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Objectives: Patients with suspected COVID-19 remain at risk for clinical deterioration after discharge and may benefit from home oxygen saturation (SpO 2 ) monitoring using portable pulse oximeter devices. Our study aims to evaluate patient engagement and compliance with a home SpO 2 monitoring program., Methods: This is a single center, prospective pilot study of patients being discharged from the ED or urgent care after evaluation of symptoms consistent with COVID-19. Subjects were given a portable pulse oximeter and instructed to obtain measurements at rest and with exertion twice daily for 14 days. Patients were contacted daily to collect recorded data. If attempts to contact the patient were unsuccessful for 3 consecutive days, patients were considered lost to follow up. The primary outcome of interest was patient engagement in the program which was defined as the percentage of patients that completed the 14-day study period, meaning they were not lost to follow up. Secondary outcomes included compliance with performing the SpO 2 readings. Patient compliance was calculated as a percentage of completed readings out of the total expected readings., Results: Fifty patients were enrolled - 2 withdrew and 1 was a screen failure. Overall, engagement in the program was 46.8% with no significant difference between those who tested positive for SARS-CoV-2 versus those who tested negative (48.2% vs 45%, p = 0.831). Median compliance overall was 42.9% (IQR 22.22-78.57). Median compliance for the positive group was 50.0% (IQR 20-85.71) and 42.86% (IQR 22.92-76.44) for the negative group (p= 0.838)., Conclusion: Our study demonstrated that there was acceptable engagement and compliance in a 14-day home SpO 2 monitoring program. These results support the use of home pulse oximetry monitoring in a select group of mildly ill patients with suspected COVID-19., Competing Interests: None declared, (© 2023 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved.)

Purpose: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood., Methods: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed., Results: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID., Conclusion: We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.

Lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and can be loaded by hybridization with fluorophore-DNA conjugates or with the anti-glaucoma drug travoprost by hybridizing an aptamer that binds the medication. In the travoprost-loaded NPs (Trav-NPs), the drug is bound by specific, non-covalent interactions, not requiring any chemical modification of the active pharmaceutical ingredient. Fluorescently labeled Trav-NPs show a long-lasting adherence to the eye, up to sixty minutes after eye drop instillation. Biosafety of the Trav-NPs was proved and in vivo. Ex vivo and in vivo quantification of travoprost via LC-MS revealed that Trav-NPs deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug. The data successfully show the applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of a major retinal eye disease, i.e. glaucoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND)., Methods: Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex., Results: Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners., Conclusions: A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.

Purpose: Most classical aniridia is caused by PAX6 haploinsufficiency. PAX6 missense variants can be hypomorphic or mimic haploinsufficiency. We hypothesized that missense variants also cause previously undescribed disease by altering the affinity and/or specificity of PAX6 genomic interactions., Methods: We screened PAX6 in 372 individuals with bilateral microphthalmia, anophthalmia, or coloboma (MAC) from the Medical Research Council Human Genetics Unit eye malformation cohort (HGU eye ) and reviewed data from the Deciphering Developmental Disorders study. We performed cluster analysis on PAX6-associated ocular phenotypes by variant type and molecular modeling of the structural impact of 86 different PAX6 causative missense variants., Results: Eight different PAX6 missense variants were identified in 17 individuals (15 families) with MAC, accounting for 4% (15/372) of our cohort. Seven altered the paired domain (p.[Arg26Gln]x1, p.[Gly36Val]x1, p.[Arg38Trp]x2, p.[Arg38Gln]x1, p.[Gly51Arg]x2, p.[Ser54Arg]x2, p.[Asn124Lys]x5) and one the homeodomain (p.[Asn260Tyr]x1). p.Ser54Arg and p.Asn124Lys were exclusively associated with severe bilateral microphthalmia. MAC-associated variants were predicted to alter but not ablate DNA interaction, consistent with the electrophoretic mobility shifts observed using mutant paired domains with well-characterized PAX6-binding sites. We found no strong evidence for novel PAX6-associated extraocular disease., Conclusion: Altering the affinity and specificity of PAX6-binding genome-wide provides a plausible mechanism for the worse-than-null effects of MAC-associated missense variants.

Purpose: To develop a comprehensive next-generation sequencing panel assay that screens genes known to cause developmental eye disorders and inherited eye disease and to evaluate its diagnostic yield in a pediatric cohort with malformations of the globe, anterior segment anomalies, childhood glaucoma, or a combination thereof., Design: Evaluation of diagnostic test., Participants: Two hundred seventy-seven children, 0 to 16 years of age, diagnosed with nonsyndromic or syndromic developmental eye defects without a genetic diagnosis., Methods: We developed a new oculome panel using a custom-designed Agilent SureSelect QXT target capture method (Agilent Technologies, Santa Clara, CA) to capture and perform parallel high-throughput sequencing analysis of 429 genes associated with eye disorders. Bidirectional Sanger sequencing confirmed suspected pathogenic variants., Main Outcome Measures: Collated clinical details and oculome molecular genetic results., Results: The oculome design covers 429 known eye disease genes; these are subdivided into 5 overlapping virtual subpanels for anterior segment developmental anomalies including glaucoma (ASDA; 59 genes), microphthalmia-anophthalmia-coloboma (MAC; 86 genes), congenital cataracts and lens-associated conditions (70 genes), retinal dystrophies (RET; 235 genes), and albinism (15 genes), as well as additional genes implicated in optic atrophy and complex strabismus (10 genes). Panel development and testing included analyzing 277 clinical samples and 3 positive control samples using Illumina sequencing platforms; more than 30× read depth was achieved for 99.5% of the targeted 1.77-Mb region. Bioinformatics analysis performed using a pipeline based on Freebayes and ExomeDepth to identify coding sequence and copy number variants, respectively, resulted in a definitive diagnosis in 68 of 277 samples, with variability in diagnostic yield between phenotypic subgroups: MAC, 8.2% (8 of 98 cases solved); ASDA, 24.8% (28 of 113 cases solved); other or syndromic, 37.5% (3 of 8 cases solved); RET, 42.8% (21 of 49 cases solved); and congenital cataracts and lens-associated conditions, 88.9% (8 of 9 cases solved)., Conclusions: The oculome test diagnoses a comprehensive range of genetic conditions affecting the development of the eye, potentially replacing protracted and costly multidisciplinary assessments and allowing for faster targeted management. The oculome enabled molecular diagnosis of a significant number of cases in our sample cohort of varied ocular birth defects., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in outpatient shoulder arthroplasty (SA); however, the clinical evidence behind this practice is sparse. The purpose of this study was to assess the safety of outpatient SA performed in an ambulatory surgery center and to determine patient factors that are associated with increased risk for perioperative complications or dissatisfaction., Methods: Patient demographics and operative variables were collected retrospectively for patients undergoing outpatient SA at 2 ambulatory surgery centers with a minimum follow-up of 90 days. Patients completed a postsurgery questionnaire about their experience, satisfaction, pain control, and health care use., Results: Forty-one anatomic total SAs (n = 32) and reverse SAs (n = 9) with a mean follow-up of 60 weeks (16.4 weeks-3 years) were included. The mean age, body mass index, Charlson Comorbidity Index, and American Society of Anesthesiologists class were 60.6 ± 4.8 years, 31.8 ± 6.6, 2.9 ± 1.9, and 2.3 ± 0.6, respectively. Three (7.3%) minor complications occurred within 90 days of the SA, none before first follow-up. Two patients stayed in the ambulatory surgery center 23-hour observation unit. Thirty-five patients (85.4%) completed the questionnaire, of whom 97.0% (n = 32) were satisfied with the outpatient procedure. Two patients had difficulties with postoperative pain control and were taking chronic narcotic medication before surgery., Conclusion: Outpatient SA in an ambulatory surgery center is safe with high patient satisfaction and low rates of perioperative complications. Although larger cohorts are required to adequately determine which patients will be appropriate candidates for an outpatient SA, our findings do suggest that patients with a history of preoperative narcotic use may have difficulties or dissatisfaction with outpatient SA.

abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways-from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as complementarity-determining regions and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing "unusual residues" (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species. abYsis is useful for any researcher specializing in antibody engineering, especially those developing antibodies as drugs. abYsis is available at www.abysis.org., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: To report on patterns of optometry prescribing and adherence to prescribing regulations at a tertiary care ophthalmology centre., Design: Prospective cohort study., Participants: All new referrals from optometrists and other health care professionals to the emergency eye care service (n = 1965) between July 2011 and June 2012, as well as optometry referrals to 2 subspecialty services (glaucoma [n = 71] and cornea [n = 212])., Methods: In our primary analysis, the frequency of prescribing and classes of medications prescribed were reported and compared amongst various referral sources to the emergency eye care service. As a secondary analysis, we reported frequency of prescribing in optometry referrals to 2 subspecialty clinics. Adherence to prescribing guidelines was reported for all optometry referrals., Results: Of 296 referrals from optometrists to the emergency eye care service, 20 (6.8%) had received a prescription medication; this was significantly less compared to emergency and family physicians (p < 0.001). Topical antibiotics were the most frequently prescribed medication class. The frequency of prescribing by optometrists was 5.2% (11/212) and 4.2% (3/71) for patients referred to the cornea and glaucoma services, respectively. Among those patients referred after being given a prescription for a glaucoma medication by an optometrist, 89% cases (8/9) did not adhere to prescribing regulations., Conclusions: After the introduction of prescribing privileges, optometrists prescribe a variety of medications in their practices. Current prescribing guidelines are not always followed in practice, suggesting that continued study and collaboration is necessary to create an optimal model of interdisciplinary care that provides access to the highest quality of care., (Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To quantify the association between subjective visual reduction (SVR) and retinal pathology in patients with acute-onset monocular floaters or flashes, or both., Design, Setting, and Participants: Prospective cohorts study involving all new patients referred for acute-onset floaters or flashes, or both, to a tertiary care emergency eye clinic in Kingston, Ontario, between July 1, 2011, and June 29, 2012 (n = 333)., Methods: All patients were evaluated for the presence of SVR in a standardized fashion, as well as other known risk factors for retina pathology including a family history of retinal tear or retinal detachment, a personal history of retinal tear or detachment, high myopia, and ocular trauma. Our major outcome was urgent retinal pathology, defined as retina pathology requiring a same-day referral to a retina specialist for evaluation, management, or both., Results: SVR was strongly associated with retinal pathology (likelihood ratio 7.9, 95% CI 5.2-12.1)., Conclusions: Patients with SVR are at increased risk for urgent retinal pathology and should be triaged for urgent ophthalmologic examination., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To report the causative factors and surgical candidacy of patients referred to an oculoplastic surgery clinic for the complaint of epiphora., Design: Prospective observational study., Participants: Consecutive patients (n = 159) referred to a tertiary care oculoplastic surgery clinic over a 12-month period for the complaint of epiphora., Methods: The causative factor most responsible for tearing was determined based on clinical examination by the principal investigator, who was blinded to referral source. Patients were considered surgical candidates with a diagnosis of significant nasolacrimal duct obstruction, lid malposition, or pump dysfunction. The primary outcome was the percentage of referrals that were surgical candidates, classified by referral source., Results: The most common cause of tearing was nasolacrimal duct obstruction, occurring in 53 of 159 (33%) patients. The percentage of surgical candidates was highest in referrals from ophthalmologists (82%), followed by optometrists (67%) and family physicians (55%; p = 0.011 for difference between ophthalmologists and family physicians)., Conclusions: Epiphora may be because of a variety of causes, some of which are amendable to surgical treatment. In the absence of an obvious cause, a trial of lubrication by the family physician is warranted before referral being made to an oculoplastic surgeon., (Copyright © 2014. Published by Elsevier Inc.)

Objective: The purpose of this study is to determine whether patients with acute posterior vitreous detachment (PVD) who develop delayed retinal tears within the first 6 weeks after initial presentation have predictive characteristics., Design: Prospective cohort study., Participants: All patients presenting to the Hotel Dieu Hospital Emergency Eye Clinic between September 2008 and July 2009 diagnosed with acute PVD were offered enrollment., Methods: At the initial visit, patients were given the previously validated Queen's University Posterior Vitreous Detachment Patient Diary to record their daily symptoms for 6 weeks. Two or 6 weeks later, patients were reexamined in detail, and their diaries were collected and analyzed. Exact logistic regression was used to establish characteristics predictive of delayed retinal tears., Results: In our study population of 99 patients, 2 developed delayed retinal tears. One had retinal hemorrhages and the other had a cloud-like floater at initial presentation. Vitreal or retinal hemorrhage, large number of floaters at initial presentation, and high floater frequency at initial presentation indicated a high risk of delayed retinal tear formation, yielding a median unbiased estimated odds ratio of 36.18 with p value 0.009. No other presenting risk factors or symptomatology followed daily over the first 6 weeks after acute PVD were predictive of delayed retinal tear formation., Conclusions: PVD patients with retinal or vitreal hemorrhage, a significant number of floaters or a cloud like appearance to the floaters, or high floater frequency are at higher risk of developing delayed retinal tears., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: While current emphases on operative teaching focus on "virtual" education, residents and faculty engage most intimately in the operating room. The utilization of intraoperative teaching techniques, drawn from adult education principles, is understudied., Design: A survey with both quantitative and qualitative elements was administered to surgical residents and their faculty. Thirty-eight analogous questions regarding teaching techniques, populating four general domains, were rated for frequency of application. Respondents were asked to rank best teaching practices and identify other effective educational approaches using open-ended questions., Setting: University-based general surgical residency (5 institutions)., Participants: General surgical residents and their faculty., Results: 46 residents (77%) and 37 faculty (63%; mean 17 yrs experience) completed the survey. There was significant disagreement between residents and faculty in how frequently 32 of the 38 teaching techniques were applied (all p < 0.032). Faculty rated the technique "I set and communicate high standards" as the most frequently applied strategy, while residents rated "The faculty demonstrate technical consistency" the highest. The least employed approach, acknowledged by both groups, was "The faculty ask how they might improve their teaching." There were few differences between perceptions and preferences of junior vs. senior learners, and junior vs. senior faculty. Resident and faculty appreciation of most-effective teaching approaches was similar. Qualitative analysis of the open-ended questions yielded themes which resonate with both learners and teachers: communication processes, time pressures, optimization of the work/teaching environment, teacher engagement, patience/tolerance, autonomy, feedback, learner preparedness, and patient advocacy., Conclusions: The perceptions of residents and faculty regarding the frequency of using effective approaches for operative teaching are disparate. While faculty appear to value adult learning principles and perceive that they are employed regularly, residents have a discrepant viewpoint. However, themes that were identified by both residents and faculty through qualitative analysis provide the foundation for educational process improvements., (Copyright © 2011 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the visual function of patients with posterior vitreous detachment (PVD)changes between the initial visit and a 6-week follow-up visit, and to compare their visual function with that of patients with macular degeneration, cataract, glaucoma, low vision, cytomegalovirus (CMV) retinitis, or diabetic retinopathy and a reference population., Design: Prospective cohort study., Participants: All patients presenting to the Hotel Dieu Hospital Emergency Eye Clinic between September 2008 and June 2009 who were diagnosed with acute PVD were offered enrollment in the study., Methods: Patients were administered the National Eye Institute Visual Function Questionnaire NEI VFQ-25 at two points in time. The composite scores from the initial and the 6-week visits were compared. The scores were also compared with established normative data and 6 ophthalmologic diagnoses., Results: The NEI VFQ-25 composite score for patients with acute PVD (n = 84) at baseline was 93.26 ± 5.59 (mean ± SD). After 6 weeks and a second ocular examination, there was no statistical difference in the composite score of 93.47 ± 6.20 (mean ± SD). (1-sided paired t-test, t = 0.57; P = 0.28)., Conclusions: The visual function of patients with acute PVD remains stable over the first 6 weeks after diagnosis. It is significantly higher than that of patients with 6 other ophthalmologic conditions but comparable to that of a normal population., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or venous thromboses, pregnancy loss and the presence of antiphospholipid antibodies (aPL). One of the discussed mechanisms of this thrombotic activity in APS patients is attributed to TNFalpha secretion in monocytes after aPL stimulation. To investigate this mechanism in detail, we employed a monoclonal aPL and IgG fractions of APS patients for stimulation of human peripheral monocytes. Stimulation with this monoclonal aPL resulted in an increased expression and secretion of TNFalpha, caused by specific upregulation of TLR8 mRNA and protein expression levels. To confirm the specificity of this finding we could demonstrate that the TNFalpha enhancement could be neutralized by a TLR8-specific inhibitory DNA-oligonucleotide and could be further increased by adding the specific ligands for TLR8. Using APS patients IgG fractions for stimulation of peripheral monocytes revealed a similar TLR8 mRNA elevation and increase in TNFalpha-production. Furthermore the TLR8 expression level in PBMC's of APS patients was as well significantly elevated. It could be demonstrated that the TNFalpha release in monocytes resulting from aPL stimulation was exclusively induced by TLR8 engagement. This could be confirmed in PBMC's of APS patients, hinting that endogenous stimulation of TLR8 in APS patients and consecutive elevation of TNFalpha promotes a proinflammatory environment., (2009 Elsevier GmbH. All rights reserved.)

TLRs represent the first line of defense against invading pathogens in the innate immune system. Certain cytokines are important mediators and essentially necessary to assure an appropriately regulated immune response. Recent data gave initial evidence that IL-1beta is one of the most relevant members of these regulating cytokines. We investigated the induction of IL-1beta production in monocytes and pDCs stimulated with ligands for TLR7 and TLR8 and with antiphospholipid antibodies (aPL). Using human monocytes and pDCs for stimulation with specific TLR7 and TLR8 ligands such as resiquimod (R848) and single stranded RNA (RNA42) as well as with a human monoclonal aPL HL5B resulted in a specific upregulation of IL-1beta mRNA and protein in these cells. Determination of expression-levels using real-time RT-PCR showed significantly augmented TLR-dependent IL-1beta and caspase-1 expression. This increase could be substantially enhanced by adding the monoclonal aPL HL5B. To demonstrate the direct dependency between TLR stimulation and IL-1beta production, specific TLR inhibitors were applied and the IL-1beta and caspase-1 secretion could be explicitly decreased. The respective protein levels were determined using Western Blot, FACS analysis or ELISA assays. In conclusion we demonstrated that the downstream signaling pathway of TLR7 and TLR8 in monocytes and pDCs after stimulation with specific ligands included not only the secretion of cytokines such as TNFalpha and IL-1beta but as well the activation of necessary regulating proteins like caspase-1. APL seem to enforce this process hinting that endogenous stimulation of TLRs in the Antiphospholipid Syndrome (APS) patients resulted in enhanced secretion of proinflammatory cytokines.

The understanding of autoimmune diseases experienced an impressive boost since the Toll-like receptors (TLRs) have been identified as possible key players in autoimmune pathophysiology. Although these receptors recognize a variety of structures derived from viruses, bacteria and fungi leading to subsequent initiation of the relevant immune responses recent data support the idea that TLRs are crucial in the induction and perpetuation of certain autoimmune diseases, especially the systemic lupus erythematosus (SLE). In this review we will summarize recent data on involvement of TLRs in the development of autoimmune diseases. This review will focus on TLRs 7, 8 and 9 which were originally identified as receptors specific for bacterial and viral RNA/DNA, but more recent in vitro and in vivo studies have linked these receptors to the detection of host RNA, DNA, and RNA- or DNA-associated proteins in the context of autoimmunity.

There must be no pretense in medicine. When a physician orders an electrocardiogram on a patient he or she must be able to interpret it. Not only that, he or she must understand the mechanism responsible for the abnormality and how the abnormality fits, or does not fit, with the other data collected from the patient.

A bathochromic shift for both Soret and Q bands in the polyCo(III)PP were indicative of Co(III) oxidation state in film. The presence of an isosbestic point indicates a chemical equilibrium between polyCo(III)PP (band I) in polyCo(III)PP with water as axial neutral ligand (band II). Concentration levels of iodide of 10(-1) M showed irreversible broadening of Soret band with a maximum shift from 400 nm to 380 nm attributed to film reduction. The thiocyanate anion shows a remarkable effect on polyCo(III)PP spectra. The degree of configuration interaction for Q and B transitions is nearly constant in air and water for Ni(II)PP, Cu(II)PP and Zn(II)PP films. The poly[Co(III)-protoporphyrin IX] showed strong deviation from the pattern. This result indicates that the Co atom does not present a planar conformation in polyCo(III)PP which is consistent with the less packed structure of this film. The apparent diffusion coefficients (D') were calculated for electroactive species using the polyNi(II)PP chemically modified electrode, with an experiment short enough to avoid preconcentration. D' was compared with D (diffusion coefficient), obtained with the bare working electrode. Apparent diffusion coefficients (D') changed regularly with molecular volume indicating certain molecular sieving effect.

Background: Patients with large (> or = 5.0 cm) abdominal aortic aneurysms (AAA) frequently have marked associated coronary artery disease. We hypothesized that a single operation for coronary artery bypass grafting (CABG)/AAA would provide equivalent, if not improved, patient care while decreasing postoperative length of stay and hospital costs compared with staged procedures., Methods: Eleven patients to date have undergone a combined procedure at our institution. Ten underwent CABG followed by AAA repair, whereas one patient received an aortic valve replacement before aneurysm repair. We performed a retrospective analysis comparing the postoperative length of stay and hospital costs for this single procedure to a combined cohort of 20 randomly selected patients who either received AAA repair (n = 10) or standard CABG (n = 10) during the same time period., Results: No operative mortality has been reported. There were no episodes of neurologic deficit or cardiac complication after these procedures. The postoperative length of stay was significantly decreased for the CABG/AAA group compared with the combined postoperative length of stay for the AAA plus CABG group (7.44+/-0.88 days versus 14.10+/-2.00; p = 0.012). Total hospital costs were also significantly decreased for the CABG/AAA group compared with total hospital costs for the AAA plus CABG group ($22,941+/-$1,933 versus $34,076+/-$2,534; p = 0.003)., Conclusions: A single operation for coronary revascularization and AAA repair is safe and effective. Simultaneous CABG and AAA repair substantially decreases postoperative length of stay and hospital costs while avoiding possible interim aneurysm rupture and repeat anesthesia.

Purpose: This study was done to evaluate the diagnostic utility of dynamic positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) imaging in patients with suspected malignant pulmonary lesions. We wanted to test the hypothesis that the rate of FDG uptake (FDG influx constant values) would differentiate malignant from benign lung or mediastinal lesions., Materials and Methods: We performed segmental dynamic PET imaging studies following administration of FDG in 19 patients with indeterminate pulmonary lesions based on chest radiograph and/or CT scans. Patlak analysis was done to compute Ki (FDG influx constant) values and compared with FDG standardized uptake values (SUVs) and histology., Results: FDG Ki values (mean+/-SD) were significantly greater (p < 0.01) in all 12 malignant lesions (0.029+/-0.02) as compared with 7 benign lesions (0.0024+/-0.0011) with good correlation to the SUV values. Distinct time activity curve patterns were identified in malignant and benign lesions with continued uptake in malignant lesions., Conclusion: Dynamic PET-FDG imaging accurately differentiates malignant from benign pulmonary lesions. In certain cases with equivocal findings on visual analysis and SUV values, dynamic imaging may be further helpful in differentiating benign and malignant lesions.

A quantitative model is derived for tannin-protein binding and protein precipitation in solution. This model is based on the assumption that precipitation occurs when the number of tannin molecules associated with one protein molecule attains a critical value. Precipitation occurs at this point because tannin crosslinking causes formation of large protein aggregates. Analytical expressions were derived for the dependence of protein precipitate yields upon the concentrations of the protein and tannin in solution. This expression fits reasonably well the experimentally observed bell-shaped dependencies of bovine serum albumin or gelatin precipitation upon total protein and tannin concentrations., (Copyright 1998 Academic Press.)

The use of Tamoxifen as treatment for breast cancer is well established and its use experimentally as prophylaxis is promising, but little has been written about mammographically detected changes in breast parenchyma as a result of Tamoxifen therapy. We report two cases of spontaneous regression of breast cysts after Tamoxifen therapy for premenopausal breast cancer in the contralateral breast.

We present a case illustrating the complementary role of CT and angiography in evaluation of a slowly expanding vascular thoracic mass representing aneurysmal enlargement in an aberrant right subclavian artery. Anatomy, embryology, incidence, and imaging of aberrant right subclavian artery, bicarotid trunk, and aneurysmal dilatation of the diverticulum of Kommerell are reviewed.

Cellular inactivation of Escherichia coli by the neutrophil-generated toxin, hypochlorous acid, is accompanied by inactivation of its plasma membrane-localized F1-ATPase. The nature of oxidative damage leading to inactivation of this enzyme was probed by SDS-PAGE and 2D-gel electrophoresis and by hybrid reconstitution studies using purified subunits from untreated and extensively oxidized bacteria. The data indicate that inactivation is due to selective oxidation of a few highly vulnerable sites; although damage occurred to each of the alpha, beta, and gamma-subunits required for soluble ATP hydrolase activity, the extent of damage was insufficient to alter their electrophoretic properties.

Management of patients after operative repair of abdominal aortic aneurysms can be further complicated if primary closure of the abdominal wall cannot be technically accomplished or is associated with profound increases in intraabdominal and peak inspiratory pressures. We recently treated five patients with ruptured abdominal aortic aneurysms and one patient with a ruptured thoracoabdominal aneurysm whose abdominal incisions had to be closed with a Dacron reinforced, silicone sheet. All patients were hemodynamically unstable either at admission to the hospital or became so during operation. Four patients required the insertion of a silicone rubber sheet at the primary operation because of massive retroperitoneal hematoma or edema of the bowel wall or both. Incisions in two patients were closed primarily, but the patients required reexploration and secondary closure with silicone rubber sheets because of the development of marked increases in peak inspiratory pressures, intraabdominal pressures, and decreased urinary output. Four of the six patients subsequently underwent successful removal of the silicone rubber sheets with delayed primary closure of the abdominal wall, and two others died before removal. The patient with the ruptured thoracoabdominal aneurysm died on postoperative day 20 because of pulmonary sepsis but had a healed abdominal incision. The three surviving patients have been discharged. A silicone rubber sheet may be necessary for closure of the abdominal wall after repair of ruptured abdominal aortic aneurysm in patients where primary abdominal wall closure is impossible or where it results in compromise in respiratory or renal function.

Radioactivity from 3H-[methyl]-S-adenosyl-L-methionine (AdoMet) was covalently bound to protein-O-carboxylmethyltransferase and phenylethanolamine N-methyltransferase following 10-15 min irradiation by short-wave ultraviolet light. This photoaffinity binding of 3H-[methyl]-AdoMet was blocked by S-adenosylhomocysteine and sinefungin, but was not affected by 5 mM dithiothreitol. The binding was also inhibited by including methyl acceptors such as calmodulin (protein-O-carboxylmethyltransferase) or phenylethanolamine (phenylethanolamine N-methyltransferase) in the photoaffinity incubation. Staphlococcus V8 protease digests of 3H-[methyl]-AdoMet/enzyme complexes revealed that the primary structure around the AdoMet binding site is different in these two enzymes. Thus, protein-O-carboxylmethyltransferase, a large molecule methyltransferase, can covalently bind 3H-[methyl]-AdoMet in a manner similar to that of phenylethanolamine-N-methyltransferase.

CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl)piperidine] HCl, a known serotonin inhibitor, also inhibits rat brainstem monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in both in vivo and in vitro experiments. Serotonin (5-HT) deamination by MAO-A is inhibited 35% at a dose of 100 mg/kg i.p. in vivo. Similar experiments show a maximal 20% decrease in phenylethylamine (PEA) deamination by MAO-B at a dosage of 30 mg/kg i.p. Over the range of 0.1 to 10 mg/kg i.p., CGP 6085 A decreases 5-HIAA levels in the brainstem. This in vivo inhibition of MAO activity is confirmed by in vitro experiments. In vitro studies in rat brainstem mitochondrial preparations show a dose-dependent, reversible, inhibition of MAO using tyramine as the substrate for the enzyme reaction. With an in vitro IC50 of 2-3 microM, the potency of CGP 6085 A is comparable to pargyline.

We retrospectively analyzed the clinical data on 3479 consecutive patients having coronary bypass surgery. Patients with triple vessel and left main coronary disease had a greater frequency of inotropic requirements than did patients with single or double vessel disease (7.9% and 8.6% versus 3.8% and 4.2%; P less than 0.001). Presence of previous myocardial infarction, heart failure, or left ventricular contraction abnormalities significantly decreased the ability to achieve complete revascularization with bypass grafting. Hospital mortality since 1976 has been 0.8% (25/3040). Hospital mortality was significantly increased by history of myocardial infarction (P less than 0.001), hypertension (P less than 0.05), heart failure (P less than 0.01), extent of anatomic disease (P less than 0.005), presence of preoperative ST-T wave changes (P less than 0.001), and severe abnormalities of left ventricular function (P less than 0.001). Anginal pattern, history of hypertension, previous myocardial infarction, preoperative heart failure but not perioperative myocardial infarction significantly affected long-term survival. Patients with normal left ventricular function had excellent 42-month survival regardless of vessel disease. Inability to achieve complete revascularization did not adversely affect hospital mortality, but did significantly reduce late survival. Although bypass grafting improves survival in patients with multivessel disease and left ventricular dysfunction, the benefits appear to be significantly reduced when left ventricular damage has occurred.

CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl], a reported serotonin uptake and MAO (16) inhibitor, is a potent hypothermic agent. The hypothermic action of CGP 6085 A is dose dependent with a maximal reduction in rectal core temperature of greater than 1 degree C within one hour after drug administration. Fluoxetine and citalopram elicit a similar response at equal doses. These results suggest that inhibition of serotonin uptake may produce the hypothermic effect. To assess the in vivo action of CGP 6085 A in inhibiting hypothalamic serotonin uptake, CGP 6085 A (10 mg/kg) was injected one hour prior to injection of 3-hydroxy-4-methyl-alpha-ethyl-phenylethylamine (H75/12), a serotonin depletor. The ability of CGP 6085 A to block the uptake of H75/12 by the 5HT uptake system was indicative of its ability to block serotonin uptake. Pretreatment with p-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, resulted in the loss of the hypothermic response to CGP 6085 A. Thus, these data are consistent with the idea that CGP 6085 A may produce its hypothermic response by inhibiting serotonin uptake.

Standard procedures for the purification of phenylethanolamine N-methyltransferase were modified by the addition of an affinity chromatography step utilizing immobilized S-adenosyl-L-homocysteine and by use of preparative isoelectric focusing. Enzyme derived from bovine adrenal medullae was bound to S-adenosyl-L-homocysteine agarose, and could be eluted with 0.1 M NaCl. Concentrations of S-adenosyl-L-methionine as high as 10 mM were ineffective in eluting the enzyme. Preparative isoelectric focusing of bovine phenylethanolamine N-methyltransferase showed a single peak with the pI = 4.95. The potential use of immobilized S-adenosyl-L-homocysteine in the differential separation of phenylethanolamine N-methyltransferase from other methyltransferase enzymes is discussed.

The stimulation by ADP or arachidonic acid of the aggregation of human platelets in plasma was inhibited by 4-hydroxynonenal (HNE). This reduction of aggregation was time related, and was increased by prolonged preincubation of the platelets with the aldehyde. HNE was more potent than its homologue 4-hydroxypentenal (HPE). HNE was less active in decreasing the aggregation induced by calcium ionophore A23187 or collagen in comparison with ADP. HNE was inactive against aggregation of platelet-rich plasma (PRP) stimulated by thrombin whereas it potently inhibited the aggregation of washed platelets in response to both thrombin and collagen. Platelets were found to degrade HNE, and mechanisms additional to covalent binding to glutathione are indicated by the results obtained. The aldehydes, including HNE, generated by platelets originated principally from arachidonic acid metabolism.