Endoscopic and surgical treatment of non-neoplastic proximal duodenal ulceration in dogs, and anatomical study of proximal duodenal vascularisation.

OBJECTIVES: Proximal duodenal ulceration is often characterised by continuous bleeding, and treatment is challenging. The aims of this study were to investigate the role of vascularisation in proximal duodenal ulceration and describe clinical aspects, endoscopic features and treatment in dogs. MATERIAL AND METHODS: Polyurethane foam casts of gastroduodenal vessels were obtained from five dogs which had died from disorders unrelated to the digestive system. In addition, 12 dogs having proximal duodenal ulcers diagnosed by endoscopic examination were enrolled in a treatment trial. After the endoscopic diagnosis of a duodenal ulcer, all the dogs were treated medically and, in the absence of resolution, were subsequently treated by endoscopic electrocauterisation or by surgery. RESULTS: A submucosal vascular network was evident in all the casts, with a prominent venous plexus seen exclusively in the first half inch of the duodenum. In clinical cases, on endoscopic examination, the duodenal ulcer was located at the proximal part of the duodenum, involving the mesenteric portion of the wall. The dogs not responding to medical treatment (6/12) were treated with endoscopic electrocauterisation, surgical coagulation or resection of the proximal duodenal portion. All the dogs survived until discharge, and the median survival time following discharge was 107.5 days. CLINICAL SIGNIFICANCE: Based on the anatomical details highlighted in this study, the continuous bleeding observed in our patients may have been due to the prominent venous plexus evidenced at the level of the proximal duodenum. Surgical and endoscopic treatments in six patients resolved the ulcer bleeding with no recurrences noted during follow-up.

A retrospective study on bone metastasis in dogs with advanced-stage solid cancer.

OBJECTIVES: To review clinical characteristics, treatment, outcome and prognostic factors in dogs with solid cancer-bearing bone metastases. MATERIALS AND METHODS: Records were reviewed from dogs with histologically-proven solid cancer and bone metastases. Clinicopathologic variables, bone metastases characteristics and skeletal-related events were recorded. Endpoints were time to bone metastases and survival. RESULTS: Fifty dogs were included, 20 of them with synchronous and 30 of them with metachronous bone metastases. In the latter group, median time to diagnosis of bone metastases was 210 days (range, 30 to 1835). Most common primary cancer locations included mammary gland (n=6), spleen (n=5) and tonsil (n=5). Most common histotypes were carcinoma (n=32) and hemangiosarcoma (n=10). Nineteen dogs had multiple bones involvement, with humeri and vertebrae more commonly affected. Twenty-four dogs received antitumoural therapy, five symptomatic treatment and 21 were not treated. Overall median survival after bone metastases diagnosis was 30 days (range, 11 to 49); 83% of dogs died because of skeletal-related events. Lack of antitumoural therapy was significantly associated with shorter survival (hazard ratio: 2.7; 95% confidence interval: 1.3 to 5.6) and with increased risk of skeletal-related death (hazard ratio: 3.3; 95% confidence interval: 1.4 to 7.4). Dogs with endocrine/neuroendocrine tumours (odds ratio: 8.8; 95% confidence interval: 1.2 to 63.9), without appendicular metastases (odds ratio: 5.1; 95% confidence interval: 1.0 to 25.8), without extra-skeletal metastases (odds ratio: 5.2; 95% confidence interval: 1.1 to 24.5) and receiving antitumoural therapy (odds ratio: 14.8; 95% confidence interval: 1.7 to 131.4) had an increased chance of surviving more than 100 days. CLINICAL SIGNIFICANCE: Bone metastases in dogs with solid cancers are associated with poor prognosis and a high risk of skeletal-related events. Treatment appears to have an impact on survival.

Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity.

New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

Effects of 2% ibopamine on pupil, refraction, anterior segment anatomy and intraocular pressure.

The aim of the study was to determine the effects of a dopaminergic drug, 2% ibopamine, on the pupil, intraocular pressure and other ocular and ultrasound biometric variables. Thirty healthy subjects and 15 patients with primary open-angle glaucoma, aged from 40 to 78 years (mean age: 59.2 +/- 11), were included in two prospective open controlled trials. In the first, the mydriatic effect of 2% ibopamine and its inhibition and reversibility were evaluated in 15 healthy subjects using the alpha1-adrenergic drug, 0.5% dapiprazole. In the second, refraction, visual acuity, pupil diameter, intraocular pressure and 5 A-scan ultrasound biometric variables were evaluated in 15 healthy subjects and in 15 glaucoma patients. As early as forty min after administration of 2% ibopamine, a marked mydriatic effect (7.3 vs 3.9 mm; P < 0.0001), which was completely inhibited or reversed by 0.5% dapiprazole, was detected. The drug induced no changes in refraction, visual acuity or A-scan ultrasound biometric variables in any of the subjects examined. In healthy subjects, the intraocular pressure values were not changed to a statistically significant extent (13.8 vs 14.8 mm Hg; P = 0.668), whereas a slight, though significant, hypertensive effect (24 vs 22.2 mm Hg; P = 0.002) was observed in the glaucoma patients. The study confirms the intense mydriatic effect of 2% ibopamine with no changes in refraction, visual acuity or A-scan ultrasound biometric variables. The drug has no effect on intraocular pressure in healthy subjects, but induces a significant hypertensive effect in patients with initial glaucoma. This characteristic could be used for early diagnosis of primary open-angle glaucoma.

Ultrasound biomicroscopy and corneal endothelium in Nd:YAG-laser iridotomy.

BACKGROUND AND OBJECTIVE: Thirty eyes affected by angle-closure glaucoma that had undergone YAG-laser iridotomy were studied to evaluate variations of central anterior chamber depth, width of the angle, and loss of endothelial cells after laser treatment. PATIENTS AND METHODS: These parameters were determined before and after iridotomy: endothelial cell count using a "non-contact" specular biomicroscope, and anterior chamber depth and angle width using ultrasound biomicroscopy (UBM). The width of the iridotomy and the distance of the iridotomy from the scleral spur and from the corneal endothelium were also measured by UBM, after laser treatment. RESULTS: Results confirmed that, after iridotomy, there is not a significant variation in the central depth of the anterior chamber: it goes from 2.02 mm pre-laser to 2.07 +/- 0.38 mm post-laser. There is, however, a statistically significant increase in the angle (P < .001), which goes from 10.69 +/- 8.88 degrees (0.109 +/- 0.07 mm) to 21.03 +/- 11.28 degrees (0.183 +/- 0.09 mm). The mean dimension of the iridotomies was 0.46 +/- 0.13 mm. The mean endothelial cell count was 55.8 +/- 4.08 cells per linear millimeter before laser treatment and 47.01 +/- 5.39 cells per linear millimeter afterward (P <.001). CONCLUSION: This study confirms that YAG-laser iridotomy leads to a reduction in the average endothelial cell density. The loss of these cells is inversely proportional to the distance of the iridotomy from the endothelium and the scleral spur.

The nerve fibre layer in ocular hypertension. Preliminary results.

A group of healthy subjects (IOP < 22 mmHg) and a simple ocular hypertension group (IOP > or = 22 mmHg) were examined with a view to checking if there were any differences between their nerve fibre layers. Results indicate thinner fibres in the ocular hypertensives significantly correlative with pressure increase. Among the two groups, some corresponding fibre thicknesses were found.

Ocular hypotensive activity of pirbuterol eye drops in rabbits.

The IOP-lowering effect of pirbuterol, a beta-2 adrenergic agonist, was studied in rabbits. In normotensive rabbits, pirbuterol 0.5% eye drops reduced IOP by 20-25%. In ocular hypertensive rabbits (by glucose 5% venous infusion), pirbuterol reduced IOP by 20% (0.1% concentration) to 40% (0.5% and 1% concentration). A slight decrease in the effect was noticed after seven days of treatment.

Subconjunctival THC:YAG laser sclerostomy for the treatment of glaucoma: preliminary data.

A subconjunctival thermal sclerostomy was performed using the recently developed THC:YAG laser in 33 eyes with a variety of glaucomas in which, in most cases, neither medical therapy nor previous procedures had been successful in controlling intraocular pressure (IOP). The mean preoperative IOP was 27.5 +/- 7.5 mm Hg with maximum medication. The laser procedure was quick and easy, with minimal manipulation of tissues; complications were clinically insignificant. The day after the operation, 23 eyes had an IOP less than 18 mm Hg; in the other 10, it was unchanged. In most of the eyes, an obvious filtering bleb developed at the site of the sclerostomy. The internal opening of the sclerostomy was visible on gonioscopy, except in five cases, in which it was plugged by a fold of the iris root. One year after the operation, IOP was controlled in three eyes without medication and in 18 with medication. IOP remained uncontrolled in the remaining 12 eyes.

Prevention of surgically induced miosis by diclofenac eye drops.

In this investigation, a rabbit model was used to study the effectiveness of topical diclofenac sodium in the prevention of miosis induced by manipulation of the ocular structures. In untreated rabbit eyes, paracentesis of the anterior chamber induced a 25% narrowing of the pupil. In atropine-treated rabbit eyes, the absolute pupil diameters were larger, but the pupil still contracted, resulting in a postoperative diameter of 6.5 mm. Pretreatment with diclofenac 0.1% eye drops effectively inhibited paracentesis-induced miosis; the postoperative pupil narrowing amounted to only 9% of the original diameter in both untreated and atropine-treated eyes. With a combined topical application of atropine and diclofenac, the mean pupil diameters after paracentesis were as large as 8.7 mm. Diclofenac seems to be a promising drug for the maintenance of mydriasis during eye surgery.

Effects of the association of alpha and beta-blocking agents in glaucoma.

Twenty patients with POAG and early visual field changes, already under treatment with 0.5% timolol were randomly assigned to additional topical treatment with 0.5% dapiprazole or placebo. After six months of treatment no differences were observed between the groups for what concerns visual field. After six months of treatment visual field, visual flicker discrimination and contrast sensitivity proved to be constant without differences between the groups. On the contrary, mean IOP was found to be significantly lower in the dapiprazole group.

Intraocular-pressure-lowering effect of low-dosage combination of guanethidine and terbutaline in rabbit.

A low dosage combination of terbutaline plus guanethidine was applied topically to the eyes of rabbits with experimentally induced ocular hypertension, markedly lowering intraocular pressure. The effect of this combination is markedly greater than that produced separately by the two components at corresponding dosages and seems to be due to a true synergistic phenomenon. The low-dosage combination of terbutaline and guanethidine appears to be well tolerated, very potent and effective as a topical ocular hypotensive agent.

Comparison of the effects of nine beta-adrenergic blocking agents on intraocular pressure in rabbits.

The intraocular pressure lowering effects of nine beta-adrenergic receptor blocking agents were compared using two different models of experimental ocular hypertension in rabbits. All the nine drugs possess, to different extents, a clear pressure-lowering action after topical administration into the conjunctival sac. For potency and duration of action, the best results were obtained with timolol and sotalol. Pindolol, oxprenolol, practolol, and propranolol are also fairly potent while less impressive effects were produced by atenolol, butidrine, and metoprolol. With the exception of propranolol, all the drugs were well tolerated by the ocular tissues.

Glaucoma and quality of the life.

A questionnaire was prepared and given to 332 subjects who passed through our Institute for Glaucoma with the aim of evaluating their quality of life. The diagnosis of glaucoma is associated with a diminished quality of life in a considerable percentage of the interviewed subjects. The patients are troubled most of all by the inconvenience of the treatments and the fear of visual compromission. Mitotic therapies, polytherapies and systemic therapies are the less agreeable of them. Of the therapy in itself, the most disagreeable aspects are the frequency and timetable of the medications. No quality of life differences were mentioned by surgically treated patients nor those on solely pharmacological treatment.

Experimental corticosteroid ocular hypertension in the rabbit.

Weekly subconjunctival injections of 4mg repository betamethasone, repeated over three weeks, produced a sustained increase of intraocular pressure (IOP) in 96% of the treated rabbits. Treatment was generally well tolerated and important systemic toxic effects were present only in a few animals. The ocular hypertension so obtained was constant, well reproducible and sensitive to antiglaucoma drugs. The authors believe they have developed an animal model which is very suitable for testing the pressure-lowering effect of drugs and for other studies on ocular hypertension and glaucoma.

Effects of dapiprazole on pupillary size and intraocular pressure in rabbits.

The effects of 3-[2-[4-(2-methylphenyl)-1- piperazinyl]ethyl]-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridine HCl (dapiprazole), a new drug with alpha-adrenergic blocking properties, on pupillary diameter and intraocular pressure have been studied in rabbits. Following i.v. administration, a reduction of intraocular pressure is observed at doses devoid of activity on pupillary diameter. Following topical application, a miotic and ocular hypertensive action was observed at the same doses; the hypotensive action is produced in both normal rabbits and in rabbits with water load- or corticosteroid-induced ocular hypertension. Contact lenses increase the duration of effects of dapiprazole. These results suggest a potential interest of dapiprazole in glaucoma, with particular reference to the topical treatment of angle-closure glaucoma.

Ocular hypotensive action of labetalol in rabbit and human eyes.

The ocular hypotensive action of labetalol, a drug endowed with alpha- and beta-adrenergic receptor-blocking properties, was studied in both rabbit and human eyes. In the rabbit, using two different models of experimentally induced ocular hypertension, an impressive decrease of IOP was seen after topical administration of the drug. In this species labetalol was found to be at least as effective as timolol and more active than pilocarpine or propranolol. In human eyes suffering from glaucoma, however, its effectiveness was much less evident and clearly inferior to that of timolol.

Epidemiology of angle-closure glaucoma: prevalence, clinical types, and association with peripheral anterior chamber depth in the Egna-Neumarket Glaucoma Study.

OBJECTIVE: To assess the prevalence of primary angle-closure glaucoma (PACG), the frequency of its different clinical presentations, and its association with peripheral anterior chamber depth in a defined population in Northern Italy. DESIGN: Cross-sectional epidemiologic study in a defined population. PARTICIPANTS: All subjects resident in the Egna-Neumarkt area of the South Tyrol Region (Northern Italy) and more than 40 years of age were invited to undergo an ophthalmologic examination. INTERVENTION: After the screening examination, subjects with suspected glaucoma were re-examined at the screening center to confirm the diagnosis. All cases that still proved suspect after the second examination underwent a third phase of investigations and were classified as healthy or as definitely glaucomatous. Each subject was examined according to a standard protocol, including medical history interview, refraction and visual acuity determination, ocular biomicroscopy, evaluation of peripheral anterior chamber depth by means of the Van Herick method, applanation tonometry, optic disc evaluation, and computerized perimetry. Gonioscopy was not performed during initial screening but only in all selected patients in the second and third phases of investigations. The diagnosis of PACG was made on the basis of the concomitant presence of at least two of the following criteria: intraocular pressure > or = 22 mmHg, glaucomatous optic disc abnormalities, glaucomatous visual field defects. In addition, biomicroscopic or gonioscopic evidence of angle closure was also necessary. MAIN OUTCOME MEASURES: Percentage distribution of peripheral anterior chamber depths, prevalence of angle-closure glaucoma, and frequency of the different PACG clinical presentations. RESULTS: Four thousand two hundred ninety-seven subjects were examined (73.9% overall participation rate). The peripheral depth of the anterior chamber according to the Van Herick method was grade 2 in 14.7%, grade 1 in 2.5%, and grade 0 in 0.3% of the population. The overall prevalence of angle-closure glaucoma was 0.6% (26 cases). Five of these were cases of previous acute attacks resolved by therapy, three were cases of chronic angle-closure after acute attacks, three were intermittent angle-closure glaucomas, and 15 were chronic angle-closure cases. CONCLUSIONS: Occludable angles were more frequent than in other white populations previously studied. The prevalence of PACG is not as low as is usually believed; this type of glaucoma accounts for more than a quarter of all glaucomas found in the Egna-Neumarkt population. The most frequent clinical presentation is chronic angle-closure glaucoma.

Prevalence of glaucoma and intraocular pressure distribution in a defined population. The Egna-Neumarkt Study.

OBJECTIVE: The purpose of the study is to assess the prevalence of various types of glaucoma and to determine the intraocular pressure (IOP) distribution in a defined population in an Italian rural community. DESIGN: A cross-sectional epidemiologic study in a defined population was planned. After the screening examination, the subjects with suspected glaucoma were re-examined at the screening center in order to confirm the diagnosis. All cases that still proved suspect after the second examination underwent a third phase of investigations at the Ophthalmologic Division of Bolzano Hospital, and were classified as healthy or definitely glaucomatous. PARTICIPANTS: All subjects residing in the Egna-Neumarkt area of Alto Adige region (Northern Italy) and over 40 years of age were invited to undergo an ophthalmologic examination. INTERVENTION: Each subject was examined according to a standard protocol, including computerized perimetry, applanation tonometry, evaluation of anterior chamber depth and optic disc, and a medical history interview. The diagnosis of glaucoma was based on the presence of at least two of the following criteria: IOP > or = 22 mmHg, glaucomatous optic disc abnormalities, and glaucomatous visual field defects. Ocular hypertension was defined as IOP > or = 22 mmHg without visual field or glaucomatous optic disc abnormalities. MAIN OUTCOME MEASURES: Participation rate, mean IOP, prevalence of glaucoma (primary open-angle glaucoma, primary angle-closure glaucoma, normal-tension glaucoma, secondary glaucoma), and ocular hypertension were determined. RESULTS: Of a total of 5816, 4297 subjects were examined (73.9% overall participation rate). Intraocular pressure showed a Gaussian-like distribution curve skewed to the right. Mean IOP increased with age, and was slightly higher in men (15.14 mmHg) than in women (14.94 mmHg). The overall prevalences of ocular hypertension, primary open-angle glaucoma, primary angle-closure glaucoma, and normal-tension glaucoma were 2.1%, 1.4%, 0.6%, and 0.6%, respectively. Only 28 of 210 patients with glaucoma or ocular hypertension had been diagnosed prior to the screening. CONCLUSIONS: The distribution of IOP and the prevalence of the different types of glaucoma were similar to those found in other white populations.