Comparison of Neurovascular Coupling between Normal Tension Glaucoma Patients and Healthy Individuals with Laser Speckle Flowgraphy.

Background: The purpose of this pilot study was to investigate the differences in neurovascular coupling between Caucasian patients with normal tension glaucoma (NTG) and healthy subjects (HS) with laser speckle flowgraphy (LSFG). Methods: Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate of the whole optic nerve head (MA), of the big retinal vessels (MV) and of the microvasculature (MT) was analysed during continuous flicker light stimulation for four minutes. Results: We included 12 eyes from 12 Caucasian patients with a diagnosis of normal tension glaucoma and 12 eyes from 12 age- and sex-matched healthy individuals. MA, MV and MT all increased significantly in both groups during the observation period with no difference between the groups. Conclusion: Neurovascular coupling is detectable in NTG patients. Flicker light stimulation leads to a comparable increase in ocular blood flow in glaucoma patients and healthy individuals.

[Morphological retinal characteristics of patients with low vision due to diabetic macular edema]. / Morphologische retinale Charakteristika von Patienten mit einer Sehbehinderung infolge eines diabetischen Makulaödems.

BACKGROUND: The World Health Organisation (WHO) defines low vision as a best corrected visual acuity (BCVA) in the better eye between ≥0.5 logMAR and ≤1.3 logMAR. In diabetic macular edema (DME) the correlation between retinal morphology and function is not completely understood in patients with advanced visual impairment. OBJECTIVE: The aim of the study was to describe the pathomorphological similarities of DME in patients with low vision and to correlate them with clinical parameters. MATERIAL AND METHODS: Optical coherence tomography (OCT) and fluorescence angiography (FA) images were graded according to the SAVE protocol and correlated with BCVA, cataract grade and clinical parameters in order to elucidate joint features. RESULTS: Out of a total collective of 65 patients 24 had low vision and 18 of these 24 patients (75%) showed typical signs of atrophic edema according to SAVE protocol criteria (SAVE group 4); however, 6 patients were afflicted with less progressive forms of DME but still suffered from low vision. Common pathomorphological findings were a discontinuity of the ellipsoid zone (EZ; n = 18), loss of pseudosepta (n = 7), layer-disrupting cysts (n = 7) and hard exudates (n = 10). CONCLUSION: It is suggested that a disruption of the EZ, loss of pseudosepta and layer-disrupting cysts are signs of an advanced chronic DME causing low vision. A definition of characteristic pathomorphological patterns of chronic damage in OCT is important for a possible treatment discontinuation in the clinical routine.

[Testing and approach when non-organic visual loss is suspected]. / Prüfung und Vorgehen bei Verdacht auf nichtorganische Sehstörung.

Approximately 5% of the patients in the ophthalmological practice suffer from non-organic vision loss. In children non-organic vision loss has been observed from the age of 6 years. In order to be able to make a rapid diagnosis knowledge of the relevant clinical tests is decisive. If a patient shows signs of non-organic visual loss, diagnostic externalization of the visual function is crucial. Depending on the symptoms there are various tests, which can be used to differentiate between organic and non-organic disorders. For therapeutic and economic reasons an early diagnosis of a non-organic visual loss is crucial. Ophthalmologists need to differentiate between malingering and augmentation, where the patient is aware of the fraud and tries to gain personal benefit from it, and somatoform disorders. In the latter, a more sensitive approach is recommended.

Neuronal desynchronization as marker of an impaired brain network.

Synchronization is a central key feature of neural information processing and communication between different brain areas. Disturbance of oscillatory brain rhythms and decreased synchronization have been associated with different disorders including schizophrenia. The aim of this study was to investigate whether synchronization (in relaxed conditions with no stimuli) between different brain areas within the delta, theta, alpha (alpha1, alpha2), beta (beta1, beta2), and gamma bands is altered in patients with a neurological disorder in order to generate significant cortical enhancements. To achieve this, we investigated schizophrenic patients (SZO; N=17, 37.5±10.4 years, 15 males) and compared them to healthy subjects (CON; N=21, 36.7±13.4 years, 15 males) applying the phase locking value (PLV). We found significant differences between SZO and CON in different brain areas of the theta, alpha1, beta2 and gamma bands. These areas are related to the central and parietal lobes for the theta band, the parietal lobe for the alpha1, the parietal and frontal for the beta2 and the frontal-central for the gamma band. The gamma band revealed the most significant differences between CON and SZO. PLV were 61.7% higher on average in SZO in most of the clusters when compared to CON. The related brain areas are directly related to cognition skills which are proved to be impaired in SZO. The results of this study suggest that synchronization in SZO is also altered when the patients were not asked to perform a task that requires their cognitive skills (i.e., no stimuli are applied - in contrast to other findings).

Analysis of Infants Based on Data from the German Perinatal Survey of the Years 1994-2011 in Mecklenburg-Pomerania, Germany. Classification of Infants with regard to their Gestation Duration and Birth Weight.

BACKGROUND: The demographic change in -Germany describes an ongoing process of population development of which the eastern German states tend to be more affected. These ongoing changes have an influence on the reproductive behavior of the population. After twenty-three years of German reunification, the present study has investigated the question to what extent the somatic classification of newborns in Mecklenburg-Pomerania (M-P), Germany, is affected. MATERIAL AND METHODS: Newborn singleton births (n=174,084) were classified from the existing data of the German Perinatal Survey between 1994 and 2011. The rate of premature birth, SGA, and LGA rate as well as the rate of low birth weight ≤2,499 g were determined both gender-dependently and independently. In addition, a combined analysis of the rates has been taken into account. The obtained data material from M-P made it possible for the first time to compare by values. National and international reference studies were considered in this comparison. RESULTS: In M-P, the premature birth rate is 5.2%; the rate of newborns with low birth weight ≤ 2,499 g is 4.4%. Among newborns of ≤2,499 g and SGA newborns, girls compose a higher percentage (4.7%, 12.5%) compared to boys (4.0%, 7.4%). The premature birth rate and LGA newborns appear conversely. For these, the percentage of boys (5.6%, 12.6%) is higher than that of girls (4.8%, 7.0%). 60.6% of the gender non-specific newborns ≤2,499 g are simultaneously premature newborn infants. Only a very small percentage of 0.5% of SGA newborns is at the same time premature infants and newborns with low birth weight. CONCLUSIONS: By getting nationwide country-specific figures, a detailed analysis of the newborns in M-P can be performed. The analysis supports the existing national values and is a helpful addition for practice-oriented advice.

Analysis of infants based on data from the German Perinatal Survey of the years 1994-2011 in Mecklenburg-Pomerania, Germany: new percentile values for anthropometric measures of infants.

BACKGROUND: This communication presents precise percentile values for birth weight, birth length and cranial circumference of infants in Mecklenburg-Pomerania, Germany. MATERIAL AND METHODS: Based on data from the German Perinatal Survey of the years 1994-2011 in Mecklenburg-Pomerania, the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for birth weight, birth length and head circumference are specified. The measurements of a total of 174,084 infants from non-multiple births are shown. RESULTS: The statistically calculated percentile values are presented in tabular and graph forms. The mean birth weight of the infants was 3,437.8 g. The average age of the mothers was 27.9 years. The average duration of pregnancy was 39.4 complete weeks. CONCLUSIONS: The insights gained from many years of data collection are presented as standardised, regional percentile values and curves for Mecklenburg-Pomerania for the first time. The differentiated presentation for the federal state opens the possibility for individually tailored consultations in clinical practice and may provide support for recognised national curves for these values.

[TSH secreting adenoma of pituitary gland (TSHom) - rare cause of hyperthyroidism in pregnancy]. / TSH-sezernierendes Hypophysenadenom (TSHom) - seltene Ursache einer Hyperthyreose in der Schwangerschaft.

HISTORY AND ADMISSION FINDINGS: A 28 year-old woman in her first pregnancy was referred to the department of obstetrics and gynecology at 24 weeks of gestation because of pregnancy-induced hypertension. INVESTIGATIONS: Thyroid stimulating hormone (TSH), free T3 and free T4 were elevated. Antibody screening did not show antithyroid peroxidase (anti-TPO) antibodies and TSH receptor antibodies. Clinical findings were suspicious of TSH secreting pituitary tumour (TSH-om) or thyroid hormone resistance (RTH). In absence of clinical sings of elevated intracranial pressure magnetic resonance imaging (MR) was discussed but not carried out and planned after delivery. A visual-field defect was ruled out by orbital field evaluation. TREATMENT AND COURSE: Treatment with 3 × 50 mg propylthiouracil daily was initiated. However, normal fT3/fT4 titers could not be achieved. Serum levels were in the high normal ranges and TSH remained increased. The clinical situation of the patient improved resulting in a normal delivery at term. The healthy newborn was breast feed and MR imaging of the mother revealed a 5×8 mm tumor of the pituitary gland. CONCLUSION: In pregnant women with pregnancy-induced hypertension thyroid diseases have to be ruled out. Rare causes of hyperthyreoidism are TSH secreting pituitary tumors or thyroid hormone resistance (RTH). Treatment of choice for hyperthyreoidism in pregnancy is propylthiouracil. Normal vaginal delivery and breast feeding are possible. Following delivery it is mandatory to determine an individual treatment strategy.

[Hantavirus infection due to Dobrava-Belgrade virus in a third trimester pregnant woman]. / Hantavirusinfektion durch Dobrava-Belgrad-Virus bei einer schwangeren Patientin im 3. Trimenon.

HISTORY AND ADMISSION FINDINGS: A 20-year-old woman was admitted to our hospital because of acute renal failure. She was pregnant in the third trimester. She reported on nausea, feeling of sickness, vomiting, abdominal pain and consecutively gross hematuria and sinustachycardia. Under suspicion of premature labour the patient was admitted to an external hospital. An antibiotic therapy with intravenous ampicillin/sulbactam was initiated. Because of acute kidney injury the patient was transferred firstly to the university women's hospital and finally to the department of nephrology. Obesity, the clinical signs of pregnancy, dehydration and small edema of the lower legs were the main medical findings on examination. INVESTIGATIONS: Laboratory tests revealed hyperuricemia, virological tests detected an acute infection with Dobrava-Belgrade virus. The ultrasonography demonstrated a pregnancy in good condition and a dilated (physiological) renal pelvis but otherwise normal renal morphology. DIAGNOSIS, TREATMENT AND COURSE: A Hantavirus associated acute kidney failure due to infection with the Dobrava-Belgrade virus was diagnosed. The course of the acute renal failure was characterised by remission of all symptoms. Intermittent evaluation by an obstetrician and a nephrologist were done to diagnose maternal and/or fetal complications. A renal replacement therapy was not necessary. At the 41st week of gestation a healthy male infant was born. The development of the newborn was age-appropriate. CONCLUSION: Hantavirus infections should be considered in cases of pregnancy-associated acute kidney injury.

[Premenstrual Dysphoric Disorder (PMDD) as an independent disease]. / Die prämenstruelle dysphorische Störung (PMDS) als eigenständiges Krankheitsbild.

This paper provides an overview of premenstrual dysphoric disorder (PMDD) and its clinical relevance in differentiation to premenstrual syndrome (PMS). Regarding recent research on epidemiology, aetiology, symptoms and therapy, PMDD is a discrete disorder and has a good prognosis in cases of appropriate diagnosis and therapy. The information provided in this review will help to better integrate PMDD into the psychiatric diagnostic process; options for diagnosis and treatment are also presented.

PP117. Measurement of sFlt-1 and PlGF for prediction of pregnancy associated diseases.

INTRODUCTION: Severe preeclampsia is associated with characteristic changes of sFlt-1 and PlGF levels in the maternal serum. OBJECTIVES: The aim of our study is the determination of the predictive value of sFlt-1 and PlGF for preeclampsia and other pregnancy associated diseases in women with a pathological uterine Doppler measurement during the second trimester of pregnancy. METHODS: An updated analysis of an ongoing prospective trial will be presented. Criterion of inclusion was a bilateral pathological uterine Doppler measurement with an increase of the resistance index (RI) >95th percentile and/or a bilateral postsystolic notch during 19 and 24 weeks. Ratio of sFlt-1 and PlGF was repeatedly measured during pregnancy using a full-automated system (Elecsys®, Roche). RESULTS: Presently, we recruited 36 patients. Full data are available from 17 patients. Out of these in 23.5% (n=4) a delivery before 37 weeks was indicated. 41% of all newborns (7/17) showed a birth weight <5th percentile. 23.5% of all patients developed a hypertensive pregnancy disorder but without fulfilling the criterions of preeclampsia. Only two patients had a sFlt-1/PlGF ratio >95th percentile. In both cases we found severe fetal growth retardation. One of them developed a pregnancy related hypertension based on an antiphospholipid syndrome. CONCLUSION: The additional measurement of the sFlt-1/PlGF ratio in a high risk group of pregnancies may improve the prediction of severe pregnancy related diseases during the second trimester. But keeping the low incidence of severe preeclampsia in mind, the measurements seem to be only usefulness in a high risk population. Although we reported presently only of a small part of our study population the sFlt-1/PlGF ratio did not revealed a good specificity for prediction of preeclampsia. Pathological values were also found in cases with fetal growth retardation without signs of preeclampsia.

Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice.

Peripheral neuropathy is a common and major complication of diabetes, the underlying mechanisms of which are not fully understood. Using a mouse model of type II diabetes, the present study investigated the role of phosphodiesterase-5 (PDE5) in peripheral neuropathy. BKS.Cg-m+/+Leprdb/J (db/db) mice were treated with sildenafil, a specific inhibitor of PDE5, at doses of 2 and 10 mg/kg or saline. Levels of PDE5 and morphometric parameters in sciatic nerve tissue as well as the motor and sensory function were measured in these mice. In diabetic mice, PDE5 expression in sciatic nerve tissue was significantly upregulated, whereas the myelin sheath thickness, myelin basic protein (MBP), and subcutaneous nerve fibers were significantly reduced. Treatment with sildenafil significantly improved neurological function, assayed by motor and sensory conducting velocities and thermal and mechanical noxious stimuli, concomitantly with increases in myelin sheath thickness, MBP levels, and subcutaneous nerve fibers. In vitro, hyperglycemia upregulated PDE5 in Schwann cells and reduced Schwann cell proliferation, migration, and expression of brain-derived neurotrophic factor (BDNF). Blockage of PDE5 with sildenafil increased cyclic guanosine monophosphate (cGMP) and completely abolished the effect of hyperglycemia on Schwann cells. Sildenafil upregulated cGMP-dependent protein kinase G I (PKGI), whereas inhibition of PKGI with a PKG inhibitor, KT5823, suppressed the inhibitory effect of sildenafil on Schwann cells. These data indicate that hyperglycemia substantially upregulates PDE5 expression and that the cGMP/PKG signaling pathway activated by sildenafil mediates the beneficial effects of sildenafil on diabetic peripheral neuropathy.

[The impact of a university ENT emergency centre for the ambulatory care of ENT emergency patients]. / Stellenwert der Notfallambulanz einer Universitäts-HNO-Klinik für die ambulante Patienten-Versorgung.

BACKGROUND: The impact of a German University ENT emergency unit has not been investigated yet. The present study had the aim to define the role of such an ENT emergency unit for the medical supply of ENT emergency cases. Patients' characteristics, diagnostics and therapeutical processes have been analysed. METHODS: In a retrospective study 3 695 emergency cases of the year 2004 have been characterized. RESULTS: Patients referring to the ENT emergency unit are relative young with an average age of 36 years. 72% are coming from the urban area. Two thirds referred themselves without seeing another physician before. The spectrum of diagnoses was broad, mainly similar to the normal spectrum of diseases seen in daily outpatient practice. 17% were emergency cases in narrower sense needing direct help because of real threat. 25% of the patients needed more than a clinical ENT examination. 9% of the cases were admitted to the hospital. DISCUSSION: In a major city without specialised outpatient ENT emergency system patient are attracted regularly to present at the University ENT emergency unit. This means a significant work load for the resident on duty. Most of the patients have ENT diseases treatable with this one and last patient contact. On the other hand, the hospital recruits an important amount of patients for inpatient treatment through the emergency unit.

Two different entities of spontaneous ovarian hyperstimulation in a woman with FSH receptor mutation.

Spontaneous ovarian hyperstimulation syndrome (OHSS) is an extremely rare event. Normally OHSS is seen in the context of IVF. In 2003 a mutation of the FSH receptor (FSHR D567N) was identified for the first time as a cause of spontaneous OHSS. In most FSHR mutations, a hypersensitivity to human chorionic gonadotrophin (HCG) or thyroid-stimulating hormone (TSH) is described. This clinical case presents for the first time two occurrences of spontaneous OHSS in a single woman with a FSHR mutation and two different entities. Pathophysiology of both pregnancies was completely different. During the first pregnancy, elevated HCG and androgen concentrations led to spontaneous OHSS and finally to miscarriage. The second pregnancy with spontaneous OHSS was dominated by a latent hypothyroidism and normal HCG concentrations and ended in a delivery of a healthy female newborn. Due to the unusual courses of the pregnancies, the study looked for a mutation in the FSHR and surprisingly identified the same mutation previously described. This report confirms for the first time the in-vitro findings in a single clinical case that TSH as well as HCG leads to spontaneous OHSS in patients with FSHR D567N mutation. Hypothyroidism has to be treated or ruled out.

Effect of intravitreal ranibizumab in avascular pigment epithelial detachment.

PURPOSE: To evaluate long-term morphologic and functional changes after intravitreal ranibizumab in avascular pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD). PATIENTS AND METHODS: Interventional, prospective case series; the first group of six patients received three and the second group of six patients received six intravitreal injections of ranibizumab (0.5 mg) at monthly intervals. Outcome measures included the change of PED and retinal volume as determined by spectral domain optical coherence tomography (Cirrus), best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), and macular sensitivity using microperimetry (MP-1; Nidek Co. Ltd). RESULTS: The mean baseline PED volume of 1.33 mm3 decreased significantly by 42% at month 6 (-0.55 mm3, P<0.05). Compared to baseline no significant change was observed at months 9 and 12. BCVA, retinal volume, and macular sensitivity remained stable during the entire follow-up. In one case a tear of the retinal pigment epithelium was observed after five injections with a consequent decrease of BCVA of four lines. CONCLUSION: Treatment with intravitreal injections of ranibizumab may temporarily decrease the volume of avascular PED secondary to AMD, however this effect was not maintained over the 1-year study period. The treatment was ineffective for improving retinal function as measured with BCVA and microperimetry.

Morphological and functional analysis of the loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration.

AIM: To quantify and correlate the morphological and functional effects of the recommended loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration (AMD). METHODS: In a prospective, interventional clinical trial, 29 consecutive patients (29 eyes) with choroidal neovascularisation secondary to AMD received three initial monthly intravitreal injections of ranibizumab. During this loading regimen, best corrected visual acuity (BCVA) and microperimetry (MP) testing, as well as optical coherence tomography and fluorescein angiography (FA), were performed using a standardised protocol and the results correlated. RESULTS: Significant morphological and functional therapeutic effects were observed as early as 1 week following the first treatment. Throughout the loading-dose period, central retinal thickness, including intraretinal cysts and subretinal fluid, decreased fast and significantly (p<0.01); pigment epithelial detachment resolved less rapidly. The mean leakage area by FA decreased (p<0.01) and retinal function (BCVA and MP) increased significantly (both p<0.01). However, the change in morphology and function was only significant between baseline and week 1. There was no significant additional morphological or functional benefit following the second and third injection. CONCLUSION: The initial administration of intravitreal ranibizumab in neovascular AMD induced a significant effect on intra- and subretinal fluid and visual function; subsequent injections had a less pronounced effect. It remains to be determined whether this loading regimen should be mandatory in all patients or if a single dose regimen would lead to a comparable functional and morphological retinal improvement.

[The role of Stratus OCT in anti-VEGF therapy. Qualitative and quantitative assessment of neovascular AMD]. / Die Rolle des Stratus-OCT bei der Anti-VEGF-Therapie : Qualitative und quantitative Beurteilung bei neovaskulärer AMD.

BACKGROUND: The evaluation of OCT3 during anti-VEGF therapy. METHODS: A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months. RESULTS: The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation. CONCLUSION: During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.

[Gynecological and obstetric aspects of general practice]. / Hausarzt und Gynäkologe müssen sich als Team verstehen. Erinnern Sie lhre Patientinnen an die Krebsvorsorge.

The general practitioner called upon to provide medical care to the older woman for diseases other than gynecological or obstetric illness, should not neglect to recommend gynecological cancer screening, which is of particular importance in this group. In many differential diagnoses, the general practitioner must also give consideration to gynecological-obstetric aspects. Thus, for example, when a patient presents with lower abdominal pain, gynecological pathology must always be taken into account. Numerous preparations with differing actions and applications used in contraception or hormone therapy in the post-menopausal woman, require individual counseling by the gynecologist.