Smart contact lens: A promising therapeutic tool in aniridia.

OBJECTIVE: The perform pre-clinical testing using optical design tools to simulate the optical quality of a smart artificial iris platform encapsulated in a scleral contact lens. These tools allow us to generate aniridia eye models and evaluate different metrics of visual quality and retinal illumination based on the aperture of the artificial iris based on liquid crystals. METHOD: The OCT imaging technique was used to measure the geometry of the anterior segment in a patient with aniridia and, from these data, the eye model was generated with the Zemax optical design program and specific programs developed in Matlab. Ocular aberrations were calculated and the visual function of the anirida eye model was evaluated in three scenarios: (i) without optical correction, (ii) with correction with a commercial scleral contact lens, and (iii) with correction with an optical lens. Intelligent contact based on artificial iris. RESULTS: Optical quality in patients with aniridia is limited by the magnitude of high-order aberrations. Conventional scleral contact lens design accurately corrects for blur but is unable to compensate for high-order ocular aberrations, especially spherical aberrations. The artificial iris-based smart contact lens design enables virtually all high-order aberrations to be compensated with active control of the pupillary diameter (activation of liquid crystal cells based on ambient lighting). In addition to minimizing high-order aberrations, reducing the pupil size would increase the depth of focus. CONCLUSIONS: This article demonstrates by means of optical simulations the concept of an intelligent artificial iris platform encapsulated in a scleral contact lens and its possible application in patients with aniridia. Furthermore, it allows us to anticipate possible visual results in clinical trials with healthy patients (after application of mydriatic agents) and in patients with aniridia. The results demonstrate a better visual quality and a decrease in retinal illumination.

Smart contact lens: a promising therapeutic tool in aniridia. / Lente de contacto inteligente: una prometedora herramienta terapéutica en aniridia.

OBJECTIVE: To perform pre-clinical testing using optical design tools to simulate the optical quality of a smart artificial iris platform encapsulated in a scleral contact lens. These tools allow us to generate aniridia eye models and evaluate different metrics of visual quality and retinal illumination based on the aperture of the artificial iris based on liquid crystals. METHOD: The OCT imaging technique was used to measure the geometry of the anterior segment in a patient with aniridia and, from these data, the eye model was generated with the Zemax optical design program and specific programs developed in Matlab. Ocular aberrations were calculated and the visual function of the anirida eye model was evaluated in three scenarios: (i) without optical correction, (ii) with correction with a commercial scleral contact lens, and (iii) with correction with an optical lens. intelligent contact based on artificial iris. RESULTS: Optical quality in patients with aniridia is limited by the magnitude of high-order aberrations. Conventional scleral contact lens design accurately corrects for blur but is unable to compensate for high-order ocular aberrations, especially spherical aberrations. The artificial iris-based smart contact lens design enables virtually all high-order aberrations to be compensated with active control of the pupillary diameter (activation of liquid crystal cells based on ambient lighting). In addition to minimizing high-order aberrations, reducing the pupil size would increase the depth of focus. CONCLUSIONS: This article demonstrates by means of optical simulations the concept of an intelligent artificial iris platform encapsulated in a scleral contact lens and its possible application in patients with aniridia. Furthermore, it allows us to anticipate possible visual results in clinical trials with healthy patients (after application of mydriatic agents) and in patients with aniridia. The results demonstrate a better visual quality and a decrease in retinal illumination.

Evaluation of the Bio-Rad Dx CT/NG/MG® assay for simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium in urine.

We evaluated the performance of the Bio-Rad real-time Dx CT/NG/MG® assay for detection of C. trachomatis, N. gonorrhoeae and M. genitalium on a collection of 441 urine samples from sexually transmitted infections, or travellers consultations and from anonymous sperm donors that were previously analysed with the Abbott RealTime CT/NG assay. Samples positive for C. trachomatis or N. gonorrhoeae with the Abbott assay had all previously been confirmed with an in-house real-time PCR assay. Samples positive for M. genitalium with the Bio-Rad assay were subsequently analysed by an in-house real-time PCR. On a total of 441 urines, 104 samples were positive for C. trachomatis, 12 were positive for N. gonorrhoeae and seven were positive for M. genitalium. After retesting of discrepant results, the test results were completely concordant, resulting in a calculated sensitivity and specificity of the Bio-Rad assay of 98.1 % and 100 % for C. trachomatis and of 91.7 % and 100 % for N. gonorrhoeae. Results for M. genitalium with the Bio-Rad assay were also concordant with the results of an in house PCR. We also evaluated the performance of automated nucleic acid extractions of urine samples with the NucliSENS easyMAG (bioMérieux) compared to the manual DNA extraction prescribed by the insert of the kit. The easyMAG extraction gave lower Ct values, relieved inhibition and had a lower hands-on time.

Increased thirst and vasopressin secretion after myocardial infarction in rats.

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.

Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats.

1. Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2. In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3. In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4. Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5. We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo.

Evaluation of the Roche Neisseria gonorrhoeae 16S rRNA PCR for confirmation of AMPLICOR PCR-positive samples and comparison of its diagnostic performance according to storage conditions and preparation of endocervical specimens.

The AMPLICOR PCR was used to detect Neisseria gonorrhoeae in endocervical specimens. A 16S rRNA PCR performed on N. gonorrhoeae-positive samples showed sensitivities of 73.2, 64.3, and 94.4% for samples treated directly with AMPLICOR lysis buffer, samples suspended in 2-sucrose phosphate, and samples suspended in diluted phosphate-buffered saline, respectively.

Dynamics of (Cd,Zn)-metallothioneins in gills, liver and kidney of common carp Cyprinus carpio during cadmium exposure.

Cadmium concentrations, (Cd,Zn)-metallothionein (MT) concentrations, MT synthesis and the relative amounts of cadmium bound to (Cd,Zn)-MTs were determined in gills, liver and kidney of common carp Cyprinus carpio exposed to 0, 0.5 microM (0.06 mg.l(-1)), 2.5 microM (0.28 mg.l(-1)) and 7 microM (0.79 mg.l(-1)) Cd for up to 29 days. Cadmium accumulation was in the order kidney > liver > gills. Control levels of hepatic (Cd,Zn)-MT were four times higher compared to those of gills and kidney. No increases in (Cd,Zn)-MT concentrations were observed in liver during the exposure period. In comparison with control carp, (Cd,Zn)-MT concentrations increased up to 4.5 times in kidney and two times in gills. In both these organs, (Cd,Zn)-MT concentrations were linearly related with cadmium tissue levels and with the de novo synthesis of MTs. Hepatic cadmium was almost completely bound to (Cd,Zn)-MT, while percentages of non-MT-bound cadmium were at least 40% in gills and 25% in kidney. This corresponded with a total saturation of (Cd,Zn)-MT by cadmium in kidney and a saturation of approximately 50 and 60% in gills and liver, respectively. The final order of non-MT-bound cadmium was kidney > gills > liver. Our results indicate that cadmium exposure causes toxic effects, which cannot be correlated with the accumulated levels of the metal in tissues. Although cadmium clearly leads to the de novo synthesis of MT and higher (Cd,Zn)-MT concentrations, the role of this protein in the detoxification process is clearly organ-specific and its synthesis does not keep track with cadmium accumulation.

Stress responses and changes in protein metabolism in carp Cyprinus carpio during cadmium exposure.

Stress responses and changes in protein metabolism were studied in common carp Cyprinus carpio exposed to 0, 0.8, 4, and 20 microM cadmium (Cd) over a 29-day period. Blood and other tissue samples were taken after 4 and 29 days of exposure. The highest Cd concentration proved to be lethal to the fish, resulting in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma glucose, plasma lactate, and tissue total protein contents were not significantly altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd, Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)-MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in liver. The concentrations of free amino acids and the activities of proteases were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20 microM Cd, and in gills and kidney at Day 29 in carp exposed to 4 microM Cd. The observed increases in the activities of aspartate aminotransferase and alanine aminotransferase suggest that the observed proteolysis is intended to increase the role of proteins in the energy production during Cd stress. However, this increased activity of both aminotransferases was not found in gills during exposure to the lethal Cd concentration, indicating that Cd may also cause an inhibitory effect on the activity of these enzymes above a certain level.

Cadmium-binding to transferrin in the plasma of the common carp Cyprinus carpio.

In this study, it was investigated by autoradiography with radioactive cadmium after Western blotting of two-dimensional electrophoresis gels, to which proteins cadmium is mainly bound in plasma of common carp Cyprinus carpio. The obtained results demonstrate that in carp plasma, cadmium is primarily bound to two high molecular weight proteins. Relative small amounts are bound to a protein with M(r) approximately 60000. The other metal-binding protein, with M(r) approximately 70000 and pI approximately 6.7 was identified as transferrin. The conditional equilibrium constants for the binding of cadmium ions to the two metal-binding sites of this protein were calculated as logK(1)=5.40+/-0.12 and logK(2)=4.66+/-0.21, which are comparable to those of human transferrin under the same experimental conditions. Transport of cadmium in plasma of carp was found to be different from that of brown trout Salmo trutta and man, where cadmium is mainly bound to albumin and transferrin. The prominent binding of cadmium to transferrin can be explained by the absence or at least the very low concentrations in which albumin is present in carp plasma.

Classification of medicines according to their influence on driving ability.

Within the scope of an information campaign of the Belgian Institute for Road Safety an attempt was made to classify 179 medicinal drugs from 9 therapeutic groups, listed in the Belgian "Commented Repertory of Drugs--1997", according to their effect on driving performance. The categorisation was based on literature data from about 500 references and used the system proposed by Wolschrijn et al [1]: 7 classes ranging from no effect (I) over minor and moderate (II.1,II.2) to severe effects (III), completed with the respective* categories (I*,II*,III*) for presumed classes with insufficient scientific data. Forty-two drugs (24%) were considered having severe effects (III/III*). Only 28/179 molecules (16%) were classed in I/I*: no hypnotics-sedatives (33), anticonvulsants (10), antidepressants (25), neuroleptics (29), nor narcotic analgesics and antitussives (18) were listed in this no-effect category, while for 7/24 antihistamines (5/20 H1 and 2/4 H2), 12/20 beta blockers and 9/10 central stimulants the effect was considered negligible. Antidiabetics were not classified, as the danger lies in the risk of hypoglycemia due to inadequate use. The classification of the molecules proved to be problematic due to the lack of study data (42% of molecules in presumed categories) and the diversity in the study protocols. The effect on driving ability is dose-dependent and time-related, which makes the use of a single category inadequate; the effect further depends on co-ingestion of other medicines or alcohol, the development of tolerance and the condition of the subject. Physicians and pharmacists can use the proposed categorisation as a scientific base for guiding their patients, but should take into account the factors involved for each patient when estimating the driving ability.

Parinaud's syndrome in a patient with multifocal glioma.

We describe the clinical and neuroradiological findings in a 63-year-old man with Parinaud's syndrome. Magnetic resonance (MR) imaging showed a mass lesion within the quadrigeminal plate. Additional MR findings included a right frontoparietal subcortical lesion as well as periventricular white matter edema due to acute deterioration of hydrocephalus. On MR, the diagnosis of multifocal glioma was proposed. Neuropathological examination after resection of the supratentorial lesion revealed an oligodendroglioma, grade II.

Intrasellar bony spine, a possible cause of hypopituitarism.

A 39-year-old male patient with long-standing pituitary deficiency is reported. The onset of hypopituitarism was probably at about the age of 12 years, but diagnosis was not made until 6 years later. Since then he has received substitutive hormonal treatment and was referred with complaints suggestive of growth hormone deficiency. Retrospective study of a skull radiography performed at the age of 18 years revealed a calcified lesion in the sellar region. Additional radiological examinations showed the presence of a 9-mm intrasellar bony spine. Magnetic resonance examination showed a ventrally extending arrow-shaped bone deformation in continuity with the dorsum sellae, consisting of a hyperintense structure comparable with the intensity of the bone marrow of the dorsum and clivus. Computed tomography scanning confirmed in detail the morphology of the bony spine. This deformity probably represents the non-regressed cephalic segment of the notochord. Only in four reports has the existence of this congenital abnormality been described, but this is the first one in which hypopituitarism can be regarded as a complication of the intrasellar spine.

Surgical treatment of myogenic blepharoptosis.

We describe the surgical approach of two patients with myogenic blepharoptosis. The ptosis is caused by a glycogenosis type II (Pompe disease) in the first case and is due to a juvenile, chronic progressive external ophthalmoplegia (Kearns-Sayre syndrome) in the second case. The first patient presented a unilateral ptosis. The ptosis in the second patient was bilateral and manifest. The eyelids could only be opened manually. A resection of the palpebral levator muscle was carried out under local anesthesia. The choice of the technique will be explained. The amount of levator resection was calculated considering the residual eyelid motility and Bell's phenomenon. Electronmicroscopy of the resected levator muscle will be discussed.

Emergence of Haemophilus ducreyi resistance to trimethoprim-sulfamethoxazole in Rwanda.

The in vitro susceptibilities of 112 clinical isolates of Haemophilus ducreyi to six antimicrobial agents were determined. These isolates were obtained in Kigali, Rwanda, during three studies on genital ulcer disease performed in 1986 (18 isolates), 1988 (23 isolates), and 1991 (71 isolates). All H. ducreyi isolates were susceptible to azithromycin, ceftriaxone, ciprofloxacin, and erythromycin; all isolates obtained in 1986 were also susceptible to trimethoprim and to the combination trimethoprim-sulfamethoxazole. In contrast, 39 and 9% of the isolates obtained in 1988 and 59 and 48% of the isolates obtained in 1991 were resistant to trimethoprim (MIC, > or = 4.0 mg/liter) and trimethoprim-sulfamethoxazole (MIC, < or = 4.0/76 mg/liter), respectively. These data indicate that trimethoprim-sulfamethoxazole can no longer be recommended for use in the treatment of chancroid in Rwanda, and possibly elsewhere in Africa.

Comparison of E test with agar dilution for antimicrobial susceptibility testing of Neisseria gonorrhoeae.

A collection of 150 Neisseria gonorrhoeae isolates from Africa, where various resistance mechanisms among N. gonorrhoeae isolates are common, was used to the compare E test (AB Biodisk, Solna, Sweden) with agar dilution susceptibility testing. MICs obtained by the E test agreed within 1 log2 concentration by the agar dilution method for 97.5, 97.3, 96.6, 94, and 84.7% of the tested isolates for penicillin, ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole, respectively. No significant difference in susceptibility categorization was observed between either method. The E test is an attractive alternative to the agar dilution technique and is a more appropriate method for N. gonorrhoeae susceptibility testing in developing countries.

Surgical technique for patients with the apractic type of essential blepharospasm: case report.

A frontalis suspension was carried out in a patient with an essential type of blepharospasm, characterized by difficulties in initiating the act of lid elevation, often referred to as the apractic form of blepharospasm or, as J. Elston proposed, the pretarsal blepharospasm. The patient tries to open the eyes by using the frontalis muscle or by manual traction. It is known than in this form of blepharospasm, insufficient results are seen after botulinum toxin infection. Proper examination of the skin crease of the upper eyelid and of the eyelid gives an idea of the insertion of the levator aponeurosis and of the levator muscle function. A desinsertion, due to frequent manual traction, may be found. In this case, reinsertion of the aponeurosis may relieve the symptoms. If no desinsertion is present a frontalis suspension, similar to those used in ptosis surgery, may give good results.

The time course of a sixth nerve paresis following epidural anesthesia.

An isolated sixth nerve palsy is seldom seen following epidural anesthesia. An unintentional puncture through the dura may cause a leak of cerebrospinal fluid resulting in a shift of the cerebral content. This may cause a stretching of the sixth cranial nerve giving an abduction palsy. The palsy is benign and resolves completely within two months. The time course of a case will be described.

Levator aponeurosis dehiscence in a patient treated with botulinum toxin for blepharospasms and eyelid apraxia.

A 63 years old woman presented with bilateral blepharospasms and eyelid apraxia which was treated with Botulinum toxin injections. A post-treatment ptosis was seen with preserved levator function. It was then suggested that manual eyelid traction could have caused aponeurotic dehiscence of the levator muscles. Surgical exploration confirmed this diagnosis. One must be aware that eyelid apraxia can mask an aponeurotic dehiscence of the levator muscle induced by chronic manual traction exerted on the apractic eyelids.