Three-dimensional reconstruction of defects in congenital diaphragmatic hernia: a fetal MRI study.

OBJECTIVE: To assess the clinical feasibility and validity of fetal magnetic resonance imaging (MRI)-based three-dimensional (3D) reconstruction to locate, classify and quantify diaphragmatic defects in congenital diaphragmatic hernia (CDH). METHODS: This retrospective study included 46 cases of CDH which underwent a total of 69 fetal MRI scans (65 in-vivo and four postmortem) at the Medical University of Vienna during the period 1 January 2002 to 1 January 2017. Scans were performed between 16 and 38 gestational weeks using steady-state free precession, T2-weighted and T1-weighted sequences. MRI data were retrieved from the hospital database and manual segmentation of the diaphragm was performed with the open-source software, ITK-SNAP. The resulting 3D models of the fetal diaphragm and its defect(s) were validated by postmortem MRI segmentation and/or comparison of 3D model-based classification of the defect with a reference classification based on autopsy and/or surgery reports. Surface areas of the intact diaphragm and of the defect were measured and used to calculate defect-diaphragmatic ratios (DDR). The need for prosthetic patch repair and, in cases with repeated in-vivo fetal MRI scans, diaphragm growth dynamics, were analyzed based on DDR. RESULTS: Fetal MRI-based manual segmentation of the diaphragm in CDH was feasible for all 65 (100%) of the in-vivo fetal MRI scans. Based on the 3D diaphragmatic models, one bilateral and 45 unilateral defects (n = 47) were further classified as posterolateral (23/47, 48.9%), lateral (7/47, 14.9%) or hemidiaphragmatic (17/47, 36.2%) defects, and none (0%) was classified as anterolateral. This classification of defect location was correct in all 37 (100%) of the cases in which this information could be verified. Nineteen cases had a follow-up fetal MRI scan; in five (26.3%) of these, the initial CDH classification was altered by the results of the second scan. Thirty-three fetuses underwent postnatal diaphragmatic surgical repair; 20 fetuses (all of those with DDR ≥ 54 and 88% of those with DDR > 30) received a diaphragmatic patch, while the other 13 underwent primary surgical repair. Individual DDRs at initial and at follow-up in-vivo fetal MRI correlated significantly (P < 0.001). CONCLUSIONS: MRI-based 3D reconstruction of the fetal diaphragm in CDH has been validated to visualize, locate, classify and quantify the defect. Planning of postnatal surgery may be optimized by MRI-based prediction of the necessity for patch placement and the ability to personalize patch design based on 3D-printable templates. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.

AIMS: Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. METHODS: Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life. RESULTS: We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well. DISCUSSION: Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.

[The Influence of Intravitreal Injections on Outpatient Cataract Operations in Germany]. / Der Einfluss der intravitrealen Injektionen auf die ambulante Intraokularchirurgie in Deutschland.

PURPOSE: The number of outpatient operations in Germany is not registered in a centralised manner. To estimate the development of the outpatient intraocular surgery especially since the implementation of the intravitreal injections, surveys among ophthalmic surgeons were analysed. METHODS: Between 2006 and 2013 surveys were done among ophthalmic surgeons in Germany using questionnaires. An average of 318 completed questionnaires were sent back. The mean participation ratio was 37 %. RESULTS: Between 2006 and 2013 an extrapolated mean of 347 564 cataract operations and 139 946 intravitreal injections were reported. Whereas the number of cataract operations was constant in the observation period, the number of injections increased considerably from 35 135 in 2006 to 274 714 in 2013. CONCLUSION: A saturation in the development of the numbers of the intravitreal injections could not yet be observed. Other outpatient operations, especially cataract procedures were not replaced by the increase of the injections in the recent years.

Localised Synovial Sarcoma in Adolescents and Young Adults Versus Adults - Is There a Difference in Outcome?

AIMS: Synovial sarcomas are a rare subgroup of soft-tissue sarcoma arising in adolescents and young adults (AYA) and in adult patients. The objective of our analysis was to investigate the outcomes and potential differences of AYA versus adult patients with initially localised disease. MATERIALS AND METHODS: In total, 51 patients (25 AYA and 26 adult) were identified and evaluated in this retrospective single centre analysis. Baseline characteristics, treatment and outcome were assessed. RESULTS: The predominant subtype in both groups was monophasic synovial sarcoma (17 AYA and 21 adult) and the most common site was the extremities (14 and 19 patients) with deep tumour location in both groups (33 and 24 patients). More AYA patients had tumours >5 cm (13/25 patients) when compared with adults (10/26 patients, P = n.s.). Primary wide resection was carried out in 15 AYAs and in 18 adults. Postoperative radiation therapy was the only statistical difference between AYA (n = 19) and adult patients (n = 12; P = 0.029). Nineteen and 17 patients, respectively, received adjuvant chemotherapy with no evidence of disease after six cycles. Nine and 11 patients relapsed after initial therapy and the most common metastatic site was the lung (eight versus nine patients). Five-year overall survival rates were 85% and 75%. Female gender, tumour size ≤5 cm and absence of progressive disease showed a significant association with overall survival in AYA patients (P = 0.013, P = 0.04 and P < 0.001), whereas non-extremity tumours and progression after initial therapy were significant for worse overall survival in adult patients (P = 0.012 and P < 0.001). No difference in overall survival between AYA and adult patients was observed (P = 0.899). CONCLUSIONS: AYA and adult patients showed no significant difference in terms of overall survival. Male gender, tumour size >5 cm and progressive disease were prognostic markers for worse outcome, whereas tumour location (non-extremity) and progression after initial therapy were markers for worse outcome in adult patients.

A clinical evaluation of the effects of topically applied levobunolol and timolol on increased intraocular pressure.

Data from two short-term double-masked studies using 24 and 16 subjects suggest that topically applied levobunolol safely and effectively treats open-angle glaucoma and ocular hypertension. The onset of effect of a single drop of 0.5% levobunolol occurred within the first hour, producing a maximal hypotensive effect of more than 8 mm Hg after two hours. An intraocular pressure deceased of greater than or equal to 2 mm Hg was still observed after 24 hours for both concentrations of levobunolol tested (0.5% and 1%). Intraocular pressure decreases of more than 9 mm Hg persisted during a one-month trial in which patients were treated twice daily, confirming the results obtained in the 24-hour study. Systemic effects of both timolol (0.5%) and levobunolol (0.5% and 1%) included a consensual intraocular pressure-decreasing effect in the untreated eye and clinically significant reductions in heart rate. Diastolic blood pressure was decreased at two and four hours after administration of 0.5% levobunolol.

Long-term ocular hypotensive effect of levobunolol: results of a one-year study.

Data for the first 12 months are reported for an ongoing, multicentre, clinical study comparing the long-term, ocular hypotensive efficacy and safety of topical levobunolol (0.5% and 1%) and timolol (0.5%). This study was a double-masked trial testing 88 patients with chronic open angle glaucoma or ocular hypertension. During the 12-month period drops were instilled twice daily into both eyes after a washout of prestudy ocular hypotensive medication. The effect of the three treatments in reducing intraocular pressure (IOP) was similar. Mean IOP reductions over the 12 months averaged 7.2 mmHg for the 0.5% levobunolol group, 6.2 mmHg for the 1% levobunolol group, and 6.0 mmHg for the timolol group. Decreases in mean heart rate of up to 5 beats per minute were observed in the 0.5% levobunolol group, up to 8 beats per minute in the 1% levobunolol group, and up to 4 beats per minute in the timolol group. Several patients were removed from the study owing to side effects possibly related to levobunolol treatment.

[Complications of foldable intraocular lenses requiring explantation. Results of the 2000 and 2001 survey in Germany]. / Komplikationen faltbarer Intraokularlinsen mit der Folge der Explantation. Untersuchungsergebnisse der Jahre 2000 und 2001.

PURPOSE: A survey was sent to all members of the German Society of Ophthalmic Surgeons to evaluate complications that required explantation of foldable intraocular lenses (IOLs). METHODS: Data on preoperative visual acuity, foldable IOL design and material, and the reason for explantation were obtained and analysed. We received 185 surveys for 2000 and 2001. RESULTS: In 2000 and 2001, the most common reasons for IOL explantation were: incorrect lens power (31%) and dislocation (19%) in three-piece acrylic IOLs, incorrect power (31%) and decentration (17%) in monofocal silicone IOLs, and opacification (46%) in hydrophilic IOLs. The most common reasons for the exchange of monofocal IOLs were lens opacification in 2000 and incorrect IOL power in 2001. CONCLUSION: Besides the most frequent complications of decentration and incorrect power observed in rigid IOLs,new complications associated with foldable IOLs occurred (e.g., optic opacification and calcification). Accurate calculation of IOL power and further improvements in material and design are still necessary to minimize the rate of explantations.

[Complications with foldable intraocular lenses with subsequent explantation in 1998 and 1999. Results of a questionnaire evaluation]. / Komplikationen faltbarer Intraokularlinsen mit der Folge der Explantation von 1998 und 1999. Ergebnisse einer Fragebogenauswertung.

PURPOSE: A questionnaire was sent to all members of the German Society of Ophthalmic Surgeons to evaluate complications of foldable intraocular lenses (IOLs) that required explanation. METHODS: Information on preoperative visual acuity, foldable IOL design and material as well as the reason for IOL explantation was obtained and analysed. We received 167 completed questionnaires for 1998 and 1999. RESULTS: In 1998 and 1999 the most common reasons for IOL explantation were as follows: incorrect lens power for 56% of the 3-piece hydrophobic acrylic IOLs, 16% because of glare or other photic phenomena, 40% of the 1-piece hydrophilic acrylic IOLs were explanted because of incorrect lens power and 30% for IOL damage. For the 3-piece monofocal silicone IOLs, 41% were explanted because of incorrect IOL power and 32% because of IOL decentration. For the 1-piece Hydrogel IOL, 76% were explanted because of opacification of the optic and 14% because of incorrect lens power. Most multifocal IOLs were explanted because of photic phenomena. CONCLUSION: In addition to the most common complications such as decentration and incorrect IOL power observed in rigid IOLs, new complications associated with foldable IOLs occurred such as optic opacification, glare and photic phenomena. Some complications seemed to appear in particular IOL types (opacification: SC-60BOUV, MDR), while others were observed in all types of foldable lenses. Accurate calculation of the IOL power and further improvement of the IOL material and design seem to be necessary to minimise the rate of explantations.

Influence of variation of etching conditions on the sensitivity of PADC detectors with a new evaluation method.

At the Paul Scherrer Institut, a personal neutron dosimetry system based on chemically etched poly allyl diglycol carbonate (PADC) detectors and an automatic track counting (Autoscan 60) for neutron dose evaluations has been in routine use since 1998. Today, the hardware and the software of the Autoscan 60 are out of date, no spare components are available anymore and more sophisticated image-analysis systems are already developed. Therefore, a new evaluation system, the 'TASLIMAGE', was tested thoroughly in 2009 for linearity, reproducibility, influence of etching conditions and so forth, with the intention of replacing the Autoscan 60 in routine evaluations. The TASLIMAGE system is based on a microscope (high-quality Nikon optics) and an ultra-fast three-axis motorised control for scanning the detectors. In this paper, the TASLIMAGE system and its possibilities for neutron dose calculation are explained in more detail and the study of the influence of the variation of etching conditions on the sensitivity and background of the PADC detectors is described. The etching temperature and etching duration were varied, which showed that the etching conditions do not have a significant influence on the results of non-irradiated detectors. However, the sensitivity of irradiated detectors decreases by 5 % per 1°C when increasing the etching temperature. For the variation of the etching duration, the influence on the sensitivity of irradiated detectors is less pronounced.

[The effect of timolol and dipivalyl-epinephrine in the treatment of the elevated intraocular pressure (author's transl)]. / Timolol und Adrenalindipivalat bei der Behandlung des erhöhten intraocularen Druckes.

Twenty-seven patients with ocular hypertension or open angle glaucoma were tested to see if, and to what extent, timolol and dipivalyl-epinephrine produced a supplementary reduction of intraocular pressure. In a shortterm study, 14 patients were tested with timolol (0.1%) and dipivalyl-epinephrine (0.25%). Simultaneous application of both substances produced a statistically more significant reduction of intraocular pressure than either timolol (0.1%) or dipivalyl-epinephrine (0.25%) alone. In 13 patients a comparison was made between patients who received both timolol (0.25%) and dipivalyl-epinephrine (0.1%) bis x and patients who received only timolol (0.25%) bis x over a period of 6, 9 and 12 weeks. Both substances used in combination produced a statistically more significant reduction in intraocular pressure than timolol (0.25%) bis x alone. The simultaneous application of an alpha and beta-adrenergic agonist and beta-adrenergic antagonist is not contradictory. The results are discussed on the basis of the mode of action of the applied substances.

[Metipranolol 0.1% and pilocarpine 2% as a fixed combination compared to each substance alone in the treatment of glaucoma. A controlled, randomized clinical study comparing the intraindividual effects and tolerance]. / Metipranolol 0,1% und Pilokarpin 2% als fixe Kombination im Vergleich zu den Monosubstanzen in der Behandlung des Glaukoms. Eine kontrollierte, randomisierte klinische Studie zum intraindividuellen Wirkungs- und Verträglichkeitsvergleich.

A fixed combination of pilocarpine 2% and metipranolol 0.1% was found to have a better pressure-lowering effect than pilocarpine 2% alone or metipranolol 0.1% alone, as well as being tolerated well, both subjectively and objectively. In many cases only the fixed combination was successful in lowering intraocular pressure to tolerable values.

[Experiences with the effectiveness and tolerance of guanethidine/dipivefrin-AT in the treatment of increased intraocular pressure]. / Erfahrungen über Wirksamkeit und Verträglichkeit von Guanethidin/Dipivefrin-AT bei der Behandlung des erhöhten Augeninnendruckes.

Investigation of the fixed combination of 0.5% guanethidine and 0.1% Dipivefrin demonstrated a good pressure-lowering effect (26.6% on average) as well as good subjective and objective tolerance. These findings justify its use as a preparation for lowering intraocular pressure.

[Changes in intraocular pressure during prostaglandin-induced abortion (author's transl)]. / Entwicklung des Augeninnendruckes bei prostaglandininduziertem Schwangerschaftsabbruch.

Experimental animal studies have shown that local or systemic application of prostaglandin produces an acute increase in intraocular pressure. Investigations were carried out in 17 women undergoing prostaglandin-induced abortions to determine whether any changes in IOP occurred. In 16 of the patients there was no evidence of any effect; in the other one there was a transient moderate pressure elevation.

PIP: Experimental animal studies have shown that local or systemic application of prostaglandin (PG) produces an acute increase in intraocular pressure (IOP). Investigations were carried out in 17 women undergoing PG-induced abortions to determine whether any changes in IOP occurred. In 16 of the patients, there was no evidence of any effects; in the other 1, there was a transient moderate pressure elevation. (author's)

[Beta-blocking treatment (author's transl)]. / Kardiovaskuläre und pulmonale Wirkungen bei lokaler Beta-Blockergabe.

Twenty-six patients with open-angle glaucoma were investigated to see if and to what extent topical treatment with timolol 0.5% produced systemic effects. All of the patient had contraindications to the systemic use of beta-blockers such as bradycardia, cardiac insufficiency and chronic obstructive pulmonary disease. In some patients the treatment had marked cardiovascular or pulmonary effects, especially in the group with chronic obstructive pulmonary disease.

[Timolol and acetazolamide in the treatment of increased intraocular pressure (author's transl)]. / Timolol und Acetazolamid bei der Behandlung des erhöhten intraocularen Druckes.

Twenty-four patients with open-angle glaucoma were tested to see if, and to what extent, timolol and acetazolamide produced a supplementary reduction of intraocular pressure. Twelve patients were treated with timolol eye drops, 0.5% b.d over a period of one week and then received one dose i.v. acetazolamide 250 mg which produced a statistically significant drop in intraocular pressure. Twelve patients with open-angle glaucoma who had been treated with acetazolamide 500 mg t.d.s. orally over a period of one week, received one drop of timolol 0.25% which produced a statistically significant additional effect. These results are discussed on the basis of the mode of action of the applied medications.

[The effect of timolol and parasympathicomimetica in the treatment of the elevated intraocular pressure (author's transl)]. / Timolol und Parasympathicomimetica bei der Behandlung des erhöhten intraocularen Druckes.

45 patients with ocular hypertension or open-angle glaucoma were tested to see if, and to what extent timolol and three other different parasympathicomimetics (pilocarpine 2%, carbachol 1.5%, aceclydine 2%) produced an supplementary reduction of the intraocular pressure. An equally marked, additional drop in eye pressure was achieved when patients who had been given timolol over an extended period of time, were additionally treated with one dose of pilocarpine 2% or carbachol 1.5%. Aceclydine 2% produced no statistically significant additional effect. Patients who had only been treated with pilocarpine 2% over an extended period of time and then were given one dose of timolol 0.25% produced a drop in eye presure more than double that of those patients who had been primarily treated with timolol and then received pilocarpine or carbachol. These results will be discussed on the basis of the mode of action of the applied medications.

[Anthocyanosides in the treatment of retinopathies (author's transl)]. / Anthocyanoside in der Behandlung von Retinopathien.

Thirty-one patients with various types of retinopathy were investigated with regard to the effect of anthocyanosides on the retinal vessels. Especially in patients with diabetic retinopathy, a positive influence on the permeability and tendency to hemorrhage was observed. The importance of internal treatment of the primary disease is pointed out.

[Guanethidine/dipivefrin and pilocarpine in the treatment of increased intraocular pressure]. / Guanethidin/Dipivefrin und Pilokarpin bei der Behandlung des erhöhten intraokularen Drucks.

Thirty patients with ocular hypertension or open-angle glaucoma were tested to see if, and to what extent, guanethidine/dipivefrin and pilocarpine produced a supplementary reduction in intraocular pressure. An equally marked additional lowering of pressure was achieved when patients who had been given guanethidine/dipivefrin over an extended period of time were additionally treated with one dose of pilocarpine 2%. The reduction in intraocular pressure was much more pronounced in patients who had been treated with pilocarpine 2% alone over an extended period of time, followed by a single dose of guanethidine/dipivefrin, than in those who had been treated first with guanethidine/dipivefrin and subsequently with pilocarpine.

[Local subjective tolerance of levobunolol and metipranolol in a double-blind comparative study in patients with increased intraocular pressure]. / Lokale subjektive Verträglichkeit von Levobunolol und Metipranolol in einer Doppelblind-Vergleichsstudie bei Patienten mit erhöhtem intraokularem Druck.

We evaluated the ocular comfort of 0.5% levobunolol hydrochloride and 0.6% metipranolol hydrochloride ophthalmic solutions in a randomized, double-masked, paired-comparison clinical trial. The drugs were given twice daily for 7 days to 16 patients with open-angle glaucoma or ocular hypertension. Patients rated comfort in terms of the severity of burning and/or stinging. For both drugs, the severity rating of ocular discomfort was low, averaging between 1 and 2 on a scale of 0-10. At initial and follow-up visits, the mean severity rating of burning or stinging with metipranolol was 2, slightly greater than the mean score of 1 with levobunolol. At 55% (26 of 47) of the patient visits, the patients rated levobunolol as more comfortable than metipranolol. Metipranolol (Betamann; Mann) was rated as more comfortable than levobunolol at only 9% (4 of 47) of the patient visits. The duration of burning and stinging was also rated as longer lasting with metipranolol treatment than with levobunolol (Vistagan; Pharma-Allergan) treatment. Although little ocular discomfort was reported for either drug, the majority of the patients tested rated levobunolol the more comfortable of the two drugs.