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Inhibitory effect of clopidogrel, vapiprost and argatroban on the middle cerebral artery thrombosis in the rat.

This study investigated the roles of thromboxane A2 (TXA2), ADP and thrombin in middle cerebral artery (MCA) thrombosis in the rat. The rat MCA was occluded by a thrombus induced by the photochemical reaction of rose bengal by green light that causes endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of the photochemical reaction. Vapiprost, a specific TXA2-receptor antagonist; clopidogrel, which has the thienopyridine structure of ticlopidine and is a more potent inhibitor of ADP-induced platelet aggregation than ticlopidine; argatroban, a specific thrombin inhibitor; or heparin was administered intravenously before rose bengal injection. The MCA local blood flow was monitored by a laser Doppler flowmeter. The MCA was occluded by thrombus about 5 min after the initiation of the photochemical reaction. Vapiprost, clopidogrel and argatroban all significantly prolonged the time taken for the thrombotic occlusion of the MCA, but in this respect, heparin was ineffective. Our observations suggest that vapiprost and clopidogrel are useful antithrombotic agents against platelet and fibrin-rich thrombi. The effect of argatroban is attributable to inhibition of thrombin-induced platelet activation and fibrin generation. The thrombosis model described in this study is useful for understanding the mechanism(s) of thrombogenesis in the rat MCA and may be applied to other mammalian species.

Animals↗

[Study of 1,595 brucellosis cases in the Almeria province (1972-1998) based on epidemiological data from disease reporting].

OBJECTIVE: To know clinical, diagnostic, and treatment issues of brucellosis in the Almeria province. METHODS: Descriptive, epidemiological study from 1,595 disease report cards in the Almeria province during the 1972-1998 period. Issues concerning complications and treatment were reported in 890 cards (57.8%), symptoms, signs and hemograms in 565 (35.4%), and other diagnostic findings in all cards. The chi2 test was used to compare independent qualitative parameters for a 95% CI. RESULTS: In the early phase the most common symptom was asthenia (95.2%); sweating in the chronic stage (95.8%). The most commonly recorded sign was spleen enlargement (37.5%) and the most commonly reported complication was bone and joint involvement (22.8%). No changes in symptoms occurred over years. The hemogram revealed anemia in 30.3% of cases. Blood culture was positive for 91.2%. Regarding serological diagnosis, rose Bengal was positive for 99.2% of cases; the most common agglutination titer to Brucella or B. mellitensis was 1/640 (13.5%). The most commonly used therapy consisted of the association tetracycline plus streptomycin (42.4%). For 42.6% of cards, patients were transferred to hospital, particularly since 1984. CONCLUSIONS: Generally speaking, clinical data recorded in the reporting card regarding brucellosis disease reveal the clinical features of the disease, after a long surveillance period. Rose Bengal should be used as screening test for the diagnosis of this disease.

Brucellosis↗

Effect of taurocholate pretreatment on the biliary excretion of exogenous organic anions in rats.

The effect of pretreatment with taurocholate (1.12 mmol/kg per os twice daily for two days) on the biliary excretion of exogenous organic anions (rose bengal, bromcresol green, unconjugated and conjugated bromsulphthalein, eosine and amaranth) has been investigated in rats. Bromsulphthalein was excreted at a higher rate into the bile when its conjugation with glutathione was prevented by diethyl maleate (0.7 ml/kg i.p.). On the other hand, when conjugated bromsulphthalein was given intravenously, the taurocholate pretreatment failed to significantly enhance its biliary excretion rate. The changes found after taurocholate pretreatment in the biliary excretion of rose bengal and bromcresol green were similar to those observed during the excretion of unconjugated bromsulphthalein. However, in the biliary excretion of eosine and amaranth no increase was found following taurocholate pretreatment. The results indicate that taurocholate pretreatment does not exert a uniform stimulatory effect on the biliary excretion of exogenous organic anions.

Animals↗

Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune dacryoadenitis.

PURPOSE: To study the effects of induced autoimmune dacryoadenitis on lacrimal gland function, histopathology, and ocular surface disease in a rabbit model. METHODS: One lacrimal gland was surgically excised from each experimental rabbit, and epithelial cells were purified, cultured, irradiated, and then cocultured with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune dacryoadenitis was induced by injecting the autologous mixed cell reactions (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits with both lacrimal glands injected with nonstimulated PBLs were examined as controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy, Schirmer testing, tear break-up time measurement, and rose bengal examination. Sections of lacrimal glands removed at 8 weeks post-operation were immunostained using antibodies against rabbit class II major histocompatibility complex molecule (MHC-II), CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a ChromaVision image analysis system. RESULTS: During an 8-week period, a continuous decrease in tear production and stability, accompanied by a continuous increase in rose bengal staining, occurred in eyes in which AMCR-PBL had been injected into the ipsilateral lacrimal glands. Similar, though generally less severe, changes occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes by 8 weeks in these parameters were found in eyes in which the lacrimal glands had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes contralateral to normal eyes. Interstitial cells in normal lacrimal glands expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal mononuclear cell infiltrates were only found in lacrimal glands from animals with induced autoimmune dacryoadenitis. These cells were predominantly positive for CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase). MHC-II expression in interstitial and ductal epithelial cells was also significantly greater in these animals than in control animals. The mononuclear cell infiltrates were frequently found enveloping venules, some of which appeared to be high endothelial cell venules. The ductal epithelium also contained CD4 and CD8 immunopositivity, within the epithelium, at the lumenal surface, or surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be identified within the acinar lumens. CONCLUSIONS: Injection of activated PBLs (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune dacryoadenitis with immunopathologic features similar to those of Sjögren's syndrome. The lacrimal immunopathology is accompanied by typical clinical manifestations of dry eye syndrome. The persistent significant dry eye does not appear to result just from failure of the diseased gland but from a more general dysfunction of the surface secretory tissues.

Animals↗

Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group.

OBJECTIVE: To investigate the efficacy, safety, formulation tolerability, and optimal dosing of a novel cyclosporin A oil-in-water emulsion formulation for the treatment of moderate-to-severe dry eye disease. DESIGN: Randomized, multicenter, double-masked, parallel-group, dose-response controlled trial. PARTICIPANTS: Total enrollment: 162 patients; cyclosporin A groups: 129 patients; vehicle group: 33 patients. INTERVENTION: Patients instilled study medication (cyclosporin A ophthalmic emulsion 0.05%, 0.1%, 0.2%, or 0.4%, or vehicle) twice daily into both eyes for 12 weeks, followed by a 4-week posttreatment observation period. MAIN OUTCOME MEASURES EFFICACY: rose bengal staining, superficial punctate keratitis, Schirmer tear test, symptoms of ocular discomfort, and the Ocular Surface Disease Index (OSDI; a measure of symptom frequency and impact on vision-related functioning). SAFETY: biomicroscopy, cyclosporin A blood levels, conjunctival microbiology, intraocular pressure, visual acuity, and monitoring of adverse events. RESULTS: In a subset of 90 patients with moderate-to-severe keratoconjunctivitis sicca, the most significant improvements with cyclosporin A treatment were in rose bengal staining, superficial punctate keratitis, sandy or gritty feeling, dryness, and itching, with improvements persisting into the posttreatment period in some treatment groups. There was also a decrease in OSDI scores, indicating a decrease in the effect of ocular symptoms on patients' daily lives. There was no clear dose-response relationship, but cyclosporin A 0.1% produced the most consistent improvement in objective and subjective end points and cyclosporin A 0.05% gave the most consistent improvement in patient symptoms. The vehicle also performed well, perhaps because of its long residence time on the ocular surface. There were no significant adverse effects, no microbial overgrowth, and no increased risk of ocular infection in any treatment group. The highest cyclosporin A blood concentration detected was 0.16 ng/ml. All treatments were well tolerated by patients. CONCLUSIONS: Cyclosporin A ophthalmic emulsions, 0.05%, 0.1%, 0.2%, and 0.4%, were safe and well tolerated, significantly improved the ocular signs and symptoms of moderate-to-severe dry eye disease, and decreased the effect of the disease on vision-related functioning. Cyclosporin A 0.05% and 0.1% were deemed the most appropriate formulations for future clinical studies because no additional benefits were observed with the higher concentrations.

Adult↗

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

AIM: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). METHODS: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. RESULTS: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. CONCLUSION: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

Adult↗

A randomised, crossover, multicentre study to compare the performance of 0.1% (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of symptoms associated with dry eye syndrome.

AIMS: To assess the safety and performance of a 0.1% (w/v) solution of sodium hyaluronate (HA, Fermavisc, in the alleviation of symptoms of severe dry eye in comparison with a 1.4% (w/v) solution of polyvinyl alcohol. METHODS: A randomised, crossover, multicentre study carried out at eight centres in the UK. Eligible patients giving written informed consent were randomised to the order in which they would receive the two study products. Each treatment period lasted for 4 weeks, then the patient crossed over to the other study product. Symptoms of burning and grittiness were assessed by visual analogue scale (VAS) at each study visit and other objective clinical assessments of ocular structure and function were carried out at baseline and the end of each treatment period. RESULTS: Thirty-nine patients were entered into the study and 32 completed both treatment periods and were included in the statistical analyses. A significant improvement in the patients' VAS assessment of burning was seen after treatment with HA (P = 0.03, 95% Confidence Interval: -23.5 to -1.1). This treatment also resulted in a significantly lower rose bengal staining score (P = 0.04, 95% Confidence Interval: -1.62 to -0.05 for the right eye). CONCLUSION: The results show a significant clinical benefit in terms of relief of the symptom of burning when HA is applied topically to the eye three or four times per day or as required. HA also appears to have a protective effect on the corneal epithelium, as shown by a reduction in the level of staining of corneal epithelial cells by rose bengal. This study confirms that Fermavisc is a safe and effective product for use in the alleviation of symptoms of severe dry eye syndrome.

Adult↗

Effect of a Ca2+ entry blocker, nilvadipine, on hearing disturbances and equilibrium dysfunction caused by microcirculatory disorders of the rat inner ear.

We evaluated the effects of Ca2+ entry blockers, nilvadipine and flunarizine, on microcirculatory disorders of the inner ear and on blood flow in the inner ear of rats. Under sodium pentobarbital anesthesia, the middle ear was opened by a ventrolateral approach. A green light (wave length 540 nm) was applied to the cochlea or the vestibule to induce a hearing disturbance or equilibrium dysfunction as a result of inner ear microcirculatory disorders, while rose bengal solution was infused intravenously. In a hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute after the beginning of illumination. The sound stimulus was an 8 kHz sine wave 100 dB normal hearing level. The action potential was calculated 128 times. The action potential disappeared about 12 min after the beginning of illumination. In another model of equilibrium dysfunction, the photoillumination was applied for 40 min under the infusion of rose bengal. The behavior of rats was observed in the swimming test and nystagmus was recorded 24 h after the completion of photoillumination. In a separate experiment, blood flow in the inner ear was measured with a laser Doppler flowmeter under sodium pentobarbital anesthesia. In this study, both nilvadipine and flunarizine prolonged the time required for complete suppression of the action potential, prevented equilibrium dysfunction in the swimming test and reduced the occurrence of nystagmus. Flunarizine significantly increased inner ear blood flow and nilvadipine failed to decrease blood flow in the inner ear, despite a reduced systemic blood pressure. In conclusion, Ca2+ entry blockers may prevent microcirculatory disorders of the inner ear in rats.

Acoustic Stimulation↗

Antioxidant enzyme inhibitors enhance singlet oxygen-induced cell death in HL-60 cells.

Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. The protective role of antioxidant enzymes against singlet oxygen-induced oxidative damage in HL-60 cells was investigated in control and cells pre-treated with diethyldithiocarbamic acid, aminotriazole and oxlalomalate, specific inhibitors of superoxide dismutase, catalase and NADP+-dependent isocitrate dehydrogenase, respectively. Upon exposure to rose bengal (20 microM)/light (15 min), which generates singlet oxygen, to HL-60 cells, the viability was lower and the lipid peroxidation and oxidative DNA damage were higher in inhibitor-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species as well as the significant decrease in the intracellular GSH level in inhibitor-treated HL-60 cells exposed to singlet oxygen. Upon exposure to rose bengal (3 microM)/light (15 min), which induced apoptotic cell death, a clear inverse relationship was observed between the control and inhibitor-treated HL-60 cells in their susceptibility to apoptosis. These results suggest that antioxidant enzymes play an important role in cellular defense against singlet oxygen-induced cell death including necrosis and apoptosis.

Antioxidants↗

Impaired clearance of cholephilic anions in Rotor syndrome.

The behaviour of some cholephilic anions has been studied in three male patients (two of whom are brothers) affected with Rotor syndrome. The unconjugated bilirubin clearance was markedly reduced with impairment of the plasma-liver transfer constant rate (uptake defect). BSP retention at 45 min. was elevated without late rise of the anion. Transport maximum ("Tm") of BSP was slightly reduced; relative hepatic storage capacity of BSP ("S") was significantly impaired. Plasmatic retention of 131-I-Rose Bengal was increased with a diminished hepatic uptake of the compound. The hepatic excretion of IDA-derivatives was impaired, but less for parabutyl-IDA than for diethyl-IDA. It is concluded that in Rotor syndrome there exists an alteration of uptake and storage of several cholephilic organic anions: the alteration is common not only to substances that undergo intracellular conjugation--such as bilirubin and BSP--but also to substances that are not metabolized--such as Rose Bengal and IDA--derivatives. Finally the authors suggest that the Rotor syndrome and so--called "Hepatic storage disease" are the same condition.

Adult↗

Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study.

OBJECTIVES: To determine whether patients with primary Sjögren's syndrome (SS), diagnosed according to San Diego criteria, had improvement in their laboratory or clinical features during treatment with hydroxychloroquine (6-7 mg/kg/day) for at least two years. METHODS: The study population included 50 consecutive patients with primary SS who were diagnosed according to San Diego criteria, and in whom hydroxychloroquine was suggested as treatment. This group included 10 patients who were early dropouts (side effects or desire not to take antimalarial drugs) and 40 patients who received drugs for at least two years (range 24-48 months). In a subset of SS patients, values for ESR (westergren) and quantitative immunoglobulins were available for comparison. Improvement with therapy was defined as: (a) > or = 20% improvement in variables of tear flow (Schirmer's test I) or corneal integrity (rose Bengal): (b) > or = 20% salivary function (flow rate); and (c) improvement in at least two of the following measures: physicians assessment of global disease activity by > or = 20%, patient assessment of improvement in pain or fatigue by > or = 20%, and ESR improved by > or = 20 mm/hr. RESULTS: In a retrospective study of SS patients who completed the trial, a significant improvement was noted in ocular symptoms (pain and dryness) in patients (55 and 57%) and improved corneal integrity (rose Bengal straining) in 53% of patients. The Schirmer's test was improved by > or = 2 mm/5 minutes in 50% in patients. Improvement was noted in oral symptoms (pain and dryness) in patients (57 and 60%) and salivary flow rate was increased in 82% of patients. In a subset of SS patients evaluated, the ESR improved by > or = 20 mm/hr in 17/32 patients (53%) and quantitative IgG level by > or = 20% in 8/13 patients (61%). Physician global assessment of overall patient status and patient assessment of overall status indicated improvement in over 62% of patients. CONCLUSION: In a retrospective study of patients fulfilling San Diego Criteria for SS, we found: (a) sustained improvement of local symptoms (painful eyes, painful mouth) and improvement of systemic manifestations (arthralgias and myalgias) after treatment with hydroxychloroquine 6-7 mg/kg/day over mean three-year follow-up; (b) laboratory analysis showed a significant improvement in their ESR and their quantitative IgG levels; (c) no significant late toxicity was observed in this study cohort. A prospective study of hydroxychloroquine in patients fulfilling San Diego criteria for SS is indicated.

Adolescent↗

The Brucellin skin test as a tool to discriminate false positive serological reactions in bovine brucellosis.

Three experiments were performed in order to assess the diagnostic value of the Brucellin allergic skin test (AST) in a brucellosis false positive serological reactions (FPSR) context. First, 1259 cattle from 20 Brucella-free herds in a FPSR area were tested twice with AST to estimate its specificity. Secondly, AST and serological tests (complement fixation test [CFT], tube agglutination test, dithiothreitol-microagglutination test and ELISA) sensitivities were evaluated on 111 cattle positive to the Rose Bengal test (RBT) belonging to 15 Brucella-infected herds. Thirdly, AST was used in a field trial to discriminate FPSR from true brucellosis reactions. AST specificity in non-vaccinated cattle was very high (99.83%; confidence interval 95% [CI95%]: 99.67-99.96%). Skin thickening 72 h post-injection was significantly higher on vaccinated cattle (1.42 vs 0.15 mm). In this sub-population, AST specificity decreased significantly to 78% (CI95%: 68-87%). Individual sensitivity of AST relative to Rose Bengal test was 64% (CI95%: 54-72%), while all infected herds were AST positive (n = 15). When associated with CFT, it detected 95% (CI95%: 90-98%) of the infected cattle. These results were consistent with the field trial. In a FPSR context, AST was more specific than RBT or CFT. Therefore, this test could be used at herd level as a confirmation test, on cattle non vaccinated against brucellosis.

Animals↗

Decrease in corneal sensitivity and change in tear function in dry eye.

Our purpose was to investigate the relationship between insufficient tear secretion and decreased corneal sensitivity. We studied 59 patients with dry eye, 15 of whom had Sjögren's syndrome (SS), and 26 healthy subjects. Corneal sensitivity was measured by the esthesiometer of Cochet and Bonnet. Schirmer test with or without anesthesia, tear clearance rate, tear function index, and rose bengal and fluorescein staining were also evaluated. The mean corneal sensitivity of either dry-eye group (4.6 +/- 1.2 and 4.5 +/- 1.2 cm for non-SS and SS dry eye, respectively) was significantly lower than that of the control (5.8 +/- 0.4 cm, p < 0.001). Corneal sensitivity correlated significantly with the Schirmer values with anesthesia and the tear function index in the two dry-eye groups and the control (p < 0.05). There were significant relationships between corneal sensitivity and the rose bengal and fluorescein scores in the three groups (p < 0.05). Hyposecretion of tears in dry eye may lead to pathologic changes in corneal epithelium and a decline in corneal sensitivity. Prompt treatment of dry eye is essential to maintain a normal corneal protective mechanism.

Cornea↗

Secondary Sjögren's syndrome in rheumatoid arthritis.

One hundred and forty-three sequential, unselected patients with rheumatoid arthritis (RA) were prospectively evaluated for evidence of secondary Sjögren's syndrome (sSS). All of them had a labial salivary gland (LSG) biopsy, since a greater than or equal to 2+ score (Tarpley's classification) was considered mandatory for the diagnosis of sSS. One hundred eleven were completely investigated. The diagnosis of sSS was established when a patient with a positive LSG biopsy (greater than or equal to 2+ score) had keratoconjunctivitis sicca (KCS) (positive rose bengal test and/or the combination of subjective xerophthalmia and positive Schirmer's I) and/or xerostomia (subjective xerostomia and decreased parotid flow rate = [PFR]). Forty-four patients had an LSG biopsy score of greater than or equal to 2+, 28 a 1+ score and 39 a negative biopsy. Thirty-four of the 44 patients with positive biopsy had sSS, suggesting a 31% prevalence of sSS in RA. The 1+ score group represents a nonspecific category, resembling the negative biopsy group. Rose bengal test was very sensitive for sSS, whereas Schirmer's I and PFR were not. Parotid gland enlargement was unusual, and extraglandular manifestations, with the exception of diffuse interstitial lung disease, were relatively uncommon in all biopsy groups. No patient complained of xerophthalmia or xerostomia on his/her own. Anti-Ro (SSA) antibodies, detected in 23.5% of the patients with sSS, correlated well with positive LSG biopsy. Our study suggests that sSS in RA is common, benign and subclinical, requiring a positive lip biopsy and specific tests for its diagnosis.

Adult↗

Reactions of oxyphenbutazone with active oxygen species.

The ability of Oxyphenbutazone (a non-steroidal antiinflammatory drug) to react with singlet oxygen and superoxide anions, possible mediators of the damage to the lipids of the cell membranes during inflammation was studied. Oxyphenbutazone inhibited the reduction of nitroblue tetrazolium in aerobic riboflavin-photosensitized oxidation of methionine, but did not influence the cytochrome C-reduction by superoxide-generating system xanthine-xanthine oxidase. Oxyphenbutazone was photooxidized in the presence of Rose Bengal, the latter being a photosensitizer. The increase of the reaction rate of Oxyphenbutazone-oxidation in D2O as compared to H2O, as well as the inhibition of oxidation by singlet oxygen-quencher sodium azide confirmed the participation of singlet oxygen in this process. It was found that Oxyphenbutazone reacted with singlet oxygen, but did not react with superoxide anions. This was supported by the observed protection of erythrocyte membranes from the hemolytic action of the singlet oxygen-generating system Rose Bengal + light.

Animals↗

Correlation of tear lipid layer interference patterns with the diagnosis and severity of dry eye.

PURPOSE: To observe and classify tear film lipid layer interference patterns in normal volunteers and dry eye patients and to investigate the relation between the lipid layer interference patterns in the dry eyes and the results of other dry eye examinations. METHODS: Precorneal tear lipid layer interference patterns were observed at the central cornea in 25 eyes of 13 normal controls and 85 eyes of 48 dry eye patients. Observed patterns were classified in masked fashion by five physicians into five grades: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; and grade 5, corneal surface partially exposed. Other methods of dry eye examination were also performed, including the cotton thread test, the Schirmer I test and modified Schirmer I test, measurement of tear film breakup time, scoring of corneal fluorescein staining density (grades 0 to 3) and area (grades 0 to 3), and rose bengal staining (grades 0 to 9). RESULTS: In 92 (84%) of 110 eyes, four or more of the five physicians agreed in their grade classifications. Among the 92 eyes, normal control eyes were classified into grades 1 and 2 (10 and 12 eyes, respectively) and dry eyes were classified into grades 2, 3, 4, and 5 (22, 26, 10, and 12 eyes, respectively). There was a significant correlation between the grading and the results of other dry eye examination modalities, including fluorescein staining, rose bengal staining, and tear film breakup time. CONCLUSIONS: Tear lipid layer interference patterns are highly correlated with dry eye severity.

Adolescent↗

Radiopharmaceuticals for acutely damaged myocardium. II: Synthesis and evaluation of [203Hg] hydroxymercurifluoresceins.

Six [203Hg] hydroxymercurifluoresceins were prepared by two methods and compared with [3H] fluorescein, [131I] rose bengal, and [203Hg] mercuric nitrate, in a rat model for myocardial necrosis, to determine their specificities for damaged myocardium (DM). The nonhalogenated [203Hg] hydroxymercurifluorescein had the highest ratios of the series for DM/normal heart (51.5+/-13.5) and DM/blood (22.1+/-8.1). Halide substituents at the 2' or 4' positions of the fluorescein moiety decreased the tissue selectivity, and bis-hydroxymercuration had no significant effect. The six tracers studied had greater absolute uptake and better target-to-nontarget ratios than [3H] fluorescein, [131I] rose bengal, or [203Hg] mercuric nitrate, indicating a cooperative effect between the fluorescein and hydroxymercuri-moieties in the overall sequestration process in damaged tissues.

Animals↗

Botulinum toxin A treatment in patients suffering from blepharospasm and dry eye.

BACKGROUND: Many patients with essential blepharospasm also show dry eye signs and symptoms. Botulinum toxin A is an effective treatment for reducing spasms in these patients. In this investigation, the effect of botulinum toxin A injections on tear function and on the morphology of the ocular surface in patients suffering from blepharospasm in combination with a dry eye syndrome was investigated. METHODS: Botulinum toxin A injections were applied to 16 patients with blepharospasm. All patients complained of dry eye symptoms and had reduced tear break up time values. A subjective questionnaire and ocular examinations including tear break up time, Schirmer test without local anaesthesia, and rose bengal staining were evaluated before, 1 week, 1 month, and 3 months after injection. Impression cytology was performed before, 1 month, and 3 months after botulinum toxin A treatment. RESULTS: Although all patients were relieved of blepharospasm after botulinum toxin injections, only three noticed an improvement in dry eye symptoms. Eight patients noticed no difference and five complained of worsening. Tear break up time was found to be increased 1 week and 1 month after injections. Schirmer test measurements were reduced up to 3 months. Rose bengal staining slightly increased 1 week after injections. Impression cytology showed no definite change in conjunctival cell morphology 1 month and 3 months after botulinum toxin A injections. CONCLUSION: In the patients presented here suffering from blepharospasm and dry eye, botulinum toxin A injections were effective in relieving blepharospasm but were not successful in treating dry eye syndrome.

Adult↗