Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats.

Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

Histopathological Changes in the Kidney following Congestive Heart Failure by Volume Overload in Rats.

BACKGROUND: This study investigated histopathological changes and apoptotic factors that may be involved in the renal damage caused by congestive heart failure in a rat model of infrarenal aortocaval fistula (ACF). METHODS: Heart failure was induced using a modified approach of ACF in male Wistar rats. Sham-operated controls and ACF rats were characterized by their morphometric and hemodynamic parameters and investigated for their histopathological, ultrastructural, and apoptotic factor changes in the kidney. RESULTS: ACF-induced heart failure is associated with histopathological signs of congestion and glomerular and tubular atrophy, as well as nuclear and cellular degeneration in the kidney. In parallel, overexpression of proapoptotic Bax protein, release of cytochrome C from the outer mitochondrial membrane into cell cytoplasm, and nuclear transfer of activated caspase 3 indicate apoptotic events. This was confirmed by electron microscopic findings of apoptotic signs in the kidney such as swollen mitochondria and degenerated nuclei in renal tubular cells. CONCLUSIONS: This study provides morphological evidence of renal injury during heart failure which may be due to caspase-mediated apoptosis via overexpression of proapoptotic Bax protein, subsequent mitochondrial cytochrome C release, and final nuclear transfer of activated caspase 3, supporting the notion of a cardiorenal syndrome.

Online removal of eye movement and blink EEG artifacts using a high-speed eye tracker.

A novel approach is presented for using an eye tracker-based reference instead of EOG for methods that require an EOG reference to remove ocular artifacts (OA) from EEG. It uses a high-speed eye tracker and a new online algorithm for extracting the time course of a blink from eye tracker images to remove both eye movement and blink artifacts. It eliminates the need for EOG electrodes attached to the face, which is critical for practical daily applications. The ability of two adaptive filters (RLS and H^ ) to remove OA is measured using: 1) EOG; 2) frontal EEG only (fEEG); and 3) the eye tracker with frontal EEG (ET + fEEG) as reference inputs. The results are compared for different eye movements and blinks of varying amplitudes at electrodes across the scalp. Both the RLS and H^ methods were shown to benefit from using the proposed eye tracker-based reference (ET + fEEG) instead of either an EOG reference or a reference based on frontal EEG alone.

Viscocanalostomy versus trabeculotomy ab externo in primary congenital glaucoma: 1-year follow-up of a prospective controlled pilot study.

AIM: To study the effectiveness of viscocanalostomy in patients with primary congenital glaucoma of the isolated trabecular dysgenesis category and compare it with trabeculotomy ab externo. METHODS: Eight patients with bilateral primary congenital glaucoma were enrolled in the study. After establishing the diagnosis, the more severely affected eye was randomly selected to undergo either trabeculotomy ab externo or viscocanalostomy, whereas the second eye underwent the other surgery 2 weeks after the first. The patients were examined on day 1, week 1, week 4 and thereafter every 4 weeks. Intraocular pressure (IOP) and corneal diameter measurements were obtained at week 1, month 6 and at the last reported follow-up. The paired-sample's Student's t test was applied for statistical analysis. RESULTS: The mean (standard deviation (SD)) follow-up period was 12.5 (1.86) months. Preoperative IOP of eyes undergoing trabeculotomy (34.0 (2.6) mm Hg) and that of eyes undergoing viscocanalostomy (32.3 (4.1) mm Hg) showed no significant difference (p>0.1). A drop in IOP was noted in both groups at week 1, month 6 and at the last follow-up visit (p<0.001). Similarly, a decrease in the postoperative vertical and horizontal corneal diameters was noted in the two study groups. CONCLUSION: Viscocanalostomy proved to be as effective as trabeculotomy ab externo in lowering IOP. Moreover, it is likely to be a good surgical alternative with a higher long-term success rate in eyes with more aggressive disease.

Diode laser transcleral cyclophotocoagulation for refractory glaucoma: a 1 year follow-up of patients treated using an aggressive protocol.

PURPOSE: To prospectively evaluate the intraocular pressure (IOP) lowering ability, retreatment rate, and complications of transcleral Diode laser cyclophotocoagulation using a higher power setting than what is generally recommended. PATIENTS AND METHODS: A total of 36 eyes of thirty six patients with refractory glaucoma, and who fitted our inclusion criteria underwent Diode cyclophotocoagulation. The laser power was set at 2250 mW, with a duration of 2000 ms, and a total number of 28 shots for the first treatment and 20 shots for any consequent one. The patients were followed up for 1 year with the following outcomes being analysed: IOP, visual acuity, change in the number of medications, and complications. RESULTS: The mean IOP decrease was 53% (P < 0.05), and 72.2% of the patients maintained an IOP < or =21 mmHg for the whole duration of the study The number of medications necessary to control the pressure, significantly dropped from 2.8 to 0.89 (P < 0.05), and 25% of the patients needed the treatment to be repeated only once. In all, 33% of the patients improved their visual acuity after the treatment, while 22% worsened, and the rest stayed the same. The most common treatment complications were conjunctival injection and corneal oedema, and these were both transient and reversible. CONCLUSION: The use of the higher power setting of 2250 mW, resulted in a sustained lower IOP, less use of medications, less need for retreatment, relative preservation of visual acuity, and only reversible complications.

Ocular toxicity in low-dose tamoxifen: a prospective study.

PURPOSE: To look at the incidence, symptomatology, course and reversibility of low-dose tamoxifen ocular toxicity. METHODS: Sixty-five women with breast cancer, on tamoxifen oral therapy (20 mg/day), and a totally normal eye examination, were prospectively followed up. A full ophthalmic evaluation was done every 6 months, for a median of 30 months (range 4-79 months). Any sign of toxicity in the cornea, lens, retina or optic nerve was looked for, whether associated with a change in visual acuity or not. RESULTS: Ocular toxicity was documented in 8 patients, giving an incidence of 12%. Seven patients had keratopathy in the form of subepithelial deposits, whorls and linear opacities. Three of these patients had a concurrent symptomatic bilateral pigmentary retinopathy that warranted discontinuation of therapy. One patient developed bilateral optic neuritis that left her with optic nerve pallor and a decrease in vision. The patients who had the toxicity had a significantly higher tamoxifen cumulative dose (p = 0.03), and were longer on treatment (p = 0.04), than the non-affected ones. The keratopathy changes were reversible upon discontinuation of the drug. CONCLUSION: Prompt reporting of symptoms and yearly ophthalmic examinations are mandatory in patients on tamoxifen to detect toxic effects while these are still reversible.

Effect of surgery on visual field progression in normal-tension glaucoma.

PURPOSE: The effect of intraocular pressure-lowering surgery on the rate of visual field progression in normal-tension glaucoma (NTG) was studied. METHODS: Seventeen patients with NTG who underwent trabeculectomy in one eye for worsening visual field loss were included in the first part of the study. All patients had Humphrey 24-2 visual fields at the rate of 2-3 fields per year. Pointwise linear regression analysis of the visual field data was done separately for the preoperative and postoperative periods. This was performed for both operated and fellow eyes. The mean slope (MS), which indicates rate of visual field progression, was calculated. Change in MS was correlated with change in intraocular pressure (IOP). For the second part of the study, 11 patients who had a minimum of 4 visual fields and 18 months of follow-up before surgery were identified. Using the preoperative fields, the rate of sensitivity loss for each visual field location in the operated eye was ascertained for every patient. This rate of loss was extrapolated to generate the expected visual fields, assuming an unchanged rate of progression. The mean sensitivity of the expected visual field was compared with that of the actual field at the last follow-up. RESULTS: The MS in the operated eyes improved from -2.97 +/- 3.21 (mean +/- SD) in the preoperative period to 0.53 +/- 3.83 (P < 0.005; Student's t test) postoperatively. In the fellow eyes the MS changed from -1.78 +/- 2.55 to -1.43 +/- 3.01 (P = 0.754). There was a weak correlation between change in MS and percentage IOP decrease (correlation coefficient 0.39). The difference in mean sensitivity between the expected and actual visual fields was -3.72 dB (P = 0.002), and was better in the actual field. CONCLUSIONS: In this study, surgical lowering of IOP resulted in a slower rate of visual field loss in the operated eye.

A family with a syndrome of ectopia lentis, spontaneous filtering blebs, and craniofacial dysmorphism.

Six members of a family presented with a syndrome of mild facial dysmorphism, subluxation of the crystalline lenses, variable degrees of angle closure by iridocorneal adhesions, and patchy areas of iris atrophy. Three nonoperated eyes of two patients had spontaneous filtering blebs that presented as avascular cystic elevations of the superior conjunctiva. Systemic workup of all patients was negative for evidence of diseases known to be associated with dislocated lenses. The pedigree is most compatible with autosomal recessive inheritance with pseudodominance.

Conjunctival changes after subconjunctival lignocaine.

Subconjunctival injection of 2% lignocaine at the 12 o'clock position was used as the local anaesthetic in 19 eyes undergoing a primary trabeculectomy for open angle glaucoma. The appearance of the bleb and mean post-operative intraocular pressure (IOP) were compared with those in 29 eyes with the same diagnosis undergoing trabeculectomy under general anaesthesia by the same surgeons over the same time period. The two groups of eyes were similar with regard to treatment with beta blockers (p > 0.1), miotics (p > 0.25), sympathomimetics (p > 0.25), carbonic anhydrase inhibitors (p > 0.5), or no treatment (p > 0.25). Seventy-seven per cent of the local anaesthetic group and 25% of the general anaesthetic group developed avascular, thin-walled drainage blebs (p < 0.001). The mean post-operative IOP was significantly lower in the group receiving local anaesthetic (p < 0.001). The reasons for and significance of these observations are discussed, and the merits and disadvantages of thin-walled blebs are evaluated.

Advanced uncontrolled glaucoma. Nd:YAG cyclophotocoagulation or tube surgery.

Forty-five patients with advanced uncontrolled glaucoma who had had noncontact neodymium:YAG (Nd:YAG) cyclophotocoagulation were matched and compared with 45 patients who underwent tube implantation surgery. The matching was based on selected criteria, including diagnosis, number of previous operations on the index eye, number of previous glaucoma operations, aphakia, vitrectomy, and age. The drop in intraocular pressure (IOP) was statistically significant in each of the 2 groups at 1, 4, 6, and 12 months of follow-up (P less than 0.001). The tube patients needed fewer antiglaucoma medications at 1 year (P less than 0.025) and more surgical intervention for IOP control, although this was not statistically significant (P greater than 0.1). Laser treatment was repeated in 49% of cases, and age younger than 40 years was identified as a risk factor for poor response to this mode of therapy. The effect on visual acuity and the expected complications also are discussed.

Regression analysis of visual field progression in low tension glaucoma.

Eighty four patients (168 eyes) with low tension glaucoma were retrospectively reviewed (mean follow-up was 28 months). The mean age was 66 years, and 69% were females. Regression analysis of their automated Humphrey fields (a mean of eight fields per eye) showed progression in 50% of patients and in 37% of eyes. There was no statistically significant difference between patients with progression and non-progression with respect to age (p less than 0.05) or intraocular pressure (p less than 0.5). Visual field defects were located most frequently in the superior hemifield in both groups of patients. A considerable proportion of patients had advanced field loss at the time of diagnosis.