Patient Perception of Cough in Interstitial Lung Disease; Impact of Cough Hypersensitivity.

INTRODUCTION: Cough is common in interstitial lung disease (ILD) and is associated with disease progression, yet its mechanisms are understudied. We investigated cough hypersensitivity features and impact in ILD. METHODS: Participants with ILD and cough (n = 195) completed a multiple choice and free text questionnaire on cough sensations/triggers and impacts. RESULTS: The majority of participants were male (54%), aged > 65 (64%), with idiopathic pulmonary fibrosis (IPF, 75%). Common cough triggers were body position (74%), physical activity (72%), and talking (62%). Common laryngeal sensations were globus (43%), and itch/tickle (42%). Cough impacted everyday life in 55%, and all activities in 31%, causing exhaustion (59%), social embarrassment (70%), urinary incontinence (46% females), and syncope/pre-syncope (12%). The total number of cough-provoking sensations/triggers correlated with impacts; ρ = 0.73, p < 0.001. CONCLUSION: Cough hypersensitivity symptoms are prevalent in ILD and detrimentally affect quality of life. Further studies investigating mechanisms of cough hypersensitivity and targeted pharmacotherapy are warranted.

Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up.

OBJECTIVES: Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non-small-cell lung cancer (NSCLC). METHODS: Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs-landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)-were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. RESULTS: For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). CONCLUSIONS: We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. HIGHLIGHTS: Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up.Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes.Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data.Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting.Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup.

Migrant status and risk of compulsory admission at first diagnosis of psychotic disorder: a population-based cohort study in Sweden.

BACKGROUND: Minority ethnic and migrant groups face an elevated risk of compulsory admission for mental illness. There are overlapping cultural, socio-demographic, and structural explanations for this risk that require further investigation. METHODS: By linking Swedish national register data, we established a cohort of persons first diagnosed with a psychotic disorder between 2001 and 2016. We used multilevel mixed-effects logistic modelling to investigate variation in compulsory admission at first diagnosis of psychosis across migrant and Swedish-born groups with individual and neighbourhood-level covariates. RESULTS: Our cohort included 12 000 individuals, with 1298 (10.8%) admitted compulsorily. In an unadjusted model, being a migrant [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.26-1.73] or child of a migrant (OR 1.27; 95% CI 1.10-1.47) increased risk of compulsory admission. However after multivariable modelling, region-of-origin provided a better fit to the data than migrant status; excess risk of compulsory admission was elevated for individuals from sub-Saharan African (OR 1.94; 95% CI 1.51-2.49), Middle Eastern and North African (OR 1.46; 95% CI 1.17-1.81), non-Nordic European (OR 1.27; 95% CI 1.01-1.61), and mixed Swedish-Nordic backgrounds (OR 1.33; 95% CI 1.03-1.72). Risk of compulsory admission was greater in more densely populated neighbourhoods [OR per standard deviation (s.d.) increase in the exposure: 1.12, 95% CI 1.06-1.18], an effect that appeared to be driven by own-region migrant density (OR per s.d. increase in exposure: 1.12; 95% CI 1.02-1.24). CONCLUSIONS: Inequalities in the risk of compulsory admission by migrant status, region-of-origin, urban living and own-region migrant density highlight discernible factors which raise barriers to equitable care and provide potential targets for intervention.

Dissolved organic nutrient uptake by riverine phytoplankton varies along a gradient of nutrient enrichment.

The concentration of dissolved organic matter (DOM) in freshwaters is increasing in large areas of the world. In addition to carbon, DOM contains nitrogen and phosphorus and there is growing concern that these organic nutrients may be bioavailable and contribute to eutrophication. However, relatively few studies have assessed the potential for dissolved organic nitrogen (DON) or dissolved organic phosphorus (DOP) compounds to be bioavailable to natural river phytoplankton communities at different locations or times. Temporal and spatial variations in uptake, relative to environmental characteristics were examined at six riverine sites in two contrasting catchments in the UK. This study also examined how the uptake by riverine phytoplankton of four DON and four DOP compounds commonly found in rivers, varied with concentration. Total nitrogen (TN) and phosphorus (TP) concentrations, the proportion of inorganic nutrient species, and nutrient limitation varied temporally and spatially, as did the potential for DON and DOP uptake. All eight of the DOM compounds tested were bioavailable, but to different extents. Organic nutrient use depended on the concentration of the organic compound supplied, with simple compounds (urea and glucose-6-phosphate) supporting algal growth even at very low concentrations. DON use was negatively correlated with the TN and ammonia concentration and DOP use was negatively correlated with soluble reactive phosphorus (SRP) and dissolved organic carbon (DOC) concentration. The evidence indicates that DOM in rivers has been overlooked as a potential source of nutrients to phytoplankton and therefore as an agent of eutrophication.

Identifying critical source areas using multiple methods for effective diffuse pollution mitigation.

Diffuse pollution from agriculture constitutes a key pressure on the water quality of freshwaters and is frequently the cause of ecological degradation. The problem of diffuse pollution can be conceptualised with a source-mobilisation-pathway (or delivery)-impact model, whereby the combination of high source risk and strong connected pathways leads to 'critical source areas' (CSAs). These areas are where most diffuse pollution will originate, and hence are the optimal places to implement mitigation measures. However, identifying the locations of these areas is a key problem across different spatial scales within catchments. A number of approaches are frequently used for this assessment, although comparisons of these assessments are rarely carried out. We evaluate the CSAs identified via traditional walkover surveys supported by three different approaches, highlighting their benefits and disadvantages. These include a custom designed smartphone app; a desktop geographic information system (GIS) and terrain analysis-based SCIMAP (Sensitive Catchment Integrated Modelling and Analysis Platform) approach; and the use of a high spatial resolution drone dataset as an improved input data for SCIMAP modelling. Each of these methods captures the locations of the CSAs, revealing similarities and differences in the prioritisation of CSA features. The differences are due to the temporal and spatial resolution of the three methods such as the use of static land cover information, the ability to capture small scale features, such as gateways and the incomplete catchment coverage of the walkover survey. The relative costs and output resolutions of the three methods indicate that they are suitable for application at different catchment scales in conjunction with other methods. Based on the results in this paper, it is recommended that a multi-evidence-based approach to diffuse pollution management is taken across catchment spatial scales, incorporating local knowledge from the walkover with the different data resolutions of the SCIMAP approach.

Phytoplankton community responses in a shallow lake following lanthanum-bentonite application.

The release of phosphorus (P) from bed sediments to the overlying water can delay the recovery of lakes for decades following reductions in catchment contributions, preventing water quality targets being met within timeframes set out by environmental legislation (e.g. EU Water Framework Directive: WFD). Therefore supplementary solutions for restoring lakes have been explored, including the capping of sediment P sources using a lanthanum (La)-modified bentonite clay to reduce internal P loading and enhance the recovery process. Here we present results from Loch Flemington where the first long-term field trial documenting responses of phytoplankton community structure and abundance, and the UK WFD phytoplankton metric to a La-bentonite application was performed. A Before-After-Control-Impact (BACI) analysis was used to distinguish natural variability from treatment effect and confirmed significant reductions in the magnitude of summer cyanobacterial blooms in Loch Flemington, relative to the control site, following La-bentonite application. However this initial cyanobacterial response was not sustained beyond two years after application, which implied that the reduction in internal P loading was short-lived; several possible explanations for this are discussed. One reason is that this ecological quality indicator is sensitive to inter-annual variability in weather patterns, particularly summer rainfall and water temperature. Over the monitoring period, the phytoplankton community structure of Loch Flemington became less dominated by cyanobacteria and more functionally diverse. This resulted in continual improvements in the phytoplankton compositional and abundance metrics, which were not observed at the control site, and may suggest an ecological response to the sustained reduction in filterable reactive phosphorus (FRP) concentration following La-bentonite application. Overall, phytoplankton classification indicated that the lake moved from poor to moderate ecological status but did not reach the proxy water quality target (i.e. WFD Good Ecological Status) within four years of the application. As for many other shallow lakes, the effective control of internal P loading in Loch Flemington will require further implementation of both in-lake and catchment-based measures. Our work emphasizes the need for appropriate experimental design and long-term monitoring programmes, to ascertain the efficacy of intervention measures in delivering environmental improvements at the field scale.

A cloud based tool for knowledge exchange on local scale flood risk.

There is an emerging and urgent need for new approaches for the management of environmental challenges such as flood hazard in the broad context of sustainability. This requires a new way of working which bridges disciplines and organisations, and that breaks down science-culture boundaries. With this, there is growing recognition that the appropriate involvement of local communities in catchment management decisions can result in multiple benefits. However, new tools are required to connect organisations and communities. The growth of cloud based technologies offers a novel way to facilitate this process of exchange of information in environmental science and management; however, stakeholders need to be engaged with as part of the development process from the beginning rather than being presented with a final product at the end. Here we present the development of a pilot Local Environmental Virtual Observatory Flooding Tool. The aim was to develop a cloud based learning platform for stakeholders, bringing together fragmented data, models and visualisation tools that will enable these stakeholders to make scientifically informed environmental management decisions at the local scale. It has been developed by engaging with different stakeholder groups in three catchment case studies in the UK and a panel of national experts in relevant topic areas. However, these case study catchments are typical of many northern latitude catchments. The tool was designed to communicate flood risk in locally impacted communities whilst engaging with landowners/farmers about the risk of runoff from the farmed landscape. It has been developed iteratively to reflect the needs, interests and capabilities of a wide range of stakeholders. The pilot tool combines cloud based services, local catchment datasets, a hydrological model and bespoke visualisation tools to explore real time hydrometric data and the impact of flood risk caused by future land use changes. The novel aspects of the pilot tool are; the co-evolution of tools on a cloud based platform with stakeholders, policy and scientists; encouraging different science disciplines to work together; a wealth of information that is accessible and understandable to a range of stakeholders; and provides a framework for how to approach the development of such a cloud based tool in the future. Above all, stakeholders saw the tool and the potential of cloud technologies as an effective means to taking a whole systems approach to solving environmental issues. This sense of community ownership is essential in order to facilitate future appropriate and acceptable land use management decisions to be co-developed by local catchment communities. The development processes and the resulting pilot tool could be applied to local catchments globally to facilitate bottom up catchment management approaches.

Episodic waveforms in the electroencephalogram during general anaesthesia: a study of patterns of response to noxious stimuli.

Previous studies of the electroencephalogram (EEG) during anaesthesia have identified two distinct patterns of change in response to a noxious stimulus, a classical arousal pattern and a paradoxical arousal pattern. We developed methods of EEG analysis to quantify episodic EEG patterns--namely sleep spindle-like ('10 Hz-score') and burst-suppression-like fluctuations in high frequencies ('high frequency variation index')--and used traditional power spectral quantification of non-episodic delta waves. We studied 30 healthy adult patients undergoing elective surgery under general anaesthesia with propofol, fentanyl (1.0, 2.5 or 4.0 microg/kg, n=10 for each group), muscle relaxant and sevoflurane. Prefrontal EEG data were recorded during the operation and analysed for changes in episodic patterns before and after noxious stimuli (intubation and incision). Before noxious stimuli, the EEG patterns varied markedly between patients and were not strongly correlated to calculated effect-site concentrations of fentanyl, propofol or sevoflurane. Noxious stimuli reduced the 10 Hz-score from 0.25 to 0.20 (P = 0.01) after intubation and from 0.33 to 0.27 (P = 0.01) after incision; and high frequency variation index from 2.8 to 2.0 (P=0.02) after incision--the classical arousal pattern. The nociception-induced reduction in spindles was greater in the low-dose fentanyl group (P = 0.01). There was less tachycardia in the high-dose fentanyl group (P = 0.002). It is possible to quantify such episodic EEG patterns during general anaesthesia and in this study noxious stimulation tended to reduce the prevalence of these patterns.

Characterisation of vitamin B12 immunoaffinity columns and method development for determination of vitamin B12 in a range of foods, juices and pharmaceutical products using immunoaffinity clean-up and high performance liquid chromatography with UV detection.

New rapid and simpler procedures, using immunoaffinity columns, have been developed for the determination of vitamin B12 in a range of samples including three different US National Institute of Standard and Technology (NIST) Reference Materials, infant formula, powdered energy drinks and bars, wheat breakfast cereal, carbonated soft drinks, fruit juices and vitamin B12 tablets. The procedures involved extraction of vitamin B12 using water or sodium acetate buffer and enzyme digestion (using pepsin or alpha-amylase, or both) if necessary. The extract was clarified and passed through "EASI-EXTRACT Vitamin B12", an immunoaffinity column containing monoclonal antibody with high affinity and specificity to vitamin B12. Subsequently, the vitamin B12 immunoaffinity column was washed with 10 ml water and the vitamin B12 was released from the column with 3 ml methanol. Following evaporation, the samples were reconstituted in mobile phase and analysed by HPLC-UV at 361 nm on an ACE 3AQ analytical column using a gradient elution consisting of 0.025% trifluoroacetic acid in water and acetonitrile. Analysis of three types of NIST Standard Reference Materials in triplicate demonstrated the results of the immunoaffinity column method were comparable to microbiological assay results. Method repeatability was determined for all samples analysed and ranged between 0.8 and 10%, demonstrating the method was repeatable with complex matrices (NIST 2383) containing low levels of vitamin B12 (0.44 microg per 100 g), as well as simpler matrices, such as vitamin tablets containing high levels (2000 microg per 0.849 g) of vitamin B12.

Myocilin protein levels in the aqueous humor of the glaucomas in selected canine breeds.

OBJECTIVE: To compare aqueous humor myocilin protein levels in dogs with the primary glaucomas to those with the secondary glaucomas, primary cataracts, and diabetic cataracts. MATERIALS AND METHODS: Four groups were selected, based on diagnosis by the attending veterinary ophthalmologists and included: primary glaucoma (primary open-angle glaucoma (POAG) and primary closed angle glaucoma (PCAG); n = 155); secondary glaucoma (n = 94); primary (presumed inherited) cataract (n = 142), and diabetic cataract (n = 83). A total of 474 samples (187 males, 263 females, 24 unreported) with average ages of 117 months for the males and 101 months for the females were analyzed. Myocilin protein was measured using the Coomassie staining and Western blot methods relative to a myocilin control. RESULTS: Differences were seen between nonglaucomatous (cataractous) and glaucomatous dogs with myocilin levels in glaucomatous eyes being many times higher than those in the cataractous dogs. Primary glaucomatous dogs were found to have an aqueous humor myocilin protein level of 17.30 +/- 1.03 units. Secondary glaucomas had the highest level of myocilin in the aqueous humor with 19.27 +/- 1.41 units. Diabetic cataractous dogs had the lowest levels of myocilin reported with 6.60 +/- 0.88 (mean +/- SEM) units. Normal (cataractous) dogs had a myocilin level in the aqueous humor of 8.05 +/- 0.86 units. CONCLUSION: Aqueous humor protein levels were elevated, relative to the myocilin control, in both the primary and secondary glaucoma groups compared to the cataract and diabetic cataract groups. Like in the Beagle POAG, aqueous humor myocilin protein levels are increased. Further studies are indicated to investigate the exact role of the aqueous humor myocilin protein in the genesis in increased IOP in these primary glaucomatous breeds.

Aqueous humor myocilin protein levels in normal, genetic carriers, and glaucoma Beagles.

OBJECTIVE: The gene (myocilin: MYOC) has been attributed to be involved in over 6% of inherited types of human glaucoma, the highest correlation for any gene to date. This study determines myocilin protein levels in the aqueous humor (AH) of normal laboratory quality, genetic carrier (offspring of normal laboratory quality and POAG Beagles), and primary open angle glaucoma (POAG) Beagles. MATERIALS AND METHODS: Eighteen dogs were used and classified as either normal, carrier or having mild, moderate or advanced POAG. A 0.1 mL sample of AH was drawn from the anterior chamber of each dog in the study and frozen on dry ice. A modified Coomassie stain and Western blot, using a polyclonal rabbit antihuman myocilin antibody (Santa Cruz Biotechnologies, Santa Cruz, CA), was run on each sample to compare the myocilin levels. A purified human trabecular meshwork excreted myocilin protein sample was used as a control (Alcon Research Laboratories, Fort Worth, TX) and its band/densitometry measurement was defined as one unit of myocilin for comparisons. RESULTS: Comparisons of AH myocilin levels differed among normal laboratory quality, genetic carrier, and POAG Beagles at different stages of the disease. In the normal laboratory, Beagles the AH myocilin measured 0.817 +/- 0.075 units (mean +/- SEM); in the carrier Beagles the AH myocilin was 3.117 +/- 0.290 units. As POAG progressed, myocilin protein levels also increased to 6.097 +/- 0.810, 8.844 +/- 1.079, and 17.228 +/- 1.198 units in the early, moderate, and advanced forms, respectively. Overall comparisons between normal, carrier and all POAG Beagles combined showed significant differences (P < 0.0010). Individual comparisons between normal and carrier eyes showed significant differences (P < 0.0193). Comparisons between normal and all POAG eyes also showed significant differences (P < 0.0426). CONCLUSION: This study shows myocilin protein is present in normal Beagles, markedly increased in POAG Beagles, and mildly increased in genetic carrier Beagles. There is a strong correlation between amounts of AH myocilin protein and the presence and severity of POAG. The exact role of AH myocilin levels in the genesis of ocular hypertension remains unresolved, but myocilin may adversely affect AH outflow.

Immunolocalization of myocilin protein in the anterior eye of normal and primary open-angle glaucomatous dogs.

OBJECTIVE: The presence of myocilin was investigated in a colony of Beagles, a canine model for inherited primary open-angle glaucoma (POAG). The myocilin protein was localized in the normal and glaucomatous canine eyes by immunohistochemistry and immunocytochemistry. METHODS: Paraffin- and plastic-embedded specimens from the anterior uveas of 10 Beagles with inherited glaucoma (3 months to 13 years old) and 6 age-matched normal dogs were sectioned, and were then incubated with primary antibody, rabbit polyclonal antihuman MYOC IgG, overnight at 4 degrees C. Specimens were incubated with secondary antibody with one of the following: biotinylated link followed by peroxidase-labeled streptavidin and then by substrate-chromogen for light microscopy; fluorescent marker Texas red; or 18 nm colloidal gold-labeled goat antirabbit IgG for transmission electron microscopy. RESULTS: With normal, pre- and early glaucomatous canine specimens, cell membranes of smooth muscle cells of the iris and ciliary body stained positively, as well as most resident stromal and vascular endothelial cells. The cytoplasm of cells within the nonpigmented ciliary epithelium of the ciliary body processes stained intensely, being weaker along the pars plana. Trabecular meshwork (TM) cells and surrounding extracellular matrix labeled, as well as the sclera adjacent to the angular aqueous plexus. In specimens with moderate and advanced glaucoma, greater intensity of staining was observed within TM cells and adjacent sclera, and portions of the nonpigmented epithelium of the ciliary processes. Fibrinous material labeled intensely within the posterior chamber. CONCLUSIONS: Myocilin in the normal and glaucomatous canine eye was successfully immunolocalized. These findings with regard to the normal eye are nearly identical to those previously reported in humans, and support the original hypothesis that there is an increase in both accumulation and localization of myocilin in glaucomatous canine eyes. It also supports the possibility that changes in the activity of myocilin within the aqueous humor outflow pathway of individuals with spontaneous glaucoma are associated with the rise of intraocular pressure and subsequent development of this disease, but may not be the primary event in the initial raise in intraocular pressure in POAG in the Beagle.

A variant epidermal growth factor receptor protein is similarly expressed in benign hyperplastic and carcinomatous prostatic tissues in black and white men.

BACKGROUND AND OBJECTIVE: Anti-epidermal growth factor receptor strategies are now established in cancer treatment We have recently described the presence of EGFRvIII (a variant EGFR) in prostatic tumours from UK white men and this is now a target for anti-prostate cancer treatments. However, there has been no report on the expression of this abnormal protein in black men. MATERIALS AND METHODS: We determined EGFRvIII expression in sections of normal, benign hyperplastic (BPH) and carcinomatous (CaP) prostatic archival tissues from Nigerian men and UK white men using streptavidin immunohistochemical techniques. The EGFRvIII immunoreactivity was scored visually using a semi-quantitative method and the results compared statistically. RESULTS: EGFRvIII expression increased with increasing malignancy in both study populations (CaP > BPH > Normal p, <0.0001). Furthermore, EGFRvIII expression was similar in both BPH and CaP tissues in black and white men (p, 0.86 and 0.31 respectively). CONCLUSION: These results demonstrate that EGFRvIII immunoreactivity in prostatic tumours in black men is similar to that in white men. Anti-cancer treatments directed at the EGFRvIII should be equally effective in men from both subpopulations.

Abbreviated method of determining vein volume in balloon-controlled vein ablation.

Traditional surgical ligation and stripping for the treatment of saphenous vein incompetence has been replaced by minimally invasive alternative treatments during the last five years. Endovenous ablation with radiofrequency (RP) and laser (EVL) have proven to be safe, durable, and widely accepted by patients. Catheter-delivered sclerotherapy (CDS) with foam and liquid for ablation of the great saphenous vein is also under investigation. In this technique, vein volume must be measured accurately by ultrasound just prior to the procedure and can require up to 11 diameter measurements. The purpose of this study was to identify an abbreviated method of determining vein volume to expedite associated endovenous procedures. Seventy-five veins were treated in 55 subjects with catheter-directed sclerotherapy in a three-center clinical study using a standardized protocol. Vein volume was carefully calculated by determining vein diameter over the Treatment Length in 4 cm intervals. These measurements were compared to vein volume calculations where only three measurements were taken. Our results suggest that the abbreviated method is capable of significantly reducing the number of diameter measurements without sacrificing accuracy. We found the method produced a vein volume that fell within 1 mL or 15% of the actual vein volume in 80% of cases. The abbreviated method cannot be used with accuracy in veins that are Erratic.

Effect of lacrimal punctal occlusion on tear production and tear fluorescein dilution in normal dogs.

OBJECTIVE: To evaluate effects of lacrimal punctal plugs positioned in either the upper, lower, or combination of upper and lower lacrimal canaliculi on plug retention and tolerance; tear production, as measured by the Schirmer tear test; and the dilution of fluorescein within the tear film in normal dogs. MATERIAL AND METHODS: Lacrimal punctal plugs were positioned in the lower, upper, or combination of lower and upper plugs in six laboratory-quality Beagles under topical anesthesia. Retention of plugs was evaluated daily from 8 to 23 days by visual inspection and slit-lamp biomicroscopy. Schirmer tear tests (STT 1 without topical anesthesia) were performed at 48-h intervals. Dilution of fluorescein was determined at 5- and 45-min post-fluorescein instillations once weekly. RESULTS: Lacrimal punctal plugs of 0.4 and 0.6 mm in diameter were retained for 14 (lower plugs: 100%) and 23 days (75%), and for the upper plugs at 8 days less often (75%), and were infrequently locally nonirritating. Combination of lower and upper plugs seemed to adversely affect retention of either plug. When loss of the plugs occurred, a next larger size plug was necessary suggesting some stretching of the lacrimal canaliculi occurred. Pre- and postplug placement STT results indicated no change with lower and combination lacrimal punctal plugs, but decreased levels following upper lacrimal punctal plugs. Tear fluorescein levels at 5 and 45 min in control eye (no punctum plugs) were 3.39% and 0.14%, respectively. With lower, upper, and the combination of lower and upper lacrimal puncta plugs, tear fluorescein levels at 45 min were higher than the controls (lower: 0.76%; upper: 0.45%, and combination 0.56%). CONCLUSION: Lacrimal punctal silicone plugs are retained for 8-23 days in the lower, upper, and combined lower and upper canaliculi at high rates. Effects on STT levels appear limited. Fluorescein within the tear film persists longer with all different positioned lacrimal punctum plugs than in the control eyes.

Inheritance of cataract in the Bichon Frise.

OBJECTIVE: To determine the mode of inheritance of cataract formation in the Bichon Frise. MATERIALS: Thirty-six closely related Bichon Frise dogs in a pedigree of 61 dogs were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy over a period of 10 years. RESULTS: Of the 61 related dogs, 36 were examined repeatedly. Twelve cataractous dogs were diagnosed (three males and nine females). Cataractous dogs resulted from matings between unaffected parents, and when one parent was cataractous and the other parent was unaffected. Age at onset of cataract formation ranged from 18 to 160 months. Available information suggests that the cataracts are inherited as an autosomal recessive trait. CONCLUSION: Cataracts appear inherited in the Bichon Frise as an autosomal recessive trait. Additional cataract x cataract matings are necessary to confirm the autosomal recessive heredity.