Observational study of patients switched to the fixed travoprost 0.004%/timolol 0.5% combination in Croatia.

The purpose of this study was to assess both the benefits of a 3-month travoprost 0.004%/timolol 0.5%fixed combination (trav/tim) regimen in comparison with previous medications for the control of intraocular pressure (IOP) and the tolerability of these drug regimens in glaucoma patients. An observational, non-interventional, open-label study of 406 eyes with primary open angle glaucoma and ocular hypertension was thus undertaken. One drop of trav/tim fixed combination was administered in the evening for 3 months. Patients were divided into five groups according to previous drug regimens: timolol 0.5% monotherapy; betaxolol 0.5% monotherapy; latanoprost 0.005% monotherapy; travoprost 0.004% monotherapy; and dorzolamide 2%/timolol 0.5% fixed combination. Upon medication substitution, the trav/tim fixed combination provided better IOP control and tolerability in all five patient groups. At the 3-month follow up, the mean IOP changes from previous therapy were as follows: 5.2 ± 2.7 mmHg (20.8% change) in timolol 0.5% group; 5.7 ± 2.2 mmHg (22.5% change) in betaxolol 0.5% group; 3.8 ± 2.6 mmHg (24.5% change) in latanoprost 0.005% group; 4.4 ± 2.8 mmHg (20% change) in travoprost 0.004% group; and 3.4 ± 4.1 mmHg (14.5% change) in dorzolamide 2%/timolol 0.5% fixed combination group. The difference between baseline and trav/tim combination patient satisfaction at the 3-month follow-up was significant. Thus, the trav/tim fixed combination provided better IOP control and tolerability than previous mono- or polytherapies.

Role of haematological testing: ratio values of circulating platelet aggregates in visual field loss associated with pseudoexfoliation glaucoma.

The aim of the work is to examine the role of circulating platelet aggregates (CPAs) in association with pseudoexfoliation glaucoma (PXG) and searching for visual field (VF) progression. The impact of CPAs in association with PXG and ischaemic events related to optic nerve damage and VF progression has not been so far sufficiently explained. The examination included 80 patients, of whom 35 (44 %) were men with average age of 68.3 +/- 7.0 and 45 (56 %) were women with average age of 65.7 +/- 7.0 (t = 1.66; p = 0.101). Forty of them suffered from primary open-angle glaucoma (POAG) and were included into a control (healthy) group, and 40 patients suffered from pseudoexfoliative glaucoma (PXG) and were included into the experimental group. All the examinees underwent complete ophthalmologic examination of visual acuity, ocular fundus, intraocular pressure and anterior eye segment by biomicroscopy and gonioscopy. In addition, VF examination was performed three times in six-month intervals. Laboratory testing of CPA proportion values was performed by means of Wu an Hoak method. The obtained decreased values of CPA proportion were caused by hypercoagulability of blood in PXG group resulting finally in ischaemia and hypoxia helping the progression of visual field. In conclusion, our study shows that CPA examination improves the assessment of the vascular role and PXG prognosis (Tab. 3, Ref. 30).

Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice.

Expression levels of the papain-like cysteine protease cathepsin B (Ctsb) have been positively correlated with mammary tumour progression and metastasis; however, its roles in the hallmark processes of malignant growth remain poorly defined. Using Ctsb-deficient mice we investigated tumour cell differentiation, proliferation and apoptosis in the Tg(MMTV-PyMT) mouse mammary cancer model. Absence of Ctsb significantly impaired development of high-grade invasive ductal carcinomas and reduced the metastatic burden in the lungs. Mice lacking Ctsb exhibited reduced cell proliferation in mammary carcinomas and their lung metastases. Notably, intravenous injection of primarily isolated, Ctsb-expressing tumour cells into congenic Ctsb-deficient mice revealed impaired cell proliferation in the resulting experimental lung metastases, providing evidence for the involvement of Ctsb in paracrine regulation of cancer cell proliferation. No Ctsb genotype-dependent difference in tumour cell death was observed in vivo or by treatment of isolated PyMT cancer cells with tumour necrosis factor-alpha. However, cancer cells lacking Ctsb exhibited significantly higher resistance to apoptosis induction by the lysosomotropic agent Leu-Leu-OMe. Thus, our results indicate an in vivo role for Ctsb in promoting cellular anaplasia in mammary cancers and proliferation in lung metastases.

Influence of war circumstances on tumor morphological characteristics in patients with breast cancer.

The influence of war circumstances on tumor morphological characteristics in patients with breast cancer has not been studied up to now. The aim of this study is to investigate if war circumstances have influenced breast cancer incidence. The study covered both the patients in which during a period of observation a breast cancer was diagnosed as well as those who died of the same disease in the same period. Three sources of data were used: 1) The archives of the Oncology and Radiotherapy Center of the University Hospital "Split" (UHS): hospital data of 768 patients were reviewed. The war sample consisted of 380 patients aged 59.4+/-12.1 (31 to 86) (including 5 males), whereas the pre-war sample was made up of 388 patients aged 58.4+/-12.7 (19 to 88) (including 3 males); 2) Register of death of the Pathology Department of UHS with 162 analyzed persons whose death was caused by breast cancer in the six-year period between 1988 and 1993. The list of 162 dead patients included 79 people who died from breast cancer diagnosed in that period (1988-1993) and another 83 people that had been diagnosed before that period; 3) The biopsy register of the Pathology Department of UHS with 851 breast biopsies performed between 1988 and 1993. Breast cancer is predominantly a female illness (99.1%). The war circumstances influenced the of T, N and M rate. The rate of N2, N3, Ml were conspicuously higher in the war period. There were significantly more malignant histological diagnoses found in new patients and also significantly more patients died due to breast cancer. Stress and other war circumstances undoubtedly have a negative impact on the numerous markers of breast cancer which we have proved in this study.

Visco and phacoviscocanalostomy in managing glaucoma patients.

The purpose of this study was to evaluate a nonfiltering glaucoma technique viscocanalostomy alone or in combination with small incision phacoemulzification and intraocular lens (IOL) implantation. From January 1999 to February 2001 viscocanalostomy was performed in 18 patients with medically uncontrolled primary open angle glaucoma. In 10 patients with cataract and primary open angle glaucoma combined operation phacoemulsification and viscocanalostomy was performed. The mean IOP reduction remained statistically significant after 12 months in both groups (p < 0.01). There was also a significant decrease in the antiglaucoma medications in both groups postoperatively. Perforation of trabeculo-Descemet's membrane occurred in two eyes with POAG and the procedure was completed as trabeculectomy, and those patients were excluded from the study. Good hypotensive effect with very low complications rate was achieved. Such a low complication rate makes this operation particularly attractive to surgeons who perform an increasing number of operations in outpatient's bases.

Hyperbaric oxygen therapy in two patients with non-arteritic anterior optic neuropathy who did not respond to prednisone.

Recent advances in understanding the effects of hyperbaric oxygen (HBO) on retinal anoxia gave rise to new interest in the possibility of using it as therapeutic treatment for ischemic conditions of the retina and optic nerve. Two patients with non-arteritic anterior ischemic optic neuropathy due to a high-grade ophthalmic artery stenosis were treated with HBO at 2 atm abs in an effort to increase oxygen delivery for the eye. Both patients showed marked improvements of visual acuity and visual field 3-5 months following the event. Our results are intriguing although the achieved improvement could be coincidental.

The effect of delivery on regression of abnormal cervical cytologic findings.

The purpose of this study was to determine whether abnormal antepartum cervical cytologic findings result in differing postpartum regression rates. Between 1993 and 2000, 107 pregnant women with antepartum abnormal cervical cytologic findings were identified. Papanicolaou smear data were separated into three groups by use of the CIN classification system. Postpartum regression rates of antepartum Papanicolaou smears were analyzed six months after delivery. Normalization of Papanicolaou smears in the postpartum period were observed in 50 of 107 women (46.7%). Regression of cervical cytologic findings was noted in 61 of 107 women (57%). Respectively, persistence of Papanicolaou smear was noted in 43 of 107 patients (40%). Only 3 of 107 (3%) antepartum findings progressed after delivery. Desquamation of the cervical epithelium or enhancement of a localized reparative immunologic response after vaginal delivery could play an important role in the spontaneous regression of cervical dysplasia in the postpartum period.

Circulating platelet aggregates and progression of visual field loss in glaucoma.

The aim of the study was to assess a relationship between circulating platelet aggregates (CPA) and progression of visual field loss in primary open-angle glaucoma patients. CPA was determined in 27 patients with open-angle glaucoma with nonprogressive visual field loss and 15 patients with open-angle glaucoma and progression of visual field loss. Intraocular pressure (IOP) under topical therapy was < 18 mmHg in all patients. CPA in glaucoma patients with progression of visual field loss was not significantly higher than those without visual field progression (p = 0.59). In conclusion, our study shows that increased platelet aggregability is not solely responsible for progression of visual field loss in glaucoma patients, and indicates the role of IOP in the pathogenesis of visual field loss.

Evaluation of the intraocular pressure-reducing effect of latanoprost as monotherapy in open-angle glaucoma.

Objective of this study was to evaluate the intraocular pressure-reducing effect of latanoprost as monotherapy after replacing current dual therapy in glaucoma patients. The 6-months study comprised 189 patients with primary open angle glaucoma who were treated at least 6 months with two different kind of topical medications (beta-blockers, pilocarpine, dorzolamide and brimonidine). Due to local side effects, multiple dosing regime and inadequately controlled intraocular pressure (IOP), they where switched to latanoprost 0.005% monotherapy. After switched to latanoprost, mean (IOP) was measured at baseline, after 15 days, 2 and 6 months of treatment. After six-months 178 patients had completed the study. These analyses enrolled all patients (n = 189), thus, the Intention-To-Treat (ITT) results were shown instead of the results of the reduced population. IOP was clinically importantly reduced from baseline level. Five patients had uncontrolled IOP. The difference between IOP before (21.9 +/- 2.4) and after 15 days (17.4 +/- 1.7), 2 months (16.7 +/- 1.8) and 6 months (16.6 +/- 1.4) was statistically significant (p < 0.001). 90% patients has reached target IOP < or = 18 mm. A conjunctional hyperaemia in 18 (9%), stinging and itching in 7 (4%) patients was reported. Increased iris pigmentation was seen in 3 (2%) patients. The results of this study indicate that dual therapy in open-angle glaucoma can effectively be replaced by latanoprost monotherapy in many patients.

[Snoring and obstructive sleep apnea]. / Hrkanje i opstruktivna apneja za vrijeme spavanja.

Snoring and obstructive sleep apnea are similar disorders in etiology, with differences in clinical presentation and treatment. 5-20% of young and 40-50% of older population are affected by either of these disorders. Etiology of snoring should be sought in the anatomic irregularities of commencing portions of the upper respiratory and gastrointestinal tracts, obesity, alcohol abuse, use of some medications as well as in the sleep architecture disturbance. Treatment success depends on correctly established diagnosis and precise localisation of anatomic irregularity implicated in snoring. A wide array of diagnostic tests exist some of which are mandatory while the others are used on a case-by-case basis. Treatment is either conservative or surgical. The success rate is 30-90% depending on the type and the management of disorder. An algorithm for diagnosis and treatment of snoring and obstructive sleep apnea is shown at the end of the paper.

Acute angle-closed glaucoma and meteorological factors in Split, Croatia.

This study is a retrospective analysis of medical findings of patients treated at the Department of Ophthalmology, Clinical Hospital Split, Croatia in the period of 1995-1999. Seventy-three cases of acute closed-angle glaucoma were analyzed and compared in relation to the meteorological factors--hours of sunshine, air temperature and atmospheric pressure. No significant statistical correlation was found between the development of acute closed-angle glaucoma and air temperature, atmospheric pressure and mean sunshine hours in all months, except in November (z = 2.1; p = 0.03). The mean daily sunshine hours on the day of the acute closed-angle glaucoma onset were found to be lower than the mean monthly sunshine hours. An increased incidence of acute closed-angle glaucoma was found in the the winter months (chi 2 = 14.4; p < 0.01). Seasonal variations of the incidence of acute closed-angle glaucoma in Split cannot be directly attributed to the meteorological factors, although the correlation between acute glaucoma and sunshine seems to have a slightly inverse ratio.

Syndroma: glaucoma pigmentatum primarium--pigmented glaucoma.

In this study pigmented glaucoma was diagnosed in 29 out of 4350 patients suffering from glaucoma. In clinical analysis of those cases main attention was put on Krukenberg spindle with emphasis on the process and reason of its development. In all cases of Krukenberg spindle moderate myopia and myopic astigmatism were present. The main axis of the spindle lies in the principal meridian of corneal astigmatism. The principal meridian of the anterior cornea surface corresponds with the axis of the principal meridian of the posterior corneal surface. The higher degree of astigmatism more pronounced Krukenberg spindle. This corresponds to a number of cases in which the spindle is hardly recognisable in the astigmatism, of only +/- 0.25 to +/- 0.50 Dcyl. The axis of meridian corresponds to direct astigmatism (from 110 degrees to 70 degrees). The authors conclude that there is no pigmented Krukenberg spindle without myopic astigmatism. It is for this reason and because of the inheritance factor that this type of glaucoma should be considered primary glaucoma and a separate clinical entity.

Hypertensive retinopathy and pre-eclampsia.

The aim of the study was to determine the relationship between hypertensive retinopathy and the severity of pre-eclampsia. Forty women with pre-eclampsia, mean age 29.1 (+/- 7.4; range, 19-44) years, were retrospectively analyzed. They were treated at the Department of Obstetrics and Gynecology of the Clinical Hospital Split, from January 1997 to December 1999. The mean age of gestation was 36.0 +/- 2.8 weeks (range, 28-39). Pre-eclampsia was classified according to Goecke. Based on the ophthalmoscopic fundus examinations the patients were divided into four groups, according to Keith-Wagner classification system of grading retinal changes. Of 40 analyzed women, 18 (45%) had ophthalmologically verified hypertensive retinopathy. Ten of them were classified as grade I, six as grade II and two as grade III. Twenty-two patients had mild pre-eclampsia, ten patients had moderate pre-eclampsia, and eight patients had severe pre-eclampsia. A statistically significant correlation (t-test) was found between the degree of hypertensive retinopathy and patient age, Apgar score, trophism, Goecke's index, proteinuria, systolic and diastolic pressure (P < 0.001) and edema (P = 0.01). The degree of hypertensive retinopathy was directly proportional with the severity of pre-eclampsia and significant correlation was found between them (r = 0.338, p = 0.033). These findings showed that the degree of hypertensive retinopathy in women with pre-eclampsia is a valid and reliable prognostic factor in determining the severity of the pre-eclampsia. Therefore, it can be concluded that the examination of the fundus is a valuable and necessary diagnostic procedure in pregnant women with pre-eclampsia.

Should we screen for asymptomatic left ventricular dysfunction in glaucoma patients?

BACKGROUND: The aim of the study was to assess the frequency of asymptomatic left ventricular dysfunction in primary open-angle glaucoma patients. PATIENTS AND METHODS: Two-dimensional and pulsed Doppler echocardiography of transmitral flow was performed on 31 glaucoma patients and 27 controls. RESULTS: No significant difference was found in early (E) and late (A) transmitral filling velocity, velocity time integral E wave (VTIE) and A wave (VTIA), left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction (EF) and fractional shortening (FS). A significant difference was found in ratio E/A (P=0.04) and ratio VTIA/VTIE (P=0.05), although all obtained values were within the 95% confidence limit for the corresponding age. CONCLUSION: Our study tends to indicate the possibility of dysfunction of myocardial relaxation in glaucoma patients, which might be partially attributed to systemic vascular dysregulation.

Epidemiological study of nontraumatic phakic rhegmatogenous retinal detachment.

We studied the epidemiological characteristics of nontraumatic phakic rhegmatogenous retinal detachment (RRD) in a defined population of Split-Dalmatia County, Croatia. A total of 278 eyes of 272 patients developed RRD during an 11-year period, 1988-1998, with a population of 465,947. The annual incidence was 5.4 per 100,000 population. The mean age of patients was 58.3 years, and the sex distribution corresponded with that in the general population. There was insignificant preponderance of right eye involvement. Bilaterality was observed in 2.2%. The presence of myopia was diagnosed in 46.9% eyes.

Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer.

Various malignant tumors of the liver, especially liver angiosarcoma, have been described after occupational exposure to vinyl chloride monomer. We present the case records and pathologic findings of two plastic industry workers who had been exposed to high concentrations of vinyl chloride. These workers developed hepatic neoplasms, angiosarcoma, or hemangiopericytoma. We discuss the histogenesis of these tumors; the common vascular origin and the mutual transformation of these two tumors suggest that the hemangiopericytoma may also have developed during occupational exposure to high concentrations of vinyl chloride monomer.

Influence of betaxolol and timolol on the venous tone in glaucoma patients.

The aim of this study was the assessment of physiological venous reflexes in 40 glaucoma patients treated with topically applied timolol maleate 0.50% and betaxolol HCL 0.50%. They were divided into two groups of twenty each; one group being given timolol and the other betaxolol. The assessment of the venous tone was performed by testing venous reflexes. We found no statistically significant difference between timolol and betaxolol; however, when the influence of circulating catecholamines and the other vasoactive substances was excluded by suprasphygmatic insufflation of a pediatric cuff, a significant difference was found in the Valsalva's maneuver (125.5 +/- 8.1 vs 85.0 +/- 34.3 venoconstrictive units VCUs, p = 0.03). The IOP was significantly decreased in both treatment group, although the pressure reduction effect was more pronounced in the timolol group. Our study suggests that timolol and betaxolol have a slightly different mode of action on the venous side of circulation under topical medications. It is possible that the use of betaxolol topically may reduce a systemic venoconstriction.

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

Intraocular pressure and visual field defects.

During a five-year study period, therapeutic levels of intraocular pressure (IOP) and visual field defects were assessed in 108 patients with open-angle glaucoma. In a group of 53 glaucoma patients with non-progressive visual field changes (mean age 65.2 +/- 6.3 years), the IOP level was 15.8 +/- 2.6 mm Hg, whereas in a group of 58 patients with progressive visual field changes (mean age 68.7 +/- 8.3 years) the IOP level was 19.9 +/- 2.9 mm Hg. Study results suggested that preservation of the visual field in glaucoma patients requires therapeutic IOP levels of < 16 mm Hg.

The incidence of nontraumatic phakic rhegmatogenous retinal detachment in Split-Dalmatia County, Croatia.

We studied the incidence of nontraumatic phakic rhegmatogenous retinal detachment (RRD) in a defined population of Split-Dalmatia County, Croatia. In this clinic-based study, 272 of a population of 465,947 developed RRD during an 11-year period (1988-1998). The annual incidence was, therefore, 5.3 per 100,000 population. The highest risk for RRD was between the ages of 60 and 69 years.