Bilateral congenital lacrimal fistula in a Brown Swiss bull

A five-year-old Brown Swiss bull was referred to the Department of Farm Animals, University of Zurich, because of bilateral epiphora that was unresponsive to treatment. Clinical examination revealed a fistulous opening medial to the medial canthus of both eyes and mucopurulent discharge from both openings. Attempts to flush the nasolacrimal duct via the lacrimal points resulted in the fluid exiting via the fistulous opening. Retrograde flushing of the nasolacrimal duct from the nasolacrimal opening resulted in the flush fluid flowing back out the nasolacrimal opening. Bilateral lacrimal fistula medial to the medial canthus of the eye was diagnosed based on the findings. The same anomaly was diagnosed a year later in 4 related female animals referred to our Department for other reasons. Three of the cases were sired by the bull described above and one was sired by his half-brother. Therefore, an autosomal recessive mode of inheritance of this anomaly was assumed. Clinical, epidemiological and molecular studies of the offspring of both bulls are underway to further investigate this anomaly

Corneal collagen cross-linking as treatment for infectious and non-infectious corneal melting in cats and dogs: results of a prospective, non-randomized, controlled trial

OBJECTIVE. UV-A/Riboflavin crosslinking of corneal collagen fibers (CXL) is a highly promising therapy for corneal melting in humans. A prospective interventional, non-randomized, controlled study was conducted to compare the stabilizing effect of CXL treatment on melting keratitis in dogs and cats and the complication rate of CXL to those of standardized intensive medical treatment. PROCEDURES. Forty-nine eyes with melting keratitis were included in the study between October 2009 and October 2012. All eyes were treated according to the same medical treatment protocol. Nineteen eyes were CXL-treated and 30 eyes were not. Follow-up included slit-lamp examination, fluorescein staining, ulcer size measurement, stromal stability evaluation, photographic documentation and documentation of complications. RESULTS. Five of 19 eyes in the CXL group and 9/30 eyes in the control group required rescue stabilization due to continued melting. Seven of the 9 control group corneas stabilized after rescue CXL treatment. At initial presentation, the ulcers in the canine CXL group were significantly deeper and larger than in the control group. Ulcer deepening during follow-up was more pronounced in the canine control group than in the canine CXL group. CXL treatment related complications were not observed. CONCLUSIONS. Based on the similar failure rates in the control and CXL treatment groups despite the poorer initial situation in the CXL group, the tendency for the ulcers in the control group to deepen and the stabilization of all corneas receiving CXL rescue treatment, we believe that CXL has its place as an adjunctive therapy for melting keratitis in veterinary ophthalmology

Bilateral congenital lacrimal fistula in a Brown Swiss bull

A five-year-old Brown Swiss bull was referred to the Department of Farm Animals, University of Zurich, because of bilateral epiphora that was unresponsive to treatment. Clinical examination revealed a fistulous opening medial to the medial canthus of both eyes and mucopurulent discharge from both openings. Attempts to flush the nasolacrimal duct via the lacrimal points resulted in the fluid exiting via the fistulous opening. Retrograde flushing of the nasolacrimal duct from the nasolacrimal opening resulted in the flush fluid flowing back out the nasolacrimal opening. Bilateral lacrimal fistula medial to the medial canthus of the eye was diagnosed based on the findings. The same anomaly was diagnosed a year later in 4 related female animals referred to our Department for other reasons. Three of the cases were sired by the bull described above and one was sired by his half-brother. Therefore, an autosomal recessive mode of inheritance of this anomaly was assumed. Clinical, epidemiological and molecular studies of the offspring of both bulls are underway to further investigate this anomaly

Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

Measuring Spirituality as a Universal Human Experience: A Review of Spirituality Questionnaires

Spirituality is an important theme in health research, since a spiritual orientation can help people to cope with the consequences of a serious disease. Knowledge on the role of spirituality is, however, limited, as most research is based on measures of religiosity rather than spirituality. A questionnaire that transcends specific beliefs is a prerequisite for quantifying the importance of spirituality among people who adhere to a religion or none at all. In this review, we discuss ten questionnaires that address spirituality as a universal human experience. Questionnaires are evaluated with regard to psychometric properties, item formulation and confusion with well-being and distress. Although none of the questionnaires fulfilled all the criteria, the multidimensional Spiritual Well-Being Questionnaire is promising

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy.

The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer's test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels

Direct detection of Ehrlichia canis by PCR in the conjuncti- va of a dog with bilateral anterior uveitis

The following report describes the direct detection of Ehrlichia canis by real-time PCR in the conjunctiva of a 1-year-old female Maltese dog. After being imported from Brazil, the dog was presented because of anorex- ia, dehydration, fever and palpable mandibular lymph nodes. A few days later, the dog developed bilateral blepharospasm, photophobia and anterior uveitis. Monocytic ehrlichiosis was diagnosed by a positive PCR result and the detection of IgM and IgG anti- bodies. Because of the massive uveitis a conjunctival sample was taken with a cytobrush, which also tested positive for Ehrlichia canis DNA by real-time PCR. Only one week after starting treatment with systemic doxycycline and local anti-inflammatory and cyclo- plegic therapy the dog recovered from systemic and eye diseases. After therapy the follow-up examination revealed a full remission of clinical and hematological parameters and a negative PCR result. Der folgende Bericht beschreibt den direkten Nach- weis von Ehrlichia canis mittels Real-Time-PCR in der Bindehaut einer 1-jährigen Malteserhündin. Kurz nach dem Import aus Brasilien wurde der Hund we- gen Anorexie, Dehydration, Fieber und tastbaren Mandibularlymphknoten vorgestellt. Ein paar Tage später entwickelte der Hund bilateralen Blepharospas- mus, Photophobie und Uveitis anterior. Die Diagnose «monozytären Ehrlichiose» wurde durch eine positive PCR und den Nachweis von IgM-und IgG-Antikör- pern gestellt. Aufgrund der massiven Uveitis wurde ein Cytobrush aus der Konjunktiva entnommen und ebenfalls mittels Real-Time-PCR positiv auf Ehrlichia canis-DNA getestet. Nur eine Woche nach Thera- piebeginn mit Doxycyclin, entzündungshemmen- den Präparaten und Zykloplegika verschwanden alle klinischen Symptome. Eine Verlaufskontrolle nach Therapieende ergab eine vollständige Remission der klinischen und hämatologischen Parameter und ein negatives PCR-Ergebnis. Keywords: Ehrlichia canis, cytobrush, real-time PCR, conjunctiva, uveiti

Effects of topical administration of 1% brinzolamide on intraocular pressure in clinically normal horses

Reasons for performing study: Only few drugs with limited efficacy are available for topical treatment of equine glaucoma. Objective: To evaluate the effect of topical administration of 1% brinzolamide on intraocular pressure (IOP) in clinically normal horses. Methods: Healthy mature horses (n = 20) with normal ocular findings, were studied. The IOP was measured 5 times daily (7000, 1100, 1500, 1900 and 2300 h) over 10 days, On Days 1 and 2, baseline values were established. On Days 3-5 one eye of each horse was treated with one drop of 1% brinzolamide every 24 h immediately following the 0700 h measurement. On Days 6-8 the same eye was treated with 1% brinzolamide every 12 h (0700 and 1900 h). Measurements on Days 9 and 10 documented the return of IOP to baseline values. Statistical analysis of the data was performed. Results: In the treated eye a significant decrease in IOP compared to baseline values was noted during both the 24 and 12 h dosing periods (P<0.001). During the once-daily treatment protocol an IOP reduction of 3.1 +/- 1.3 mmHg (14%) from baseline was recorded. During the twice-daily protocol a total IOP reduction of 5.0 +/- 1.5 mmHg (21%) was achieved. Conclusion: Intraocular pressure was significantly decreased by 1% brinzolamide in a once-daily and a twice-daily treatment protocol in normotensive eyes. These findings suggest that brinzolamide might also be effective in horses with an elevated IOP. Potential relevance: This drug may be useful for treatment of equine glaucoma