasound (EUS)-guided FNAs in 33 patients were done for lymph nodes ≤1 cm at long and short axis and these were included in the analysis. Results: The study cohort comprised 33 patients; 23 males and 10 females, mean age of 58 ± 12 years. Indication of FNA was to look for malignancy (n = 15), PUO (n = 16), unexplained weight loss (n = 1), and presence of lymphadenopathy in prospective liver donor (n = 1). The FNA was taken from mediastinal nodes (n = 20, 14 subcarinal) and abdominal (n = 14, 8 at porta). The mean size of lymph nodes was 87 ± 11 mm at large axis and 68 ± 17 mm at short axis. A total of 3 (8.8%) FNAs were nondiagnostic (inadequate material). The cytopathologic diagnosis was malignancy in 8 (23.5%), granulomatous change in 8 (23.5%), and reactive lymphadenopathy in 15 (44.1%). Thus, EUS-guided FNA of these small nodes changed the management decisions in 44% of cases (one patient had tubercular lymphadenopathy at two sites). The 22-gauge EUS FNA needle was used in majority of patients (n = 26). There was no significant difference between pathologic (malignant and granulomatous) and reactive lymph nodes regarding size at long or short axis, ratio of long and short axis, hypoechogenicity, and sharply defined borders. Conclusion: EUS-guided FNA of small lymph nodes showed pathological enlargement in 44% of cases.

Underlying Hashimoto's Thyroiditis Negatively Affects the Evolution of Subclinical Hypothyroidism in Children Irrespective of Other Concomitant Risk Factors

The pediatric literature does not contain any studies comparing the evolution of Hashimoto's thyroiditis (HT)-related subclinical hypothyroidism (SH) with idiopathic SH longitudinally. In the present study, the two-year evolution of HT-related SH in 32 children with no concomitant risk factors (group A) was compared to that observed in 90 age-matched children with idiopathic SH (group B). The aim was to ascertain whether the association with HT could, per se, affect the evolution of thyroid status over time in SH children irrespective of other coexisting factors, such as thyromegaly, association with other autoimmune diseases, and/or concomitant therapies. During the two-year follow-up, the percentage of children whose thyrotropin (TSH) values increased >10 mIU/L was significantly higher in group A (p<0.0005), whereas the percentages of those who either maintained a stable TSH (5-10 mIU/L) or normalized the TSH (<5 mIU/L) were significantly higher in group B (p<0.025). Moreover, the percentage of children who developed a pathological thyroid enlargement during follow-up was significantly higher in group A (p<0.0005). The association with HT exerts a negative influence on the evolution over time of mild SH, irrespective of other concomitant risk factors. In children with mild and HT-related SH, the risk of a deterioration in thyroid status over time is high (53.1%), while the probability of spontaneous TSH normalization is relatively low (21.9%). In contrast, in children with mild and idiopathic SH, the risk of a deterioration in thyroid status over time is very low (11.1%), whereas the probability of spontaneous TSH normalization is high (41.1%).

Endovascular treatment for ruptured abdominal aortic aneurysm.

An abdominal aortic aneurysm (AAA) (pathological enlargement of the aorta) can develop in both men and women as they grow older. It is most commonly seen in men over the age of 65 years. Progressive aneurysm enlargement can lead to rupture and massive internal bleeding, a fatal event unless timely repair can be achieved. Despite improvements in perioperative care, mortality remains high (approximately 50%) after conventional open surgical repair. A newer minimally invasive technique, endovascular aneurysm repair (EVAR), has been shown to reduce early morbidity and mortality as compared to conventional open surgery for planned AAA repair. Emergency endovascular aneurysm repair (eEVAR) has been used successfully to treat ruptured abdominal aortic aneurysm (RAAA), proving that it is feasible in selected patients. However, it is not yet known if eEVAR will lead to significant improvements in outcomes for these patients or indeed if it can replace conventional open repair as the preferred treatment for this lethal condition. To assess the advantages and disadvantages of emergency endovascular aneurysm repair (eEVAR) in comparison with conventional open surgical repair for the treatment of ruptured abdominal aortic aneurysm (RAAA). This will be determined by the effect on short-term mortality, major complication rates, aneurysm exclusion, and late complications when compared with the effects in patients who have had conventional open repair of RAAA. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and CENTRAL (2014, Issue 2). Reference lists of relevant publications were also checked. Randomised controlled trials in which patients with a clinically or radiologically diagnosed RAAA were randomly allocated to eEVAR or conventional open surgical repair. Studies identified for potential inclusion were independently assessed for eligibility by at least two review authors. Data extraction and quality assessment were also completed independently by two review authors. Disagreements were resolved through discussion. Meta-analysis was performed using fixed-effect models with odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous data and mean differences with 95% CIs for continuous data. Three randomised controlled trials were included in this review. A total of 761 patients with a clinical or radiological diagnosis of RAAA were randomised to receive either eEVAR or open surgical repair. Overall risk of bias was low but one study did not adequately report random sequence generation, putting it at risk of selection bias, two studies did not report on outcomes identified in their protocol, indicating reporting bias, and one study was underpowered. There was no clear evidence to support a difference between the two interventions on 30-day (or in-hospital) mortality, OR of 0.91 (95% CI 0.67 to 1.22; P = 0.52). The 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, re-operation, amputation, and respiratory failure. Individual complication outcomes were reported in only one or two studies and therefore no robust conclusion can currently be drawn. For complication outcomes that did include at least two studies in the meta-analysis there was no clear evidence to support a difference between eEVAR and open repair. Six-month outcomes were evaluated in only a single study, which included mortality and re-operation, with no clear evidence of a difference between the interventions and no overall association. Cost per patient was only evaluated in a single study and therefore no overall associations can currently be derived. The conclusions of this review are currently limited by the paucity of data. From the data available there is no difference in the outcomes evaluated in this review between eEVAR and open repair, specifically 30-day mortality. Not enough information was provided for complications in order to make a well informed conclusion at this time. Long-term data are lacking for both survival and late complications. More high quality, randomised controlled trials comparing eEVAR and open repair for the treatment of RAAA are needed in order to better understand if one method is superior to the other, or if there is no difference between the methods on relevant outcomes.

Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH.

Abnormal subcortical components of the corticostriatal system in young adults with DLI: A combined structural MRI and DTI study

Developmental Language Impairment (DLI) is a neurodevelopmental disorder affecting 12% to 14% of the school-age children in the United States. While substantial studies have shown a wide range of linguistic and non-linguistic difficulty in individuals with DLI, very little is known about the neuroanatomical mechanisms underlying this disorder. In the current study, we examined the subcortical components of the corticostriatal system in young adults with DLI, including the caudate nucleus, the putamen, the nucleus accumbens, the globus pallidus, and the thalamus. Additionally, the four cerebral lobes and the hippocampus were also comprised for an exploratory analysis. We used conventional magnetic resonance imaging (MRI) to measure regional brain volumes, as well as diffusion tensor imaging (DTI) to assess water diffusion anisotropy as quantified by fractional anisotropy (FA). Two groups of participants, one with DLI (n=12) and the other without (n=12), were recruited from a prior behavioral study, and all were matched on age, gender, and handedness. Volumetric analyses revealed region-specific abnormalities in individuals with DLI, showing pathological enlargement bilaterally in the putamen and the nucleus accumbens, and unilaterally in the right globus pallidus after the intracranial volumes were controlled. Regarding the DTI findings, the DLI group showed decreased FA values in the globus pallidus and the thalamus but these significant differences disappeared after controlling for the whole-brain FA value, indicating that microstructural abnormality is diffuse and affects other regions of the brain. Taken together, these results suggest region-specific corticostriatal abnormalities in DLI at the macrostructural level, but corticostriatal abnormalities at the microstructural level may be a part of a diffuse pattern of brain development. Future work is suggested to investigate the relationship between corticostriatal connectivity and individual differences in language development.

Enlargment of Virchow-Robin spaces in cranial trauma: literature review

In this review it is discussed the role of mild traumatic brain injury as a cause of Virchow-Robin spaces (VRS) pathological enlargement. Anatomy and physiology of normal VRS, and their immunological role are described. Special attention is given to magnetic resonance imaging findings of both normal and enlarged perivascular spaces.

Epicardial fat and vascular risk

We comment on the associations between epicardial adiposity and cardiovascular disease (CVD) and associated risk factors. The effects of lifestyle measures and CVD drugs on cardiac adipose tissue are also discussed. Epicardial adipose tissue exerts cardioprotective properties; however, in cases of pathological enlargement, epicardial fat can lead to myocardial inflammation and dysfunction as well as left ventricular hypertrophy and coronary artery disease (CAD) due to paracrine actions that include increased production of reactive oxygen species, atherogenic and inflammatory cytokines. Cardiac adiposity is associated with CAD, obesity, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease, and chronic kidney disease, as well as with CVD risk factors such as lipids, hypertension, obesity markers, and carotid atherosclerosis. Due to its anatomical and functional proximity to the coronary circulation, epicardial adipose tissue may represent an even more direct CVD risk marker than central adiposity. Lifestyle measures and certain drugs may affect its thickness, although there are limited data currently available. The clinical implications of epicardial fat in daily practice remain to be established in future studies.

Tissue plasminogen activator regulates Purkinje neuron development and survival.

The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse's 10-fold-increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability.

Role of 3-D Conventional Angiography In Evaluation of Intra Carnial Aneurysms

Introduction: intracranial aneurysms are pathological enlargement of the brain arteries that are most commonly located in the circle of Willis. Intracranial aneurysms are relatively common with a prevalence of approximately 4%. The real danger of aneurysms is subarachnoid hemorrhage. 3D digital subtraction angiography has become a critical imaging tool in neuroradiology allowing for the visualization of detailed cerebral vasculature prior to any intervention. Aim of the work: The aim of this work is to evaluate the diagnostic performance of 3D conventional angiography in the evaluation of intracranial aneurysms compared with the conventional cerebral angiography. Methods: The studied group included 20 patients (5 men and 15 women) with subarachnoid hemorrhage or known to have cerebral aneurysms. All patients were subjected to conventional cerebral angiography and 3D cerebral angiography, using C-arm (Toshiba) rotational technique. Results: 3D digital subtraction angiography is superior to conventional digital subtraction angiography in 100% of the cases 3D imaging revealed the proper aneurysmal shape, size, precise assessment of its neck and relation to the surrounding vessels. Conclusion: Three-dimensional DSA improves the detection and delineation of intracranial aneurysms

Role of 3-D Conventional Angiography in Evaluation of Intra Carnial Aneurysms

Introduction: intracranial aneurysms are pathological enlargement of the brain arteries that are most commonly located in the circle of Willis. Intracranial aneurysms are relatively common with a prevalence of approximately 4%. The real danger of aneurysms is subarachnoid hemorrhage. 3D digital subtraction angiography has become a critical imaging tool in neuroradiology allowing for the visualization of detailed cerebral vasculature prior to any intervention. Aim of the work: The aim of this work is to evaluate the diagnostic performance of 3D conventional angiography in the evaluation of intracranial aneurysms compared with the conventional cerebral angiography. Methods: The studied group included 20 patients (5 men and 15 women) with subarachnoid hemorrhage or known to have cerebral aneurysms. All patients were subjected to conventional cerebral angiography and 3D cerebral angiography, using C-arm (Toshiba) rotational technique. Results: 3D digital subtraction angiography is superior to conventional digital subtraction angiography in 100% of the cases 3D imaging revealed the proper aneurysmal shape, size, precise assessment of its neck and relation to the surrounding vessels. Conclusion: Three-dimensional DSA improves the detection and delineation of intracranial aneurysms

Management of the Hepatic Lymph Nodes During Resection of Liver Metastases from Colorectal Cancer: A Systematic Review

The aim of this review is to assess the role of hepatic lymphadenectomy in patients undergoing liver resection for colorectal metastases. Meta-analysis of trials identified by a systematic literature search of the Medline, Embase and Central databases was performed. There were no randomized controlled trials which assessed the survival benefit to patients undergoing liver resection for colorectal metastases of either a routine or a ‘selective’ lymphadenectomy. The prevalence of nodal metastases after lymphadenectomy was 8.4 %. The overall 3-year and 5-year survival rates in patients with hepatic lymph node metastases undergoing hepatectomy were 21.8 % (63 of 288 patients) and 8.5 % (27 of 315 patients), respectively, compared with 58.2 % (1,366 of 2,346 patients) and 47.5 % (1,717 of 3,609 patients) in patients undergoing hepatectomy who had no hepatic nodal metastases. The odds ratios for 3-year and 5-year mortality in node positive disease compared with node negative disease were 4.54 (95 % confidence interval 3.15–6.54) and 6.33 (95 % confidence interval 4.28–9.36), respectively. In conclusion, long-term survival rates are low in patients undergoing hepatectomy with hepatic lymph node metastases. The poor outcome is irrespective of whether the nodal metastases are discovered following routine lymphadenectomy or are detected because of pathological enlargement. Further trials in this patient group are required.

Reduction glossectomy for large tongues

Pathological enlargement of tongue is caused by several conditions and diseases. In several instances, surgery remains the only viable option for complete cure. Persistent bleeding, compromised neuro-motor-sensory functions during the postoperative period are the most common complaints encountered after macroglossia correction. The tongue is a muscular organ, whose complex neuroanatomy is being unraveled slowly. Various types of macroglossia resections in unique clinical situations have been proposed by several clinicians till date. There has never been unanimously accepted resection for the treatment of macroglossia. This review article attempts to preview the cosmetic and functional components for resection designs.

Correlation Between Preoperative Staging Computerized Tomography and Pathological Findings After Nodal Sampling in Children with Wilms Tumor

Guidelines for staging Wilms tumor mandate regional lymph node sampling at nephrectomy. However, the usefulness of preoperative computerized tomography in staging lymph nodes has not been rigorously investigated. Thus, we correlated preoperative computerized tomography and pathological lymph node findings to establish a radiological criterion for pathological lymph node enlargement. We reviewed the medical records of children with Wilms tumor at our institution who underwent pre-chemotherapy surgery with lymph node sampling and had preoperative computerized tomography with contrast medium available for interpretation. Computerized tomography was independently reviewed by 2 radiologists blinded to the pathological findings. We collected data on the diameter of the largest regional lymph node identified and this measurement was correlated with the pathological results. A total of 52 children (25 male, 27 female) with a median age of 3.1 years (range 0.4 to 9.6) were identified. The median largest regional lymph node diameter was 6 mm (range 2 to 15). Of the children 10 (19.2%) had metastatic involvement of sampled lymph nodes. A radiological cutoff of 7 mm for lymph node positivity corresponded to a negative predictive value of 89.0%, a sensitivity of 70.0% and a specificity of 57.1%. A ROC curve was constructed with these data describing the prognostic ability of the diameter of the largest regional lymph node on preoperative computerized tomography to determine lymph node positivity in Wilms tumor, which revealed an AUC of 0.67 (95% CI 0.48-0.87, p = 0.09). By defining a radiological size cutoff for suspicious lymph nodes, preoperative computerized tomography for staging lymph nodes in Wilms tumor demonstrates potential clinical usefulness through risk stratification for therapy and future study design.

Anxiety responses and neurochemical changes in a kaolin-induced rat model of hydrocephalus

Object Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus. Methods A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxlyase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining. Results The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y–immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxlyase–immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats. Conclusions These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the central dopamine system.

Interaction between alk1 and blood flow in the development of arteriovenous malformations

Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.

The behavioral change of locomotor activity in a kaolin-induced hydrocephalus rat model: Evaluation of the effect on the dopaminergic system with progressive ventricle dilatation

Hydrocephalus is a pathological enlargement of the cerebral ventricle that results from an obstruction of the space containing cerebrospinal fluid (CSF) in the brain. Motor abnormalities, such as abnormal gait and posture, are frequently seen in patients with hydrocephalus. The present study was designed to investigate locomotor activity in the elevated plus maze behaviorally. Hydrocephalus was induced in Sprague–Dawley rats by injection of 0.1ml of 20% kaolin solution into the cisterna magna (n=14). Control rats received the same volume of saline (n=12). The rats were sacrificed at 3 days and 4 weeks after the elevated plus maze test. Tyrosine hydroxlyase (TH) immunoreactivity in the substantia nigra was evaluated by immunohistological staining. Hydrocephalic rats showed decreased motor activity for entries of arms when compared to control rats (p<0.05). Compared to control rats, the number of TH immunoreactive neurons was significantly decreased in hydrocephalic rats. These results suggest that decreased motor responses due to ventricle enlargement in hydrocephalic rats are associated with the functional impairment of the central dopamine system.

O.037 On-line evaluation of the CSF compensatory parameters during constant rate infusion test

Assessment of ventricular enlargement is subjective and based on the radiologist’s experience. Linear indices, such as the Evans Index (EI), have been proposed as markers of ventricular volume with an EI ≥ 0.3 indicating pathologic ventricular enlargement in any subject. However, normal range for EI measured on magnetic resonance imaging (MRI) scans are lacking in healthy elderly according to age and sex. We propose new age and sex specific cut-off values for ventricular enlargement in the elderly population.534 participants (53% women) aged 65–84 years; 226 patients with Alzheimer’s disease (AD), and 308 healthy elderly controls (CTR) from the AddNeuroMed and ADNI studies were included. The cut-off for pathological ventricular enlargement was estimated from healthy elderly categorized into age groups of 5 years range and defined as EI 97,5 percentile (mean + 2SD). Cut-off values were tested on patients with Alzheimer’s disease and a small sample of patients with probable idiopathic normal pressure hydrocephalus (iNPH) to assess the sensitivity.The range of the EI in healthy elderly is wide and 29% of the CTR had an EI of 0.3 or greater. The EI increases with age in both CTR and AD, and the overall EI for women were lower than for men (p < 0.001). New EI cut off values for male/female: 65–69 years 0.34/0.32, 70–74 years 0.36/0.33, 75–79 years 0.37/0.34 and 80–84 years 0.37/0.36. When applying the proposed cut-offs for EI in men and women aged 65–84, they differentiated between iNPH and CTR with a sensitivity of 80% and for different age and sex categories of AD and CTR with a sensitivity and specificity of 0–27% and 91–98%, respectively.The range of the EI measurements in healthy elderly is wide, and a cut-off value of 0.3 cannot be used to differentiate between normal and enlarged ventricles in individual cases. The proposed EI thresholds from the present study show good sensitivity for the iNPH diagnosis.

Nasal Obstruction in Children with Sleep-disordered Breathing

Nasal obstruction secondary to pathological enlargement of inferior nasal turbinates contributes to sleep-disordered breathing (SBD) in prepubertal children, but treatments designed to address turbinate enlargement are often not performed. The aims of these studies are: (1) to appreciate the contribution to SDB of untreated enlarged nasal turbinates in prepubertal children; and (2) to report our experience with treatment of enlarged nasal turbinates in young children with SDB. Children with enlarged nasal turbinates who underwent adenotonsillectomy (T&A) had significantly less improvement in postoperative apnoea-hypopnoea index (AHI) compared to those treated with concomitant turbinate reduction. Children in the untreated turbinate hypertrophy group subsequently underwent radiofrequency ablation of the inferior nasal turbinates; following this procedure, AHI was no different than AHI of those without hypertrophy. In an analysis of safety and effectiveness of radiofrequency treatment of the nasal turbinates, we found the procedure to be a well-tolerated component of SDB treatment. We conclude that radiofrequency (RF) treatment of inferior nasal turbinates is a safe and effective treatment in young prepubertal children with SDB. When indicated, it should be included in the treatment plan for prepubertal children with SDB. However, the duration of effectiveness is variable and therapy may need to be repeated if turbinate hypertrophy recurs.

Abstract 1855: Transmural Myocardial Repair with Engineered Heart Tissue Grafts

Engineered Heart Tissue (EHT) can be utilized to partially repair infarcted myocardium in rats. Here, we investigated the feasibility of EHT-grafts as transmural wall replacement in a heterotopic transplantation model. Methods: EHTs (diameter: 15 mm, thickness: 1– 4 mm) were generated from 12.5 ×10 6 neonatal rat heart cells, collagen type I, and matrigel. Similarly, non-contractile constructs were generated from rat cardiac fibroblasts (FB) and mesenchymal stem cells (MSC). Grafts were surgically inserted into large transmural defects (diameter: 6 mm) in the left ventricle of explanted donor hearts. Subsequently, “treated” hearts were transplanted into weight-matched (308±12 g; n=14), immune suppressed (cyclosporine, azathioprine, prednisolone) Wistar rats in heterotopic position. All transmural defects were also covered with an aortic patch to prevent bleeding from the ventricles. Sham surgeries included aortic patch implantations only. Heterotopic hearts were harvested after 28 days and subjected to morphological analyses by confocal laser scanning microscopy (CLSM). Results: Heart transplant weight at the time of implantation was 1.1±0.02 g (n=14). Heterotopic heart weight increased substantially in Sham (2.4±0.3 g, n=3) and FB-graft (2.1±0.1 g, n=3) animals, whereas MSC- (1.7±0.2 g, n=4) and EHT-graft (1.3±0.1 g, n=4; p&lt;0.05 vs. Sham) animals showed a smaller or no increase in weight, respectively. EHT grafts remained contractile throughout the observation period. CLSM revealed that EHT-grafts established oriented muscle bundles (actin and actinin staining) inside the transmural defects and were strongly vascularized (CD31 and smooth muscle actin staining; lectin labeling) leading to partial reconstitution of the myocardial continuity. This was not observed in animals with FB- and MSC-grafts. However, MSC-grafts, but not FB-grafts, contained newly formed vessels with a markedly larger diameter than observed in EHT-grafts (21±6 vs. 5±0.7 μm; p&lt;0.05). Conclusion: EHTs can be utilized as myocardial tissue grafts to reconstruct and prevent pathological enlargement of the left ventricle. This study constitutes a first step to establish a novel transmural myocardial repair technology involving fully bioengineered heart muscle.