Clinical characterization of respiratory large droplet production during common airway procedures using high-speed imaging.

During the COVID-19 pandemic, a significant number of healthcare workers have been infected with SARS-CoV-2. However, there remains little knowledge regarding large droplet dissemination during airway management procedures in real life settings. 12 different airway management procedures were investigated during routine clinical care. A high-speed video camera (1000 frames/second) was for imaging. Quantitative droplet characteristics as size, distance traveled, and velocity were computed. Droplets were detected in 8/12 procedures. The droplet trajectories could be divided into two distinctive patterns (type 1/2). Type 1 represented a ballistic trajectory with higher speed large droplets whereas type 2 represented a random trajectory of slower particles that persisted longer in air. The use of tracheal cannula filters reduced the amount of droplets. Respiratory droplet patterns generated during airway management procedures follow two distinctive trajectories based on the influence of aerodynamic forces. Speaking and coughing produce more droplets than non-invasive ventilation therapy confirming these behaviors as exposure risks. Even large droplets may exhibit patterns resembling the fluid dynamics smaller airborne aerosols that follow the airflow convectively and may place the healthcare provider at risk.

[Management of tracheostomy patients during the COVID-19 pandemic: review of the literature and demonstration]. / Management von Patienten mit Tracheostoma während der COVID-19-Pandemie: Literaturüberblick und Demonstration.

BACKGROUND: Since emergence of the new coronavirus in China in December 2019, many countries have been struggling to control skyrocketing numbers of infections, including among healthcare personnel. It has now been clearly demonstrated that SARS-CoV­2 resides in the upper airways and transmits easily via aerosols and droplets, which significantly increases the risk of infection when performing upper airway procedures. Ventilated COVID-19 patients in a critical condition in the intensive care unit may require tracheotomy for long-term ventilation and to improve weaning. However, the risk of secondary infection of medical personnel performing subsequent tracheostomy care remains unclear. OBJECTIVE: This study aimed to evaluate the risk of droplet dispersion during tracheostomy tube change and overview tracheostomy tube change in COVID-19 patients. MATERIALS AND METHODS: The current literature was reviewed, quantitative and qualitative analyses of droplet formation during tracheostomy tube change in n = 8 patients were performed, and an overview of and checklist for tracheostomy tube change were compiled. RESULTS: This study demonstrates that tracheostomy tube change, in particular insertion of the new tube, may cause significant droplet formation. The aerosolization of particles smaller than 5 µm was not analyzed. CONCLUSION: Our data, together with the current literature, clearly emphasize that tracheostomy care is associated with a high infection risk and should only be performed by a small group of well-trained, maximally protected healthcare personnel.

Vaginal prevalence of human papillomavirus infections in women with uterovaginal aplasia before and after laparoscopically assisted creation of a neovagina: a prospective epidemiological observational study.

OBJECTIVE: To study vaginal as opposed to cervical human papillomavirus (HPV) acquisition with regard to true prevalence, HPV types, and the role of co-factors in virgins and after their sexual debut. DESIGN: Prospective epidemiological observational study. SETTING: University hospital specialised in genital malformations. POPULATION: Women diagnosed with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and undergoing neovaginoplasty between November 2011 and July 2017. METHODS: This is a prospective study including 186 women with MRKHS before and after sexual debut. MAIN OUTCOME MEASURES: Conventional vaginal cytology and different HPV tests were performed at surgery and during routine gynaecological follow-up 1, 3, 6 and ≥ 11 months after surgery and risk factors were documented. RESULTS: The mean age of all women at surgery was 20.1 years (SD 5.4), mean body mass index (BMI) was 22.1 kg/m2 (SD 4.6). In 83 vaginal samples from 41 different women at least one of the HPV tests was positive. Thirty-three different HPV types were detected. The prevalence of 41/186 = 22.0% as well as type distribution are comparable with those found in a young German female population. The overall rate of acquisition was clearly associated with sexual activity and smoking habits. Out of 367 Papanicolaou smears only six were abnormal with Pap IIID (MN II) and no obvious vaginal lesion was detected. CONCLUSIONS: Vaginal HPV prevalence and HPV types in previously virgin women after creation of a neovagina are not different from the acquisition of cervical infections in the general population and is clearly associated with sexual activity and with smoking habits. However, abnormal Papanicolaou smears are rarely seen. TWEETABLE ABSTRACT: Vaginal HPV prevalence after creation of a neovagina is similar to that on the cervix in the general population.

Evaluation of the safety in dogs of long-term, daily oral administration of capromorelin, a novel drug for stimulation of appetite.

The objective of the study was to evaluate the safety of capromorelin, a ghrelin agonist that stimulates appetite and causes increased body weight and the release of growth hormone (GH). Beagle dogs (n = 32) received either oral placebo or 0.3, 7, or 40 mg/kg capromorelin once daily for 12 consecutive months. Safety was evaluated by physical examinations, including ECG and ophthalmic examinations, and comprehensive clinical pathology. Serum levels of capromorelin, GH, and insulin-like growth factor 1 (IGF-1) were measured periodically. Necropsies and histopathological evaluations were performed at study termination. As expected, GH and IGF-1 levels were mildly increased in capromorelin-treated dogs. Adverse events were limited to mild emesis and loose stools in all groups and excess salivation among some dogs receiving higher capromorelin doses. Clinical pathology testing was generally normal, although blood lipids and alkaline phosphatase levels were moderately increased among dogs receiving capromorelin. Treated dogs had slightly longer post-treatment PR intervals seen on ECG, but with no changes in cardiac histopathology. Postmortem findings were normal. Drug-related increases in liver weight were linked to overall increases in body weight. Capromorelin was well tolerated in dogs at daily doses up to 40 mg/kg for 12 months, demonstrating a wide safety margin.

A Prospective, Randomized, Masked, Placebo-Controlled Clinical Study of Capromorelin in Dogs with Reduced Appetite.

BACKGROUND: Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE® , Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite. HYPOTHESIS/OBJECTIVES: Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose. ANIMALS: A total of 244 client-owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis. METHODS: In this prospective, randomized, masked, placebo-controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations. RESULTS: Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin-treated dogs increased compared to placebo-treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P < .001). Adverse reactions occurring in >5% of either group were diarrhea and vomiting. CONCLUSIONS AND CLINICAL IMPORTANCE: Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.

In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti-Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats.

BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This study describes the design and characterization of a fully felinized anti-NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self-resolving, acute inflammation model were investigated in cats. ANIMALS: Thirty-eight cats at a research colony at Charles River Laboratories, Ireland. METHODS: Felinized anti-NGF mAb, NV-02, was produced using a complementary DNA (cDNA)-based method (PETization). Purified NV-02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin-induced inflammatory pain. RESULTS: Anti-NGF mAb, NV-02 neutralized NGF with high affinity and potency and did not bind complement. NV-02-administered SC had a plasma half-life of 7-15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV-02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: The high affinity, long plasma half-life, safety, and analgesic efficacy of felinized anti-NGF mAb (NV-02) support further investigation of the analgesic potential of this antibody in the cat.

A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis.

BACKGROUND: This study evaluated the effectiveness and safety of grapiprant for treatment of pain in dogs with osteoarthritis (OA). HYPOTHESIS/OBJECTIVES: Grapiprant will relieve pain as measured by the owner's and veterinarian's evaluation of pain in dogs with OA. Another objective was evaluation of the safety of grapiprant. ANIMALS: Two hundred and eighty-five client-owned dogs with OA were enrolled and treated with grapiprant or placebo with 262 cases (N = 131 in each group) evaluable for the effectiveness analysis. METHODS: In this prospective, randomized, masked, placebo-controlled study dogs were treated daily with grapiprant (2 mg/kg) per OS or placebo. Owners completed an evaluation using the Canine Brief Pain Inventory (CBPI) on days 0, 7, 14, 21, and 28. Success was defined as improvement in the CBPI. Veterinary assessments were made on screening and days 14 and 28. Safety was evaluated by physical examination, evaluation of clinical pathology results, and owner observations. RESULTS: Grapiprant treatment improved pain compared to placebo on day 28 (48.1 and 31.3% treatment successes respectively; P = .0315). The pain interference score (PIS) and pain severity score (PSS) improved in the grapiprant group compared to placebo (P = .0029 and 0.0022, respectively). Veterinary assessments were significantly better in the grapiprant-treated dogs (P = .0086). Grapiprant generally was well tolerated, but a higher percentage of treated dogs (17.02%) had occasional vomiting as compared to the placebo group (6.25%). CONCLUSIONS AND CLINICAL IMPORTANCE: Grapiprant is an effective treatment for alleviation of pain in dogs with OA, and represents a modality of treatment that may be better tolerated than current options.

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG.

Outcomes after implementation of a multimodal standard care pathway for laparoscopic colorectal surgery.

BACKGROUND: The aim of the study was to assess which aspects of an enhanced recovery programme are associated with better outcomes following laparoscopic colorectal surgery. METHODS: A database of laparoscopic colorectal procedures performed in 2011 was reviewed. Elements of the enhanced recovery programme and compliance were evaluated for short-term (30-day) outcomes. Individual elements included gabapentin, celecoxib, intrathecal analgesia, diet, postoperative fluids, and paracetamol/non-steroidal anti-inflammatory drug pain management. RESULTS: Five hundred and forty-one consecutive procedures were included. Compliance with the enhanced recovery programme elements ranged from 82.4 to 99.3 per cent. Median length of hospital stay was 3 (i.q.r. 2-5) days, with 25.9 per cent of patients discharged within 48 h. Patients without complications had a median length of stay of 3 (i.q.r. 2-4) days if compliant and 3 (3-5) days if not (P < 0.001). Low oral opiate intake (oral morphine equivalent of less than 30 mg) (odds ratio (OR) 1.97, 95 per cent confidence interval 1.29 to 3.03; P = 0.002), full compliance (OR 2.36, 1.42 to 3.90; P < 0.001) and high surgeon volume (more than 100 cases per year) (OR 1.50, 1.19 to 1.89; P < 0.001) were associated with discharge within 48 h. Compliance with the elements of oral intake and fluid management in the first 48 h was associated with a reduced rate of complications (8.1 versus 19.6 per cent; P = 0.001). Median oral opiate intake was 37.5 (i.q.r. 0-105) mg in 48 h, with 26.2 per cent of patients receiving no opiates. CONCLUSION: Compliance with an enhanced recovery pathway was associated with less opiate use, fewer complications and a shorter hospital stay.

Impact of bias in crown-rump length measurement at first-trimester screening for trisomy 21.

OBJECTIVE: To assess the repeatability of crown-rump length (CRL) measurement and examine the effect of its over- and underestimation on first-trimester combined screening. METHODS: Intra- and interoperator repeatability of CRL measurement at 11-13 weeks of gestation was assessed in 124 cases by two operators. Raw data were transformed into gestational age and intra- and interoperator repeatability was evaluated by within-operator standard deviation (SD) and the SD of differences in measurements between both operators. Modeling techniques were used to assess the impact of CRL measurement error on general population screening and on the operator-specific screening performance. The impact of errors in CRL measurement were investigated by simulating fetal nuchal translucency (NT) measurements and multiple of the median (MoM) values for pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks and 9 weeks of gestation, and adding to or subtracting from each CRL value up to 10 mm and recalculating patient-specific risks. RESULTS: Within-operator SD of the CRL measurement was 1.27 days of gestation. The SD of the differences in CRL measurement between operators was 1.37 days of gestation. Both intra- and interoperator 95% limits of agreement were around ± 5 mm. In general population-based screening, a CRL measurement error SD of 5 mm accounts for an estimated 5% of the SD of log MoM PAPP-A and less than 1% of the SD of log MoM free ß-hCG. Modeling the effect of removing this measurement error on overall screening performance showed a minimal impact. For a risk cut-off of 1 in 100, the benefit in terms of overall screening performance would be an increase in detection rate of about 1% and a reduction in false-positive rate of less than 0.1%. With regard to the operator-specific screening performance, a consistent 5-mm underestimation of CRL reduces the detection rate from 84% to 79% and the false-positive rate from 2.4% to 1.2%. With a consistent 5-mm overestimation the rates would be 88% and 5.6%, respectively. CONCLUSION: The impact of the interoperator variability in CRL measurement on patient-specific risk needs to be taken into account when interpreting first-trimester screening results. A systematic under- or overestimation of CRL should be avoided.

Real-time Nyquist pulse generation beyond 100 Gbit/s and its relation to OFDM.

Nyquist sinc-pulse shaping provides spectral efficiencies close to the theoretical limit. In this paper we discuss the analogy to optical orthogonal frequency division multiplexing and compare both techniques with respect to spectral efficiency and peak to average power ratio. We then show that using appropriate algorithms, Nyquist pulse shaped modulation formats can be encoded on a single wavelength at speeds beyond 100 Gbit/s in real-time. Finally we discuss the proper reception of Nyquist pulses.

Assessing the invasiveness of NOTES perforated viscus repair: a comparative study of NOTES and laparoscopy.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) repair of perforated peptic ulcers may decrease surgical invasiveness and improve patient outcomes. METHODS: Full thickness gastrotomy was created laparoscopically in swine followed by soilage time. Repair proceeded with a laparoscopic (n = 14) or the NOTES (n = 14) approach. For NOTES repair, the omentum was endoscopically pulled into the gastric lumen and clipped. Intraoperative and postoperative parameters were recorded, including arterial blood gas (ABG) analysis and serum samples for white blood cell (WBC), TNF-α, IL-1, and IL-6 analysis. RESULTS: Twenty-four of 28 animals thrived to study completion. NOTES repair could not be accomplished in one animal. At necropsy, all repairs were intact. Blood pressure was equivalent between groups. Pulse examined during the last 30 min of each procedure revealed a slightly higher mean pulse in the animals undergoing NOTES procedures (NOTES, 102 ± 28; laparoscopy, 83 ± 24). ABG obtained at the conclusion of the procedure revealed a pH of 7.47 in NOTES animals and 7.43 in the laparoscopy animals (p = 0.06), a change from baseline in both groups. The final pCO(2) was lower in the NOTES group (NOTES, 40.62; laparoscopy, 47.49, p = 0.03). WBC counts were comparable on postoperative day (POD) 1 (NOTES, 21.1; laparoscopy, 19.0; p = 0.49). Mean TNF-α serum levels were equivalent at all time points between groups; however, TNF-α varied significantly from baseline to POD 7 (p = 0.002). CONCLUSION: NOTES omental repair appears comparable to that of laparoscopy. The lower arterial pCO(2) at the conclusion of the NOTES procedure may be advantageous in critically ill patients.

Outcomes following surgery without radiotherapy for rectal cancer.

BACKGROUND: This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy. METHODS: This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board. RESULTS: Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow-up was 62 months. The 5-year rate of local recurrence was 4·3 per cent, disease-free survival 90·0 per cent and cancer-specific survival 91·5 per cent. Stage-specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3·6 versus 5·5 per cent; P = 0·321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis. CONCLUSION: Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit.

Case-matched series of enhanced versus standard recovery pathway in minimally invasive colorectal surgery.

BACKGROUND: Accelerated recovery pathways may reduce length of hospital stay after surgery but there are few data on minimally invasive colorectal operations. METHODS: An enhanced recovery pathway (ERP) was instituted, including preoperative analgesia, limited intravenous fluids and opiates, and early feeding. Intrathecal analgesia was administered as needed, but epidural analgesia was not used. The first 66 patients subjected to the ERP were case-matched by surgeon, procedure and age (within 5 years) with patients treated previously in a fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were compared. RESULTS: Hospital stay was shorter with the ERP than the FTP: median (interquartile range, i.q.r.) 3 (2-3) versus 3 (3-5) days (P < 0·001). A 2-day hospital stay was achieved in 44 and 8 per cent of patients respectively (P < 0·001). Patients in the ERP had a shorter time to recovery of bowel function: median (i.q.r.) 1 (1-2) versus 2 (2-3) days (P < 0·001). Thirty-day complication rates were similar (32 per cent ERP, 27 per cent FTP; P = 0·570). Readmissions within 30 days were more common with ERP, but the difference was not statistically significant (10 versus 5 patients; P = 0·170). Total hospital stay for those readmitted was shorter in the ERP group (18 versus 23 days). CONCLUSION: ERP decreased the length of hospital stay after minimally invasive colorectal surgery.

Real-time OFDM transmitter beyond 100 Gbit/s.

Real-time OFDM transmitters breaking the 100 Gbit/s barrier require high-performance, usually FPGA-based digital signal processing. Especially the Fourier transform as a key operation of any OFDM system must be optimized with respect to performance and chip area utilization. Here, we demonstrate an alternative to the widely adopted fast Fourier transform algorithm. Based on an extensive yet optimized use of pre-set look-up tables, our FPGA implementation supports fast reconfigurable channel equalization and switching times in the nanosecond range without re-loading any code. We demonstrate the potential of the concept by realizing the first real-time single polarization OFDM transmitter generating a 101.5 Gbit/s data stream by modulating 58 subcarriers with 16QAM.

Clinical Characteristics, Surgical Management and Adjuvant Therapy of Patients with Uterine Leiomyosarcoma: 27 Years of Experience.

Purpose: To review a single-center experience over a 27-year period in the management of uterine leiomyosarcoma (LMS) for insight into surgical practice, adjuvant therapy and clinical outcome. Material and Methods: This was a retrospective study of women with histologically proven uterine LMS who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained. Results: The study sample comprised 32 patients with uterine LMS. Primary surgical treatment consisted of total abdominal hysterectomy in 28 patients (88 %) and laparoscopic total hysterectomy in 4 patients (12 %). Lymph nodes were dissected and evaluated in 17 women (53 %); positive lymph nodes were present in 1 patient (6 %). A total of 17 patients (53 %) received adjuvant therapy. Median follow-up for disease-free survival (DFS) was 35.6 months and median DFS was 27.0 months for all patients. The median follow-up for overall survival (OS) was 51.3 months and the median OS was 28.0 months for our study group. The 5-year survival rate was 30 %. There was no significant difference in DFS (p = 0.76) and OS (p = 0.51) between patients who received adjuvant therapy and those who did not. Conclusion: Uterine LMS are rare and aggressive uterine neoplasms with high recurrence rates and metastatic potential. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with uterine LMS. Lymphadenectomy should be reserved for patients with clinically suspicious nodes.

Optically powered fiber networks.

Optically powered networks are demonstrated. Heterogeneous subscribers having widely varying needs with respect to power and band-width can be effectively controlled and optically supplied by a central of-fice. The success of the scheme relies both on power-efficient innovative hardware and on a novel low-energy medium access control protocol. We demonstrate a sensor network with subscribers consuming less than 1 microW average power, and an optically powered high-speed video link transmitting data at a bitrate of 100 Mbit/s.

[Clinical experience in the treatment of neovascular age-related macular degeneration with pegaptanib]. / Klinische Erfahrungen in der Anwendung von Pegaptanib bei der Behandlung der exsudativen altersabhängigen Makuladegeneration (AMD).

BACKGROUND: Intravitreal anti-VEGF therapy with Pegaptanib was effective in neovascular AMD in the VISION study. We report our experience with Macugen for the treatment of occult or minimally classic choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: 35 eyes of 35 patients with occult CNV or minimally classic CNV due to neovascular AMD not eligible for PDT were treated with intravitreal injection of 0.3 mg Pegaptanib. An average of 2.74 injections per patient was administered. Before, and every 3 months after treatment, visual acuity, intraocular pressure measurement, angiography and OCT examinations were performed. One month after treatment only visual acuity, intraocular pressure measurement, and OCT examinations were performed. Visual acuity measurements and an eye examination were done on the first and second day after injection, after 4-6 weeks and at months 3 and 6. RESULTS: Intravitreal Pegaptanib was well tolerated and we had no complications. Mean visual acuity was 0.38 +/- 0.23 at baseline, after one month 0.38 +/- 0.26, at 3 months it was 0.39 +/- 0.22 and at 6 months 0.41 +/- 0.26. OCT examinations showed a decrease in central retinal thickness from 277 microm to 254 microm. In 91.4 % of the eyes the visual acuity was stabilised or improved. No patient had an elevated intraocular pressure after 6 months. CONCLUSIONS: Intravitreal therapy with Pegaptanib was safe and effective. The majority of patients showed a stabilisation in all the assessed parameters. In clinical practice unselective VEGF inhibition should be considered carefully for patients with high cardiovascular risk profile or thromboembolic events in the history.

Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood.

BACKGROUND: Atopic eczema is characterized by Th2-dominant immunity with the cytokine interleukin 13 and the transcription factor GATA binding protein 3 playing a critical role. OBJECTIVES: We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema. METHODS: A birth cohort (n = 1456) was established on the Isle of Wight in 1989 and followed at the ages of 1 (n = 1167), 2 (n = 1174), 4 (n = 1218) and 10 years (n = 1373) to determine the prevalence of allergic disease including eczema. At 4 and 10 years, skin prick testing was performed. Whole blood samples (n = 923) were obtained at the 10-year assessment, stored frozen, and genotyped. Five polymorphisms from IL13 and seven from GATA3 were genotyped for this analysis. Repeated measurement analyses were conducted for the occurrence of eczema at ages 1, 2, 4 and 10 years. All analyses were adjusted for maternal and paternal eczema, low birth weight (< 2500 g), breastfeeding >or= 3 months and age. RESULTS: IL13 was not associated with childhood eczema. For GATA3, the single nucleotide polymorphism (SNP) rs2275806 (promoter region) showed an increased odds ratio for atopic eczema independent of whether the comparison group had a positive skin prick test. The SNP rs444762 (intron 3 region) was associated with atopic eczema in comparison with children without eczema. The increased relative risks remained significant after adjustment for multiple testing only for rs2275806 (P < 0.05). CONCLUSIONS: A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema.