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Objectives : To compare intraocular lens (IOL) position and refractive outcomes between eyes that underwent sole phacoemulsification with those that underwent combined 25-gauge phacovitrectomy with a plate-haptic toric IOL implantation. Methods : This retrospective study included 60 eyes of 60 patients. Of these, 30 eyes underwent 25-gauge phacovitrectomy, while the other 30 eyes received phacoemulsification alone. In both groups, a plate-haptic toric intraocular lens (AT Torbi 709M, Carl Zeiss Meditec AG) was implanted. The main outcome measures were the refractive outcome, the refraction prediction error (PE), the difference in the postoperative anatomical lens position (ALP) change, and rotational stability. Results : The mean spherical equivalent decreased considerably from -2 ± 4.4 diopters (D) to -0.6 ± 1.4 D after phacovitrectomy ( p = 0.05) and -0.7 D ± 5.5 D to -0.1 ± 1.1 D after phacoemulsification ( p = 0.5). The prediction error (PE) was comparable between the two groups for all formulas (Haigis-T: p = 0.8, Barrett TK Toric: p = 0.8, Z CALC: p = 0.7). No significant difference in absolute ALP change and postoperative rotational stability was observed between the phacovitrectomy and phacoemulsification group (1.4 mm vs. 1.4 mm, p = 0.96; 2.9° vs. 2.1°, p = 0.5). Conclusions : The implantation of plate-haptic toric IOLs in the combined phacovitrectomy group resulted in refraction and IOL positioning outcomes comparable to those in the phacoemulsification-only group.

Purpose: To evaluate the long-term outcomes of patients with non-infectious uveitis treated with 0.19 mg fluocinolone acetonide insert (FAi) for up to 36 months in clinical practice., Methods: A retrospective study conducted at a single uveitis center., Results: Fifty eyes of 39 patients were included. Mean best corrected visual acuity (BCVA) and central retinal thickness (CRT) remained stable until month 36 after FAi implantation (61.04 vs. 70.25 letters and 370.8 vs. 332.5 µm, respectively). The recurrence rate was 34% (17 eyes) after 36 months, of which 82% (14 eyes) received high-dose corticosteroids before FAi. Mean intraocular pressure (IOP) remained unchanged (13.38 vs. 15.74 mmHg), while most phakic eyes (13 of 14 eyes) required cataract surgery., Conclusions: We show that FAi effectively prevents recurrences of non-infectious uveitis for up to three years in clinical practice, comparable with randomized clinical trials. Patients who received high-dose corticosteroids before FAi have an increased risk for early recurrence and should be considered for scheduled re-treatment.

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor ( SNAI1/2 ) and Vimentin ( VIM ) while decreasing Cadherin ( CDH1 ), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet's membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance.

Accurate assessment of corneal curvatures using frequency domain optical coherence tomography (OCT) with galvanometer scanners remains challenging due to the well-known scan field distortion. This paper presents an algorithm and software for correcting the distortion using only two simple measurements in which a readily available standard sphere is positioned in different depths in front of the OCT scanner. This offers a highly accessible and easily reproducible method for the field distortion correction (FDC). The correction was validated by measuring different spherical phantoms and conducting corneal curvature measurements of ex vivo porcine corneas using a commercial spectral-domain OCT system and a clinically approved swept-source OCT as a reference instrument. Thus, the error in radius measurements of spherical phantoms was reduced by >90 % and astigmatism by >80 % using FDC. In explanted porcine eyes, the error in astigmatism measurements with the Telesto was reduced by 75% for power and 70% for angle. The best fitting sphere radius was determined up to a deviation of 0.4% from the Anterion. This paper describes a correction algorithm for OCT immanent distortion that is applicable to any scanning OCT setup and enables precise corneal curvature measurements. The MATLAB software for the FDC is publicly available on GitHub.

Background and Objectives: Quality of life (QoL) has never been assessed in previous illicit users of androgens years following androgen cessation. Therefore, the objective of this study was to assess QoL in previous illicit androgen users compared with current illicit androgen users and controls who had never used androgens., Methods: Cross-sectional study including men involved in recreational strength training grouped according to their history of androgen use. We used the RAND Short-Form-36 questionnaire to assess physical and mental health-related QoL., Results: We included 77 previous and 118 current androgen users and 39 healthy nonusers. The mean (SD) age of all participants was 33 (8) years. The elapsed duration since androgen cessation, geometric mean (95% CI), was 2.0 (1.5-2.6) years in former users. Median (25th-75th percentiles) serum total testosterone was lower in former users than controls, 14 (11-17) vs 19 (16-21) nmol/L, P < .001. Previous users displayed lower mean (SD) across both mental and physical (PCS) component summary scores, 48 (10) vs 54 (4) (P = .004) and 48 (9) vs 53 (3) (P = .002) compared with controls.Using multivariate linear regressions, evaluating physical and mental component scores as dependent variables, lower serum total testosterone, longer duration since androgen cessation, study recruitment from an endocrine outpatient clinic, and established chronic diseases were all independently associated with reduced QoL in previous users, P < .05., Conclusions: Previous illicit androgen users exhibited reduced QoL 2 years after androgen discontinuation, which may be a persistent condition., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To evaluate the postoperative intraocular lens (IOL) rotational stability and residual refractive astigmatism following combined 25-gauge vitrectomy and cataract surgery with implantation of a plate haptic toric IOL., Methods: In this retrospective case series, 32 eyes of 32 patients underwent a combined 25-gauge vitrectomy and phacoemulsification for vitreoretinal diseases and cataract with regular corneal astigmatism of at least 1 diopter (D). A plate haptic toric IOL (AT Torbi 709M, Carl Zeiss Meditec AG) was implanted in all eyes. The outcome measures were rotational stability and refractive astigmatism up to 6mo postoperatively as well as the best corrected visual acuity (BCVA)., Results: Preoperative refractive astigmatism was 2.14±1.17 D, which was significantly reduced to 0.77±0.37 D six to eight weeks postoperatively and remained stable throughout the observation period (0.67±0.44 D at three months and 0.75±0.25 D at six months; for all groups: P <0.0001 compared to baseline). BCVA improved significantly from 0.36±0.33 logMAR preoperatively to 0.10±0.15 logMAR following surgery ( P =0.02). Mean IOL axis deviation from the target axis was 3.4°±2.9° after six to eight weeks and significantly decreased over time (2.4°±2.6° six months after surgery; P =0.04). In one patient IOL, re-alignment was performed., Conclusion: Corneal astigmatism is significantly reduced following combined 25-gauge vitrectomy and cataract surgery. The plate haptic toric IOL position and axis remain stable during the observation period of six months., (International Journal of Ophthalmology Press.)

Purpose: To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi., Methods: A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation., Results: In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: - 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 μm, difference 53.57 μm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference - 1.92; 95% CI: - 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted., Conclusion: We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity., (© 2022. The Author(s).)

Background: Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Older adults represent an understudied and growing TBI population. Current Brain Trauma Foundation guidelines support prophylactic antiseizure medication (ASM) administration to reduce the risk of early posttraumatic seizures (within 7 days of injury) in patients with severe TBI. Whether ASM decreases mortality or early seizure risk in this population remains unclear. This study addresses the knowledge gap regarding the impact of ASM administration on the risk of seizure or mortality after TBI in patients more than 65 years of age., Methods: This retrospective cohort study used a publicly available data set from the Medical Information Mart for Intensive Care-III from the Massachusetts Institute of Technology. Our cohort included patients 65 years or older with a primary exposure of early ASM administration with TBI resulting in an intensive care unit (ICU) admission in a level I trauma center from 2001 to 2012. A double-robust inverse propensity scale weighted model on the basis of proportional hazard and logistic regression models was created to assess the association between ASM administration and risk of death within 7 days of admission to the ICU. Secondary outcomes included 30-day mortality and 1-year mortality, early posttraumatic seizures, ICU length of stay, and hospital length of stay., Results: Of 1145 patients 65 years or older with TBI admitted to an ICU, 783 (68.4%) received ASM within the first 24 h. Patients meeting inclusion criteria were predominantly white (83.8%) and were male (52.3%), with a median (interquartile range) age of 81 (74-86) years. TBI severity, classified by Glasgow Coma Score, was predominantly mild (71.2%), followed by moderate (16.8%) and severe (11.3%). Patients who received ASM were less likely to have died at 7 days (adjusted death hazard ratio [HR] = 0.48 [95% confidence interval {CI} 0.28-0.88], P = 0.005), at 30 days (adjusted HR 0.67 [95% CI 0.45-0.99], P = 0.045), and at 1 year (adjusted HR 0.72 [95% CI 0.54-0.97], P = 0.029). Groups were not different in regard to seizure (adjusted seizure odds ratio 1.18 [95% CI 0.61-2.26]) compared with those who did not receive ASM., Conclusions: Early ASM administration was associated with reduced mortality at 7 days, 30 days, and 1 year but did not decrease the risk of early seizures among older adults who presented with TBI at an ICU. This benefit was observed in mild, moderate, and severe TBI assessed by Glasgow Coma Score on presentation among patients 65 years old and older and suggests broader recommendations for the use of ASM in older adults who present with TBI of any severity at an ICU., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Physical and social distancing recommendations aimed at limiting exposure during the COVID-19 pandemic have forced residency programs to increasingly rely on videoconferencing and web-based resources., Objective: In this pilot study, we aimed to explore the effects of the COVID-19 pandemic on residency training experience, and to delineate the perceived barriers to the successful implementation of web-based medical education., Methods: A 19-item survey was compiled and distributed electronically using Qualtrics. This anonymous survey included information on the training level of each resident, their participation in formal didactics before and during the pandemic, and their perception of the ease and limitations of virtual didactics. The resident's opinions on specific educational resources were assessed, and the effectiveness of new delivery methods on resident engagement and learning was examined., Results: Thirty anesthesiology residents were surveyed, 19 of whom agreed to participate in the pilot study. One participant with incomplete responses was excluded, yielding a final cohort of 18 respondents. Most residents (56%, 10/18) reported that the COVID-19 pandemic negatively affected their residency training. The time spent on didactic training and independent studies was, nevertheless, not affected by the pandemic for 90% (16/18) of respondents. Nonetheless, 72% (13/18) of residents were less engaged during virtual lectures in comparison to in-person didactics. Important limitations included distraction from the physical environment (67%, 12/18), internet instability (67%, 12/18), less obligation to participate (44%, 8/18), technical difficulty and unmuted microphones (33%, 6/18, each), and people speaking over each other (28%, 5/18). Despite these limitations, most residents stated that they would like to keep a combination of virtual didactics including live Zoom lectures (56%, 10/18), prerecorded web didactics (56%, 10/18), and virtual ground rounds via Zoom (50%, 9/18) as the "new normal.", Conclusions: Despite important limitations listed in this report, anesthesia residents would like to keep a combination of virtual lectures and presentations as the new normal after the COVID-19 pandemic., (©Ala Nozari, Shivali Mukerji, Ling-Ling Lok, Qingrou Gu, Lauren Buhl, Sanjay Jain, Rafael Ortega. Originally published in JMIR Medical Education (https://mededu.jmir.org), 31.03.2022.)

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the lung epithelium are thought to be critical drivers of disease progression, contributing to fibroblast activation, extracellular matrix remodeling, and subsequently loss of lung architecture and function. To date, Pirfenidone and Nintedanib are the only approved drugs known to decelerate disease progression, however, if and how these drugs affect lung epithelial cell function, remains largely unexplored., Methods: We treated murine and human 3D ex vivo lung tissue cultures (3D-LTCs; generated from precision cut lung slices (PCLS)) as well as primary murine alveolar epithelial type II (pmATII) cells with Pirfenidone or Nintedanib. Murine 3D-LTCs or pmATII cells were derived from the bleomycin model of fibrosis. Early fibrotic changes were induced in human 3D-LTCs by a mixture of profibrotic factors. Epithelial and mesenchymal cell function was determined by qPCR, Western blotting, Immunofluorescent staining, and ELISA., Results: Low μM concentrations of Nintedanib (1 μM) and mM concentrations of Pirfenidone (2.5 mM) reduced fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and human 3D-LTCs as well as pmATII cells. Notably, Nintedanib stabilized expression of distal lung epithelial cell markers, especially Surfactant Protein C in pmATII cells as well as in murine and human 3D-LTCs., Conclusions: Pirfenidone and Nintedanib exhibit distinct effects on murine and human epithelial cells, which might contribute to their anti-fibrotic action. Human 3D-LTCs represent a valuable tool to assess anti-fibrotic mechanisms of potential drugs for the treatment of IPF patients.

Purpose: The purpose of the study was to assess the emergency department (ED) providers' interest and satisfaction with ED CT result reporting before and after the implementation of a standardized summary code for all CT scan reporting., Materials and Methods: A summary code was provided at the end of all CTs ordered through the ED from August to October of 2016. A retrospective review was completed on all studies performed during this period. A pre- and post-survey was given to both ED and radiology providers., Results: A total of 3980 CT scans excluding CTAs were ordered with 2240 CTs dedicated to the head and neck, 1685 CTs dedicated to the torso, and 55 CTs dedicated to the extremities. Approximately 74% CT scans were contrast enhanced. Of the 3980 ED CT examination ordered, 69% had a summary code assigned to it. Fifteen percent of the coded CTs had a critical or diagnostic positive result., Conclusions: The introduction of an ED CT summary code did not show a definitive improvement in communication. However, the ED providers are in consensus that radiology reports are crucial their patients' management. There is slightly increased satisfaction with the providers with less than 5 years of experience with the ED CT codes compared to more seasoned providers. The implementation of a user-friendly summary code may allow better analysis of results, practice improvement, and quality measurements in the future.

A care plan provides a patient, family, or community picture and outlines the care to be provided. The Health Level Seven Consolidated Clinical Document Architecture (C-CDA) Release 2 Care Plan Document is used to structure care plan data when sharing the care plan between systems and/or settings. The American Nurses Association has recommended the use of two terminologies, Logical Observation Identifiers Names and Codes (LOINC) for assessments and outcomes and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) for problems, procedures (interventions), outcomes, and observation findings within the C-CDA. This article describes C-CDA, introduces LOINC and SNOMED CT, discusses how the C-CDA Care Plan aligns with the nursing process, and illustrates how nursing care data can be structured and encoded within a C-CDA Care Plan.

We report our experimental results for linear analog optical links that use phase or frequency modulation and optical discrimination. The discriminators are based on two architectures: a cascaded MZI FIR lattice filter and a ring assisted MZI (RAMZI) IIR filter. For both types of discriminators, we demonstrate > 6 dB improvement in the link's third-order output intercept point (OIP3) over a MZM link. We show that the links have low second-order distortion when using balanced detection. Using high optical power, we demonstrate an OIP3 of 39.2 dBm. We also demonstrate 4.3dB improvement in signal compression.

We propose a novel energy-efficient coherent-optical OFDM transmission scheme based on hybrid optical-electronic signal processing. We demonstrate transmission of a 0.26-Tb/s OFDM superchannel, consisting of 13 x 20-Gb/s polarization-multiplexed QPSK subcarrier channels, over 400-km standard single-mode fiber (SSMF) with BER less than 6.3x10(-4) using all-optical Fourier transform processing and electronic 7-tap blind digital equalization per subchannel. We further explore long-haul transmission over up to 960 km SSMF and show that the electronic signal processing is capable of compensating chromatic dispersion up to 16,000 ps/nm using only 15 taps per subchannel, even in the presence of strong inter-carrier interference.

We propose that the optical OFDM technique using all optical discrete Fourier transform (DFT) has potential as a viable alternative for upgrading long-haul optical transmission systems towards 100-Gb/s. We demonstrate transmission of 35-Gb/s (7 x 5 Gb/s NRZ-OOK) all-optical OFDM signal over ~2000-km dispersion-managed span without using tunable dispersion compensation and time gating. We achieve bit error ratio of 1.2x10(-3) (7x10(-3)) for transmission over 1980-km (2310-km) all-EDFA amplified span consisting of standard single mode fiber (SSMF) and dispersion compensating fiber (DCF). We also study the nonlinear penalty impacting the all-optical OFDM transmission and discuss potential method for its mitigation., (© 2011 Optical Society of America)

We implement dispersion-tolerant and time-gating-free all-optical OFDM transmission using a photonic-integrated discrete Fourier transform (DFT) device. We show that 35-Gb/s OFDM data having near-unity spectral efficiency can be transmitted all-optically with 1-dB dispersion margin of ~1000 ps/nm. The passive-optical DFT circuit is implemented using multi-mode interference (MMI) couplers on a high index-contrast silica integrated-optic platform. We also propose a photonic DFT circuit based on an NxN MMI device capable of simultaneous channelization of OFDM signals into N subcarriers., (© 2011 Optical Society of America)

We propose a method for increased-speed all-optical XOR operation using semiconductor optical amplifiers. We demonstrate XOR and XNOR operations at 86.4 Gb/s using a pair of photonic-integrated semiconductor optical amplifier Mach-Zehnder interferometers.

Vitamin D status may affect risk of cancer. In a cross-sectional study with a nested case-control analysis, we determined whether risk of breast cancer is associated with prediagnostic plasma 25-hydroxyvitamin D (25OHD) levels and the effects of lifestyle characteristics known to influence vitamin D status on risk of breast cancer. We studied women without a prior history of breast cancer referred to a diagnostic mammography examination (n = 2,465). Cases were women diagnosed with an incident breast cancer (n = 142). Controls were women not diagnosed with a breast cancer matched to cases on age, menopausal status, and time of year of blood sampling (n = 420). Characteristics of cases and controls were assessed by a self-administrated questionnaire. Blood samples were collected prior to the diagnostic mammography examination. Cases had lower plasma 25OHD levels than controls. Compared with the lowest tertile of 25OHD levels, risk of breast cancer was significantly reduced among women in the highest tertile (relative risk, 0.52; 95% confidence interval, 0.32-0.85). Risk estimates were similar in women with an estrogen receptor-positive and estrogen receptor-negative breast cancer. Use of vitamin D supplements, sunbathing frequency, and fish intake was associated with 25OHD levels, but did not affect the risk of breast cancer. Accordingly, risk of breast cancer was inversely associated with 25OHD levels. Randomized controlled trials are warranted in order to assess whether a causal relationship exists.

We report a novel hybrid integrated optic device consisting of AlGaInAs/InP electroabsorption modulators and a four-arm silica-on-silicon planar lightwave circuit optical interferometer. The device is designed for generation of high spectral efficiency optical modulation formats. We demonstrate generation of 21.4 Gb/s quadrature phase shift keyed optical signals with electrical data drives of 2V(pp) amplitudes, achieving a bit error rate of 10(-9) with the required optical signal to noise ratio of ~18 dB in a 0.1 nm resolution bandwidth.

Aim: To report a case of a pheochromocytoma secreting vasoactive intestinal peptide (VIP)., Methods: We studied a 77-year-old woman who had suffered from persistent diarrhea and episodes of sweating and palpitations., Results: She had neither previous or current anamnesis of hypertension nor any known familial dispositions to endocrine diseases. Initially gastrointestinal investigations were carried out based on longstanding diarrhea with hypopotassemia, but radiological imaging revealed a unilateral adrenal mass. Biochemical testing showed increased levels of catecholamine and VIP, and (123)I-metaiodobenzylguanidine scintigraphy confirmed the adrenal origin as well as the diagnosis of a VIP-producing pheochromocytoma. The patient underwent surgical removal of the tumor which led to relief of symptoms and normalized laboratory values., Conclusion: This case report focuses on the protean mode of presentation seen in pheochromocytomas as well as their capacity to produce several neuropeptides, ultimately intensifying the need for early examination for this condition despite unrelated symptoms., (Copyright 2008 S. Karger AG, Basel.)

The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours (10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

Poly-alpha 2-8 sialic acid (PSA), attached to the neural cell adhesion molecule, is a permissive determinant for numerous morphogenetic and neural plasticity processes, making it a potential therapeutic target. Here, using a monoclonal antibody specific for PSA, we screened a phage-display library and identified two cyclic nine-amino acid peptides (p1, p2) that are PSA epitope analogues. We evaluated their bioactivity in vitro and in vivo. In culture, micromolar concentrations of the peptides promoted axon growth, defasciculation, and migration of neural progenitors. When injected into developing chicken retina, the peptides modified the trajectory of retinal ganglion cell axons. Moreover, they enhanced migration of grafted neuroblasts in mouse brain. These effects were selective and dependent upon the presence of PSA on transplanted cells. Our results demonstrate the feasibility and therapeutic potential of enhancing PSA biological activity.

Aims: This study set out to identify any undesirable consequences of legislative change in the organization of the treatment of problem drug users (PDUs), which aimed to combine their social and medical care., Method: The method used was a register-based three-year follow-up prevalent cohort study., Results: On 1 January 1996, the law was changed to allocate unambiguous and undivided responsibility for the combined social and medical care of PDUs in Denmark. The main objective of the legislative change was to move PDUs from treatment by general practitioners (GPs) and at private clinics to treatment institutions under the control of the counties. The possibility remained that medical treatment could, however, continue to be given by GPs or private clinics, based on specific agreements. The study showed that at the end of the period, 31 December 1998, two-thirds remained in treatment at private clinics or at GP surgeries. During the period only 8% of users were at some time without methadone treatment; 2% remained without methadone treatment throughout the study period., Conclusion: The transition from GPs and private clinics to the county treatment centres went smoothly. The number of PDUs in MMT (methadone maintenance treatment) in the city of Copenhagen increased in the period 1995 to 1998. The average quantity of methadone given to the cohort increased during these years from 72 mg per day to 92 mg per day. The legislative change therefore did not result in a higher threshold for treatment or a more restrictive prescription of methadone. No adverse effect on crime, hospital admissions, or death could be attributed to the legislative change in treatment organization.

Imatinib is a potent drug used in treatment of chronic myeloid leukaemia (CML). It acts by inhibition of the CML-specific p210 BCR-ABL tyrosine kinase, but also blocks other pathways such as platelet-derived growth factor (PDGF) and c-kit receptor signalling. Clinical trials have confirmed the efficacy of imatinib, which has toxic effects in cells that express BCR-ABL. Side-effects, although frequent, are generally mild and include superficial oedema and fluid retention. Here, we describe two patients with cerebral oedema, which in one patient was fatal. The pathophysiological mechanisms remain unknown, although the drug could act through inhibition of the PDGF receptor.

With the aim of producing unique targets for malignant cells we have identified peptide ligands for the clonal surface immunoglobulin isolated from the B cells of a chronic lymphocytic leukaemia (CLL) patient. The peptides were identified from random-peptide phage-display libraries. The obtained ligands bound specifically to the surface of the target lymphocytes as well as to clonal immunoglobulin in lysate from the same cells. Peptide-based antigen mimotopes may have a future use in targeted therapy of CLL and other B-cell-derived malignancies displaying surface immunoglobulin.

We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M-proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage-displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.

A total of 911 Danish children under 15 years of age were treated for an intracranial tumour in the 25-five year period 1960-1984. All cases were followed up to the end of 1994 or to emigration or death if one of these came sooner. The mean annual incidence was 32.5 per million children with a slight increase over the 25 years. The male/female ratio was 1.15 and close to the M/F ratio for the entire Danish population of children. Of the tumours, 46% were located in the supratentorial and 54% in the infratentorial compartment, and 94% were verified histologically. In order of frequency the most common types were astrocytomas (all grades, 35%), medulloblastomas (20%), ependymomas (14%), and craniopharyngiomas (5%). Total removal of the tumour was performed in 277 and partial removal, including biopsy, in 490 children. In 57 patients a shunt operation only was performed, and 87 children did not have an operation or died before the correct diagnosis was established. Radiotherapy was administered in 55%. The outcome depended on extent of removal, radiation, location and histology of the tumour. Most (784 or 86%) of the children survived more than 1 month after diagnosis or operation, and 353 children (39% of the whole series, 47% of those alive more than 1 month after diagnosis) were alive at follow-up. Of the survivors 29% had a tumour in the supratentorial midline, 26% one in the lateral part of the supratentorial area, 31% a cerebellar tumour and 13% a IV ventricle tumour. It was possible for 66% of the survivors with supratentorial and 90% of those with infratentorial tumours to lead a normal life. The long-term prognosis was especially good for children with cerebellar and supratentorial astrocytomas and optic chiasma tumours. Children with juvenile cerebellar astrocytoma had the best prognosis: 90% were alive at the end of the follow-up period, as against 20% of those with medulloblastoma and 6% of those with glioblastoma. A comparison of the data from the present series and from a similar Danish series of intracranial tumours in 533 children seen in the years 1935-1959 shows no significant differences in location or histology, a slight increase in annual incidence, and improved survival rates during the 50 years in question.

Immunoreactivity of the cytokine IL-10 has been investigated in situ in mycosis fungoides (MF). Expression of IL-10 was detected using immunohistochemistry in skin biopsies (n = 8) and T-cell lines (n = 2) from mycosis fungoides patients. IL-10 positivity was seen in the dermal cell infiltrates and in T-cell lines in mycosis fungoides. The dermal IL-10 reaction in a skin biopsy from an active lesion in MF indicates the possibility for disease progression.

A case of a twelve-year-old girl with a big solid tumour in the right lung is presented. As malignancy could not be excluded, she was operated. A lobectomy was performed. Frozen section showed no malignancy. Histology showed inflammatory pseudotumour, which is a rare but important benign lung tumour in childhood. The recommended treatment is conservative resection.

An outbreak involving 20 cases of serogroup C meningococcal disease, predominantly among teenagers, occurred over a seven-month period in the Randers area of Denmark. The cases were caused by a serogroup C:2a:P1.2 sulphonamide-resistant strain. The available evidence was against the transmission being related to particular schools. The outbreak was experienced as three clusters. At two schools involved in the first and the third cluster of the outbreak, 351 students were examined regarding pharyngeal carriage of meningococci, 282 of whom were tested again 17 weeks later; 308 students attending two similar schools in a nearby area were examined once. The majority of strains isolated from group C carriers in the high-risk area were serologically indistinguishable from the outbreak strain (13/14 = 95%), but less often sulphonamide-resistant (5/13 = 38%). In both areas, the overall carrier rate (30%), the overall group C rate (3%) and, the carrier rate for the outbreak strain (1%) were the same. The attack rate for the outbreak strain differed significantly: 1/40 in the high-risk area versus 1/2.500 in the normal risk area. No conditions that might explain this difference were revealed. Immediately after recognition of the first and the third cluster, 780 and 13,300 students, respectively, were vaccinated with meningococcal polysaccharide vaccine A+C. It was concluded that the definition of target groups for vaccination should be liberal, because the "at risk" population may be difficult to recognize at the onset of an outbreak.

Late infantile neuronal lipofuscinosis was confirmed by electron microscopy in this case. At magnifications above 100,000 a particular alternating linear pattern of the curvilinear bodies was found.

Sera from 1) 8 AIDS patients with Pneumocystitis carinii pneumonia, 2) 13 HIV antibody-positive patients, 9 with AIDS and 4 with AIDS-related symptoms, all 13 without Pneumocystis carinii pneumonia, and 3) 36 healthy male blood donors, all HIV antibody negative, were examined for antibodies against Pneumocystis carinii using the indirect immunofluorescence antibody technique. Seven (87%) out of eight sera from group 1, 12 (92%) out of 13 sera from group 2, and 35 (97%) out of 36 sera from group 3 were positive. There was no significant difference between group 1 and 2, and group 2 and 3. The difference between group 1 and group 3 was significant (p = 0.03).

A kidney biopsy specimen with pronounced hemosiderosis from a patient with beta-thalassemia major was studied by light and electron microscopy, including X-ray microanalysis. Ferritin was absorbed from the glomerular ultrafiltrate through the parietal epithelial cells and the tubular epithelial cells and from the blood through the endothelial cells. It was transported in siderosomes into the surrounding basal lamina, where electron-dense deposits of hemosiderin were found in the outer part of the lamina densa and the reticular lamina. Fibrosis was seen as a reaction to the iron followed by severe atrophy of affected structures.

An outbreak involving 20 cases of serogroup C meningococcal disease, predominantly among teenagers, occurred over a 7-month period in the Randers area of Denmark. The cases were caused by serogroup C:2a:P1.2 sulphonamide-resistant strains. The available evidence was against the transmission being related to particular schools. The outbreak was experienced as 3 clusters. At 2 schools involved in the first and the third cluster of the outbreak, 351 students were examined regarding pharyngeal carriage of meningococci, 282 of whom were tested again 17 weeks later; 308 students attending two similar schools in a nearby area were examined once. The majority of strains isolated from group C carriers in the high-risk area were serologically indistinguishable from the outbreak strain (13/14 = 95%), but less often sulphonamide-resistant (5/13 = 38%). In both areas, the overall rate (30%), the overall group C rate (3%), the carrier rate for the outbreak strain (1%) were the same. The attack rate for the outbreak strain differed significantly: 1/40 in the high-risk area versus 1/2,500 in the normal risk area. No conditions that might explain this difference were revealed. Immediately after recognition of the first and the third cluster, 780 and 13,300 students, respectively, were vaccinated with meningococcal polysaccharide vaccine A+C. It was concluded that the definition of target groups for vaccination should be liberal, because the "at risk" population may be difficult to recognize at the onset of an outbreak.

A 38-year-old Omani woman, seven months pregnant, developed extensive zygomycosis involving maxillary and temporal bones. No evidence of any underlying immune deficiency was detected except that which may be attributed to pregnancy. After delivery the patient was treated with repeated courses of amphotericin B, which resulted in a complete clinical resolution. Zygomycosis in uncomplicated pregnancy has not been previously described.