[Successful treatment of resistant Fusarium solani keratitis with liposomal amphotericin B]. / Efficacité de l'amphotéricine B liposomale dans le traitement d'une kératite àFusarium solani résistante.

INTRODUCTION: The prognosis for Fusarium keratitis is poor. Effective drugs to treat this infection are therefore needed. CASE REPORT: A patient presented Fusarium solani keratitis. The infection regressed with topical amphotericin B and intravenous voriconazole. Topical steroids were introduced. There was reactivation and extension of the infection, invading the anterior chamber. Steroids were discontinued and the antifungal treatment was restarted but there was continued deterioration. Recovery was achieved without surgery, with topical voriconazole, topical liposomal amphotericin B, topical natamycin, intravenous liposomal amphotericin B, and intravenous voriconazole. CONCLUSION: Combined orally and topically administered voriconazole is a promising therapy when the minimum inhibitory concentration is approximately 2 microg/ml. Liposomal amphotericin B seems to be the most effective drug for the different infection stages. Posaconazole is a useful alternative but further investigations must be pursued.

[Corneal tattooing. A series of 14 case studies]. / De l'usage du tatouage cornéen. A propos de 14 cas.

AIMS: Evaluate the efficacy of a little-used surgical method: corneal tattooing, using a dermograph to hide unsightly corneal scars on nonfunctional eyes. PATIENTS AND METHODS: Retrospective study of 14 eyes of 13 patients treated by tattooing the corneal surface, by directly introducing the pigments into the corneal stroma using a dermograph. The effectiveness of tattooing was evaluated by pigmentation homogeneity and patient satisfaction. Tolerance was evaluated by the scarring at the 7th day and ocular inflammation. The average follow-up was 18 months. RESULTS: Fourteen eyes presented an unaesthetic, neovascularized major corneal edema (79% traumatism). In 12 eyes, the treatment was homogeneous with a very satisfactory aesthetic result for the patient. One eye presented minor complications of pigmentary migration. One eye presented a corneal perforation 40 days after the procedure on a very pathological cornea. CONCLUSION: Corneal tattooing using a dermograph is a little-used technique since changes in corneal transplantation indications but is also a simple and inexpensive alternative for corneal scar treatment on nonfunctional eyes.

[Visual outcome in keratoconus patients 1 and 2 years after penetrating keratoplasty]. / Acuité visuelle un et deux ans après kératoplastie transfixiante pour kératocône.

PURPOSE: To quantify the visual outcome obtained in patients operated on for penetrating keratoplasty for keratoconus (KC) after 1 and 2 years. PATIENTS: and methods: The files from consecutive keratoconus patients operated on for PKP after more than 2 years of follow-up were retrospectively studied. The demographic charts, the KC stage, and the surgical features were noted. The best corrected visual acuities (BSCVA) were analyzed at the initial examination and after 1 and 2 years of follow-up. RESULTS: One hundred and two eyes from 98 patients were analyzed, including 83 grade 4 (81%) and 19 grade 3 (18%) cases of KC. The mean preoperative BSCVA was 0.08 on the decimal chart, which increased to 0.5 and 0.6 1 and 2 years after penetrating keratoplasty (p<0.001, respectively). The mean keratometric astigmatism was 3.80+/-2.9 D and 3.94+/-2.3 D for the grade 3 and 4 KC, respectively, after 1 year and 2.52+/-1.9 D and 3.34+/-2.2 D after 2 years (NS). At this time point, 81% of the eyes had less than 5 D astigmatism. CONCLUSION: One and 2 years after penetrating keratoplasty, a mean BSCVA of 0.5 and 0.6 could reasonably be expected in keratoconus patients and three-quarters of patients can be expected to see better than 0.5 after 2 years.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes.

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8-12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50microm, 400mW, 0.05s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I (n=12), photocoagulation controls, did not receive any intravitreous injection. Group II (n=12), received an intravitreous injection of 1microl of balanced salt solution (BSS). Group III (n=12), received an intravitreous injection of 1microl containing 15microg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV (n=10) received 1.5, 3, 7.5, 15, or 30microg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15microg/mul of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.

[Inadvertent intravitreal lidocaine injection following subcutaneous palpebral anesthesia: retinal toxicity of lidocaine?]. / Injection intravitréenne accidentelle de lidocaïne au cours d'une anesthésie palpébrale: toxicité rétinienne de la lidocaïne?

INTRODUCTION: We report an atypical case of scleral perforation due to an inadvertent intravitreal lidocaine injection following palpebral anesthesia. We discuss the management of this rare complication and focus on the transient lidocaine toxicity on human retina. OBSERVATION: A 29-year-old man presented with unilateral decreased vision during a lower right palpebral anesthetic injection for a chalazion removal procedure. The patient's vision was light perception. Examination revealed intraocular pressure at 55 mmHg, a wound of the posterior crystalloid, an intraocular gas bubble, and a central retinal artery spasm. On ERG, the b wave was decreased. The central retinal artery spasm resolved with prompt reduction of hypertony. Twenty-four hours later, the vision was 6/10 and the ERG showed an increased b wave activity. No clinical retinal toxicity of lidocaine was observed. Only a subcapsular cataract was observed, which had caused the loss of vision. CONCLUSION: This case confirms that lidocaine is well tolerated by the retina and reminds us that superficial palpebral anesthetic injection should be done with great caution.

Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-alpha soluble receptor in uveitis.

Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.

The effects of acute and subchronic treatment with fluoxetine and citalopram on stimulus control by DOM.

Previous reports from our laboratory have provided evidence that acute, i.e., concurrent, treatment with selective serotonin reuptake inhibitors (SSRIs) augments the stimulus effects of indoleamine and phenethylamine hallucinogens in the rat. In the present investigation, the acute effects of fluoxetine and citalopram on stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM) were compared with those following subchronic, i.e., 10-day treatment with the SSRIs. Stimulus control was established using DOM (0.56 mg/kg; 75-min pretreatment time) in a group of 11 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. The effects of a range of doses of DOM when given alone were compared with those following both acute and subchronic pretreatment with fluoxetine and citalopram in combination with DOM. It was found that acute administration of fluoxetine and citalopram potentiated the stimulus effects of DOM. Furthermore, it was observed that the degree of potentiation was not diminished by treatment with either fluoxetine or citalopram for a period of 10 days. It is concluded that whatever adaptive changes may take place in response to a 10-day period of treatment with either citalopram or fluoxetine, these adaptations are independent of the mechanisms responsible for the potentiation of the stimulus effects of DOM by the SSRIs.

Potentiation of DOM-induced stimulus control by fluoxetine and citalopram: role of pharmacokinetics.

The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and the selective serotonin reuptake inhibitor [SSRI] citalopram in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with citalopram at a dose of 1.0 mg/kg shifted the DOM dose response relationship to the left. Unlike previously tested SSRI's, the enhancement of DOM-induced stimulus control occurred in the absence of significant partial substitution by citalopram. DOM brain levels were measured using a GC-MS method both in the presence and absence of citalopram and fluoxetine in order to evaluate the pharmacokinetic contribution to the observed behavioral effect. The data indicated that fluoxetine but not citalopram significantly increased DOM brain levels. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by the acute administration of citalopram and this effect is not mediated by additivity or pharmacokinetic mechanisms.

Neural transplants. effects On startle responses in neonatally MSG-treated rats.

Neonatal monosodium glutamate (MSG) treatment has been associated with dysfunctions in stress responses. Therefore, the present study aimed at examining the acoustic startle response (ASR) in MSG-treated rats and the effects of fetal neural transplantation. Male and female rats were given MSG (4 mg/g) or saline on alternate days from days 2-10 after birth. To determine whether fetal transplants could reverse behavioral impairments observed in MSG-treated rats, at 12 days of age MSG-treated rats received either arcuate nucleus (AN), cortical fetal grafts, or sham surgery into the third ventricle. ASR amplitude was measured at 35-40 days of age, and again in adulthood. MSG produced the expected decrease in the density of hypothalamic neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the AN area. Corticotropin-releasing factor (CRF) neurons/fibers were not affected by MSG. Pituitary atrophy was observed in all MSG rats. We report a permanent increase in the amplitude and reduction in short-term habituation of ASR in all MSG-treated rats. No effect was observed on long-term habituation in male rats. Cortical, but not AN tissue significantly reduced the magnitude of ASR in MSG animals. The results are discussed in terms of the central pathways mediating ASR, in particular hypothalamo-amygdala connections. It is considered that nonspecific factors mediate recovery produced by cortical tissue grafts, as observed in other models of neural transplantation.

Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia.

The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders.

Long-term (10 years) prognostic value of a normal thallium-201 myocardial exercise scintigraphy in patients with coronary artery disease documented by angiography.

In order to assess the prognostic significance of normal exercise thallium-210 myocardial scintigraphy in patients with documented coronary artery disease, we studied the incidence of cardiac death and non-fatal myocardial infarction in 69 symptomatic patients without prior Q wave myocardial infarction, who demonstrated one or more significant coronary lesions (stenosis > or = 70%) on an angiogram performed within 3 months of scintigraphy (Group 1). These patients were compared to a second group of 136 patients with an abnormal exercise scintigram, defined by the presence of reversible defect(s) and angiographically proven coronary artery disease (Group 2), and to a third group of 102 patients with normal exercise scintigraphy without significant coronary lesions (stenosis < or = 30%) or with normal coronary angiography (Group 3). In contrast to coronary lesions observed in Group 2, patients in Group 1 presented more frequently with single-vessel disease (83% vs 35%, P < 0.0001) and with more distal lesions (55% vs 23%, P < 0.0001). Over a mean follow-up period of 8.6 years, one fatal and eight non-fatal cases of myocardial infarction were observed in Group 1. The majority of patients in Group 1 were treated medically: only 24 (35%) underwent myocardial revascularization, usually by coronary angioplasty. There was no significant difference in the incidence of combined major cardiac events (cardiac death, non-fatal myocardial infarction) in patients with normal exercise scintigraphy, with or without documented coronary artery disease (Groups 1 and 3), while the incidence was higher in Group 2. However, while the mortality remained very low in Group 1, the incidence of non-fatal myocardial infarction was not different from that of Group 2, where most patients underwent revascularization procedures. In conclusion, patients with coronary artery disease and a normal exercise thallium-201 myocardial scintigram usually have mild coronary lesions (single-vessel disease, distal location) and good long-term prognosis, with a low incidence of cardiac death.

Sexual reinforcement in the female rat.

Sexual reinforcement in the female rat was studied in a preparation that allowed continuous operant responding for access to a male rat leading to intromission. Experiment 1 used a high operant level nose-poke response to test the possible reinforcing effects of some components of access to a male. A simple tone stimulus used as a conditioned reinforcer and two odor stimuli, target male bedding and emulsified preputial gland, were tested. None of these contingent events altered responding above or below operant level. Access to the male, which was always accompanied by intromission, immediately increased response rate when it was made contingent upon the nose-poke response. Performance on fixed-ratio schedules was erratic, and response rate was low in comparison to typical food-reinforced responding. An interresponse-time analysis indicated, however, that some effect of the ratio contingency may have been present. In Experiment 2, several modifications of the procedure were tested with the objective of creating a more tractable preparation for behavior analysis. Response type and the hormone delivery method were changed, and 2 target males were used instead of 1. The latter tripled the average number of reinforcers earned in a single session. Differences between sexual and other reinforcers are discussed in terms of procedural, quantitative, and motivational aspects of the sexual reinforcement procedure.

Cardiac function improvement 24 hours after isradipine SRO in patients with chronic stable angina: a double-blind randomized study.

We recently showed that Isradipine, a calcium antagonist from the dihydropyridine group, reduces ischemia and improves ventricular function at rest and during exercise, 2 hours after a single oral dose, in patients with chronic stable angina. In the present study, we evaluated the effects of long acting slow release oral (SRO) Isradipine (5 mg) compared to a placebo in 30 coronary patients with stable chronic angina, randomized in a double blind-fashion. The following parameters were obtained at rest and during submaximal exercise: left and right ventricular (LV, RV) ejection fractions (EF; %) and peak filling rate (PFR; EDV/s), assessed by gated radionuclide angiography, clinical symptoms, electrocardiograms (ECG, ST segment depression; mm), systolic and diastolic blood pressure (SBP and DBP; mm Hg). Patients were then given two oral doses of either Isradipine or placebo (one a day). The same parameters were reassessed, at rest and during n equivalent exercise, 48 hours later (24 hours after the last administration of the drug). The results after Isradipine (n = 14) showed, at rest, a significant increase in LVEF and Pfr (51 +/- 9 to 54 +/- 8 and 1.97 +/- 0.44 to 2.36 +/- 0.71, respectively) and a decrease in DBP (93 +/- 11 to 87 +/- 13); and during exercise, a significant increase in LVEF (51 +/- 11 tot 55 +/- 13) and a decrease in ST segment depression (2.3 +/- 1.9 tot 1.9 +/- 1.6). No significant change was observed after placebo in the other 16 patients. We conclude that even 24 hours after an oral administration, Isradipine SRO maintains its beneficial effects both, at rest on LV systolic and diastolic function and pressure, and during exercise on ECG signs of ischemia with improvement in LV ejection fraction.