Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence.

Major depressive disorder (MDD) is a complex illness caused by both genetic and environmental factors. Antidepressant resistance also has a genetic component. To date, however, very few genes have been identified for major depression or antidepressant resistance. In this study, we investigated whether outbred heterogeneous stock (HS) rats would be a suitable model to uncover the genetics of depression and its connection to antidepressant resistance. The Wistar Kyoto (WKY) rat, one of the eight founders of the HS, is a recognized animal model of juvenile depression and is resistant to fluoxetine antidepressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair-like behavior and response to fluoxetine treatment. We assessed heritability of despair-like behavior and response to sub-acute fluoxetine using a modified forced swim test (FST) in 4-week-old HS rats. We also tested whether blood transcript levels previously identified as depression biomarkers in adolescent human subjects are differentially expressed in HS rats with high vs. low FST immobility. We demonstrate heritability of despair-like behavior in 4-week-old HS rats and show that many HS rats are resistant to fluoxetine treatment. In addition, blood transcript levels of Amfr, Cdr2 and Kiaa1539, genes previously identified in human adolescents with MDD, are differentially expressed between HS rats with high vs. low immobility. These data demonstrate that FST despair-like behavior will be amenable to genetic fine-mapping in adolescent HS rats. The overlap between human and HS blood biomarkers suggest that these studies may translate to depression in humans.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.

Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway.

OBJECTIVE: This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2+), and to discriminate pre-existing from newly-acquired infections. METHODS: Cervical specimens from 58 women (median age (Q1-Q3): 37.6 (31.7-44.9)) who underwent primary (1998-2003) and repeat conizations were confirmed as CIN2+ during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18. RESULTS: All 58 paired cones were HPV positive; 49 had CIN3+ in the primary cone. Forty-seven (95.9%) women with primary CIN3+ and recurrent CIN2+ had persistent high-risk (hr) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2+. Median time delay (Q1-Q3) between conizations was 2.0 years (1.1-4.0), being shorter for women older than 40 years: 2.6 years (1.1-3.7) than for women younger than 40 years: 6.0 years (2.0-8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3+ had a shorter delay between conizations: 1.8years (1.2-4.4) and 2.2 years (0.4-NE), respectively, compared to HPV33-: 3.8 years (3.3-7.8) or other HPV type-infected: 8.2 years (6.0-NE) CIN3+. CONCLUSIONS: Routine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2+ and its recurrence.

Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures.

Seed rain under tree islands planted to restore degraded lands in a tropical agricultural landscape.

Planting native tree seedlings is the predominant restoration strategy for accelerating forest succession on degraded lands. Planting tree "islands" is less costly and labor intensive than establishing larger plantations and simulates the nucleation process of succession. Assessing the role of island size in attracting seed dispersers, the potential of islands to expand through enhanced seed deposition, and the effect of planting arrangements on seed dispersal by birds and bats informs restoration design. Determining the relative importance of local restoration approach vs. landscape-level factors (amount of surrounding forest cover) helps prioritize methods and locations for restoration. We tested how three restoration approaches affect the arrival of forest seeds at 11 experimental sites spread across a gradient of surrounding forest cover in a 100-km2 area of southern Costa Rica. Each site had three 50 x 50 m treatments: (1) control (natural regeneration), (2) island (planting tree seedlings in patches of three sizes: 16 m2, 64 m2, and 144 m2), and (3) plantation (planting entire area). Four tree species were used in planting (Terminalia amazonia, Vochysia guatemalensis, Erythrina poeppigiana, and Inga edulis). Seed rain was measured for 18 months beginning approximately 2 years after planting. Plantations received the most zoochorous tree seeds (266.1 +/- 64.5 seeds x m(-2) x yr(-1) [mean +/- SE]), islands were intermediate (210.4 +/- 52.7 seeds x m(-2) x yr(-1)), and controls were lowest (87.1 +/- 13.9 seeds x m(-2) x yr(-1)). Greater tree seed deposition in the plantations was due to birds (0.51 +/- 0.18 seeds x m(-2) x d(-1)), not bats (0.07 +/- 0.03 seeds x m(-2) x d(-1)). Seed rain was primarily small-seeded, early-successional species. Large and medium islands received twice as many zoochorous tree seeds as small islands and areas away from island edges, suggesting there is a minimum island size necessary to increase seed deposition and that seed rain outside of planted areas is strongly reduced. Planting design was more important for seed deposition than amount of forest cover within the surrounding 100- and 500-m radius areas. Establishing plantations and large islands facilitates the arrival of early-successional tree seeds and represents a broadly applicable strategy for increasing seed rain on abandoned agricultural lands. However, more intensive restoration approaches may be necessary for establishment of dispersal-limited species.

Recurrent cryptic vascular malformation associated with a developmental venous anomaly.

Abnormal venous drainage patterns, such as developmental venous anomalies (DVAs), are frequent findings neighbouring cryptic vascular malformations (CVMs). Although the clinical relevance of DVAs remains controversial, increasing attention has been focused on the possible importance of venous outflow disturbance and venous hypertension in DVAs for the development of CVMs. We present the case of a 32-year-old man with dysphasic seizures symptomatic for recurrence and rebleeding of a CVM of the left angulare gyrus, which drained entirely into a large DVA. A cavernoma had been surgically removed 1 year before, while the associated DVA had been left in place. In the following second surgical procedure, the new malformation, which was histologically verified as arteriovenous angioma (AVM), was removed and the DVA was occluded for the length of the angioma. Postoperative course of the patient was unremarkable, the patient is seizure free and neurologically intact. This first report of such a sequence of events raises important questions regarding the association of various vascular malformations, regarding transitional and hybrid forms, as well as the role of anomalous venous drainage in their pathophysiology and probably in their development. Our case and selected cases in literature suggest that venous hypertension in a DVA might not be just a coincidential finding, but sometimes can induce or influence the development and recurrence of associated vascular lesions. The developmental interrelationship, the potential mechanisms for this association and the implications of similar cases reported in pertinent literature are discussed.

Distributed nuclear medicine applications using World Wide Web and Java technology.

At present, medical applications applying World Wide Web (WWW) technology are mainly used to view static images and to retrieve some information. The Java platform is a relative new way of computing, especially designed for network computing and distributed applications which enables interactive connection between user and information via the WWW. The Java 2 Software Development Kit (SDK) including Java2D API, Java Remote Method Invocation (RMI) technology, Object Serialization and the Java Advanced Imaging (JAI) extension was used to achieve a robust, platform independent and network centric solution. Medical image processing software based on this technology is presented and adequate performance capability of Java is demonstrated by an iterative reconstruction algorithm for single photon emission computerized tomography (SPECT).

Advanced surgical approach for selective amygdalohippocampectomy through neuronavigation.

OBJECTIVE: Selective removal of the mesiobasal temporal structures through the transsylvian approach was introduced by Yasargil and Wieser in 1982. This alternative to standard temporal lobectomy provides excellent outcomes for seizure control. Basic actions in the transsylvian fissure exposure mainly serve to orient the surgeon, and they carry the risk of vasospasm and vessel damage. The aim of our study was to reduce landmark-guided surgery steps through neuronavigation. METHODS: During a 14-month period, 16 selective amygdalohippocampectomies were performed with the aid of the SMN (Carl Zeiss, Inc., Thornwood, NY) or StealthStation (Sofamor Danek, Memphis, TN) optically guided systems. We added safety procedures to the operation (including intraoperative rereferencing, obtaining additional bony reference points before craniotomy, performing a small craniotomy and making an accurate dural incision, and using contrast medium for vessel visualization) to develop a method that relies on navigational systems without further orientation by anatomic landmarks. RESULTS: Originally, performing an amygdalohippocampectomy required exposing the sylvian fissure from the carotid bifurcation to 2 cm beyond the middle cerebral artery bifurcation, which exposed one-third of the insula. By determining the entry point at the limen insulae and the target at the tip of the temporal horn, the mandatory extent of the opening to the sylvian fissure can be projected. Therefore, the exposure of the fissure can be limited to exactly the extent required for the transventricular approach through the uncinate fasciculus. CONCLUSION: Computer-assisted surgery is an effective tool in eliminating the exposure of anatomic landmarks in selective amygdalohippocampectomy. This modification combines the precision of targeting with minimal cortical and vessel traumatization.

A Jini service to reconstruct tomographic data.

Distributed computing that uses dynamic networks will change the way we work and communicate thanks to the interaction of devices and services, that are automatically added and removed from the network as needed. The Jini technology, which is built atop the Java programming language, provides a homogenous view of the network and extends the ability of code to migrate in Java. This software design model simplifies the configuration and access to hardware devices and software services in a network. Thus, it becomes possible to execute new services without pre-installing software on client machines. This new programming paradigm is especially important in medical applications, where the reliable transmission of information is essential. This paper demonstrates how single photon emission computerized tomography data can be iteratively reconstructed using a Jini service.

Microsurgical management of a complicated aneurysmal endovascular embolisation with GDC coil: a case report.

We present a case involving a microsurgical approach to solving the problem of a medial cerebral artery (MCA) occlusion occurring after GDC coiling of an internal cerebral artery (ICA) bifurcation aneurysm in a 40 year old woman. We describe the clinical course of the case and discuss technical possibilities and risks of clipping a coiled aneurysm. One key to success is awareness of changes in the aneurysm's properties after coiling. With loss of elasticity the aneurysm had the effect of a tumor fixed on the vessel. The apposition of the aneurysm to the wall of the vessel, as well as the aneurysm's rigidity and increase of intracranial pressure after subarachnoideal hemorrhage (SAH), may lead to occlusion of the vessel. In cases of an mandatory operation due to the occlusion of a main arterial stem after coiling, it is primarily crucial to perforate the aneurysm's fundus, remove the coils, and, finally, to clip the slack neck of the aneurysm. An attempt to precisely prepare and clip the aneurysmal neck without removing the coils could result in the rupture of the aneurysm's neck.

A T1-weighted rapid three-dimensional gradient-echo technique (MP-RAGE) in preoperative MRI of intracranial tumours.

Our purpose was to determine the value of a T1-weighted rapid three-dimensional gradient-echo technique in preoperative MRI of brain tumours. We examined 30 patients with intracranial tumours who underwent neurosurgery, using T1-weighted magnetisation-prepared rapid gradient-echo (MP-RAGE) and axial T1-weighted spin-echo (SE) sequences, both before and after contrast medium (Gd-DTPA). Signal and contrast behaviour of anatomical and pathological structures were assessed with regions-of-interest (ROI) and visual inspection. Imaging results were compared with operative results. In 5 cases tumours and anatomical structures were segmented in MP-RAGE data sets. The MP-RAGE sequence considerably improved delineation of grey and white matter and small anatomical structures (vessels, cranial nerves), and significantly reduced flow artefacts. Contrast behaviour of tumours was similar with both techniques. Correlation of imaging with the operative results confirmed the reliability of the MP-RAGE sequence. Segmentation of MP-RAGE data sets allows three-dimensional display, which enables one to document the relevant information on a few images in selected cases.

[Stereotaxically guided versus ultrasound guided surgery--a comparative report of experiences]. / Stereotaxiegeführtes versus ultraschallgeführtes Operieren--Ein vergleichender Erfahrungsbericht.

Localisation and approach are the keys of surgery on brain tumours. Apart from the up and coming neuronavigational devices, stereotactical and ultrasound guidance are well established methods in locating intracranial tumours and in selecting the optimal approach for resection. Nevertheless it is not clear, which guidance tool is more practicable in the daily routine. Both methods have been used in our department since 1989. During the last six and half years we have operated on 1314 patients suffering from intracranial tumours. In 148 cases we have used either stereotactical (n = 37) or ultrasonic (n = 111) intraoperative guidance. The performing surgeon had documented ease of use, accuracy and users acceptance of the chosen guidance tool. The data were summarised together with the patients history and images in to a descriptive report. Since 1992 we noted a steady increase in guiding operations from 4% to 24%, mainly due to the more frequent use of ultrasound guidance. Saving time, easy handling, accuracy and plausible guidance with real time pictures have been the major advantages in favouring ultrasound guidance. Additionally, the freedom in choosing the appropriate approach seems to be essential. To achieve full advantage of all these benefits, experience and individual expertise are necessary. Conversely, the high accuracy of stereotactic guidance is not within the reach of the ultrasound, which is sufficient to guide the operation. According to our experiences, we recommend intraoperative ultrasound as an easy guiding tool. Except a few cases, this guiding tool seems to be superior to the stereotactic localisation of intracranial lesions.

[Stable xenon computed tomography. Methodology and clinical application]. / Die Stable-Xenon-Computertomographie. Methodik und klinische Anwendung.

According to the principle of the dynamic computed tomography, stable xenon computed tomography allows measurement of the increase in density caused by xenon in the brain tissue. During a period of about 4 min a patient inhales a mixture of xenon (33%) and oxygen. By means of a special software, this method can be used to calculate flowmaps and to determine the local cerebral blood flow in a 1 cm x 1 cm areal. Stable xenon computed tomography is used mainly for cerebral blood flow measurements in patients with cerebrovascular diseases and also allows calculation of cerebral reserve capacity following stimulation of blood flow by the carboanhydrase inhibitor acetazolamide (Diamox).

[Pneumatosis intestinalis--histology, immunocytochemistry and new theory of morphogenesis]. / Pneumatosis intestinalis--Histologie, Immunzytochemie und neue Theorie zur Morphogenese.

Based on the light microscopical and immunocytochemical findings in two cases of pneumatosis intestinalis, a new theory is advanced on the morphogenesis of the cysts that can be observed in this disease. The cavities identifiable in both cases in the submucosa of the small intestine and of the colon, respectively, were partially lined by histiocytes and foreign-body giant cells. Most of the lumina found in the subserosa of the stomach, small intestine and colon had an identical aspect. In addition, there were numerous true cysts here with a narrow, single-layered cells seam, showing the immunocytochemical characteristics of the mesothelium, but not the capillary endothelia. Thus, contrary to previous assumptions, pneumatosis interstinalis apparently does not develop from cystic dilatation of gas-filled lymph vessels that shrink and disappear in the process of an inflammatory foreign body reaction. Rather, the disease initially seems to manifest itself through gas-filled pseudocysts partially bordered by histiocytes and foreign-body giant cells, which become secondarily mesothelialized in the subserosa. Lymph vessels would thus not have significance for the morphogenesis of this disease.