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The pharmacodynamic effects of a lower-lipid emulsion of propofol: a comparison with the standard propofol emulsion.

UNLABELLED: Using a randomized, double-blind protocol design, we compared a new lower-lipid emulsion of propofol (Ampofol) containing propofol 1%, soybean oil 5%, and egg lecithin 0.6% with the most commonly used formulation of propofol (Diprivan) with respect to onset of action and recovery profiles, as well as intraoperative efficacy, when administered for induction and maintenance of general anesthesia as part of a "balanced" anesthetic technique in 63 healthy outpatients. Anesthesia was induced with sufentanil 0.1 microg/kg (or fentanyl 1 microg/kg) and propofol 2 mg/kg IV and maintained with a variable-rate propofol infusion, 120-200 microg x kg(-1) x min(-1). Onset times to loss of the eyelash reflex and dropping a syringe were recorded. Severity of pain on injection, speed of induction, intraoperative hemodynamic variables, and electroencephalographic bispectral index values were assessed. Recovery times to opening eyes and orientation were noted. The results demonstrated that there were no significant differences between Ampofol and Diprivan with respect to onset times, speed of induction, anesthetic dose requirements, bispectral index values, hemodynamic variables, recovery variables, or patient satisfaction. However, the incidence of pain on injection was more frequent in the Ampofol group (26% versus 6%, P < 0.05). We conclude that Ampofol is equipotent to Diprivan with respect to its anesthetic properties but was associated with a more frequent incidence of mild pain on injection. IMPLICATIONS: The pharmacodynamic profile of a lower-lipid containing emulsion of propofol (Ampofol) was compared with Diprivan when administered for induction and maintenance of general anesthesia. This preliminary study demonstrated that the two formulations of propofol were equivalent with respect to their induction and maintenance properties. However, Ampofol was associated with a more frequent incidence of pain on injection.

Adult↗

Curvature of the caudal region is responsible for failure of neural tube closure in the curly tail (ct) mouse embryo.

Delayed closure of the posterior neuropore (PNP) occurs to a variable extent in homozygous mutant curly tail (ct) mouse embryos, and results in the development of spinal neural tube defects (NTD) in 60% of embryos. Previous studies have suggested that curvature of the body axis may delay neural tube closure in the cranial region of the mouse embryo. In order to investigate the relationship between curvature and delayed PNP closure, we measured the extent of ventral curvature of the neuropore region in ct/ct embryos with normal or delayed PNP closure. The results show significantly greater curvature in ct/ct embryos with delayed PNP closure in vivo than in their normal littermates. Reopening of the posterior neuropore in non-mutant mouse embryos, to delay neuropore closure experimentally, did not increase ventral curvature, suggesting that increased curvature in ct/ct embryos is not likely to be a secondary effect of delayed PNP closure. Experimental prevention of ventral curvature in ct/ct embryos, brought about by implantation of an eyelash tip longitudinally into the hindgut lumen, ameliorated the delay in PNP closure. We propose, therefore, that increased ventral curvature of the neuropore region of ct/ct embryos imposes a mechanical stress, which opposes neurulation and thus delays closure of the PNP. Increased ventral curvature may arise as a result of a cell proliferation imbalance, which we demonstrated previously in affected ct/ct embryos.

Animals↗

Prostaglandin analog treatment of glaucoma and ocular hypertension.

OBJECTIVE: To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma. DATA SOURCES: Primary and review articles were identified from a MEDLINE search (1966-May 2001) and requested information from product manufacturers. STUDY SELECTION AND DATA EXTRACTION: All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date. DATA SYNTHESIS: The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with beta-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes. CONCLUSIONS: Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.

Amides↗

Travoprost: a potent ocular hypotensive agent.

Travoprost (isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[alpha,alpha,alpha,trifluoro-m-tolyl)oxy]-1butenyl]cyclopentyl]-5-heptenoate) is an isopropyl ester prodrug and a high-affinity, selective FP prostaglandin- receptor full agonist. This prodrug is a synthetic prostaglandin analogue, which in appropriate cases is administered topically for the treatment of glaucoma and ocular hypertension. The isopropyl ester prodrug is rapidly hydrolyzed by esterases in the cornea to the biologically active, free acid. Travoprost has demonstrated preferential affinity and full agonist activity for the FP receptor in the nanomolar range, with no meaningful affinity or activity at other receptors. Like other compounds of this class, the reduction of intraocular pressure by travoprost is due at least in part to increased uveoscleral outflow. Results from phase II and phase III pivotal studies for FDA approval in the United States have demonstrated that travoprost is an effective topical agent for treatment of elevated intraocular pressure in patients with open-angle glaucoma and ocular hypertension. Travoprost is a safe drug, with local side effects including hyperemia, eyelash growth and iris color change. The dosing is once per day in the evening, and storage does not require refrigeration. Travoprost will be a helpful new drug in the medical management of glaucoma.

Animals↗

"Shake hands"; diagnosing a floppy infant--myotonic dystrophy and the congenital subtype: a difficult perinatal diagnosis.

Myotonic dystrophy is a multi-organ disease inherited in a complicated way. Congenital myotonic dystrophy is a distinct entity with severe symptoms leading to a high rate of perinatal morbidity and mortality. The occurrence of congenital myotonic dystrophy often allows a subsequent diagnosis in the mother with important implications for her life, her further pregnancies and offspring. Genetic principles of anticipation and somatic mosaicism are involved and hamper the prenatal diagnostic possibilities. A family is presented in which maternal myotonic dystrophy and congenital myotonic dystrophy were diagnosed after the third pregnancy. The key features leading to the diagnosis were obstetric history, neonatal hypotonia and asphyxia, facial abnormalities in the mother together with the inability to bury eyelashes and delayed release of grip after shaking hands. The disorder is reviewed with respect to clinical symptoms, pathogenesis and genetics.

Adult↗

An update on bimatoprost in glaucoma therapy.

Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the beta-adrenergic antagonist timolol and has consistently provided approximately 1-2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Assessing the cost-effectiveness of switching from a beta-blocker to latanoprost in the treatment of ocular hypertension.

Glaucoma is a pathological condition whose most important risk factor is increased intraocular pressure (IOP). The medical treatment of glaucoma essentially consists of compounds that are able to decrease the IOP. The compounds discussed in this review act in a different way, beta-blockers mainly inhibit the production of aqueous humor, whereas latanoprost decreases the resistance in the outflow channels. beta-Blockers are compounds with a well-known efficacy and safety profile and they are fairly inexpensive. Their systemic and local side effects are mainly cardiovascular and pulmonary adverse events, dry eye and keratopathy. Latanoprost, which has recently been introduced into the market, has been shown to be equally as effective, or better in lowering IOP in patients than timolol, although it is more expensive. Systemic reported side effects are anecdotal; local hyperaemia, keratopathy, hypertrichosis, increased pigmentation of eyelashes and iris, uveitis and cystoid macular oedema have been reported. A comparison of costs reveals that a 1-year therapy with timolol ophthalmic solution starts from 11.00 Euros and can reach 146.00 Euros for the most expensive preservative-free 1-day dispenser packages (approximately 13.5 times higher). For latanoprost once-daily administration, the cost for 1 years therapy is 98.55 Euros, approximately six times higher than generic or brand 0.5% timolol applied twice-daily. What are the factors influencing a change in therapy from beta-blockers to latanoprost? The only good reason is represented by a further deterioration in the visual field. This may occur, despite a significant reduction in IOP, because the reached IOP is not sufficient enough to avoid further deterioration because the patient's work or social activities do not allow a correct daily dosage of the compound (bad compliance); or as a result of treatment suspension, because of the development of systemic and/or local side effects. Changes in therapy must always be related to a failing control of the disease, as any therapeutic modification leading to an increase in the number of visits and additional examinations, consequently enhances the costs.

Adrenergic beta-Antagonists↗

[Uveomeningoencephalitis: report of 2 cases].

The uveomeningoencephalitic syndromes are inflammatory diseases, more prevalent in oriental patients, without sexual predilection and with mean age of 30 years. From the clinical point of view they affect the uvea, retina, meninges, the central nervous system and skin and in most cases the onset is followed by three phases: the meningoencephalitic phase, the acute ophthalmic phase and the dermatologic phase. These includes the Harada disease, the Vogt-Koyanagi disease, the Behçet disease and the idiopathic forms. The Vogt-Koyanagi syndrome is a chronic and severa bilateral exudative uveitis associated with whitening of the hair and eyelashes and varying signs of meningeal irritation, less frequent than in Harada's disease. The Harada syndrome is a posterior uveitis accompanied by signs of meningeal irritation, increased protein levels and pleocytosis of the cerebrospinal fluid. The Behçet's disease is a relapsing illness, characterized by oral and genital aphtous ulcers and ocular inflammation. In many cases there are additional features; in 10 to 25 percent of the cases there are neurologic involvement, and any portion of the nervous system may be affected. The authors studied two cases of uveomeningoencephalic syndrome, one case of Vogt-Koyanagi-Harada disease (case 1) and another of Behçet disease (case 2). The case 1 was a white Brazilian forty-five year-old man, with a acute headache, mental confusion and signs of meningeal irritation. The cerebrospinal fluid was a inflammatory one, with increased lymphocytes and monocytes, the one month after the patient developed bilateral uveit. The patient complicated with amblyopia of the left eye and a Korsakoff syndrome. There was no correlation in the literature of the Korsakoff syndrome and the uveomeningoencephalitic syndrome. The case 2 was a white Brazilian, twenty-four year-old man, with two episodes of meningitis, genital recurrent aphtous ulcers and uveitis in the right eye, with latter blindness of this eye. Some considerations about the etiopathogenic aspects are done and about the controversial use of corticoids in the treatment of these syndromes.

Adrenal Cortex Hormones↗

Recurring chemotherapy-associated alopecia areata: case report and literature review.

A 52-year-old woman with stage IIIC ovarian cancer and stage IA uterine cancer experienced recurring alopecia areata of her eyebrows, eyelashes, arms, legs, and pubic area beginning 5 months after completing chemotherapy with paclitaxel and carboplatin. The condition recurred in a cyclic fashion over the ensuing months. Alopecia is a well-recognized adverse event associated with chemotherapy; however, to our knowledge, this cyclic pattern of alopecia has not been reported in a patient with cancer. Our report of a cancer survivor who experienced cyclic alopecia areata indicates that this condition may be related to autoimmune changes instigated by chemotherapy. Oncology health care practitioners should evaluate unusual clinical cases of alopecia for underlying pathology.

Alopecia Areata↗

Tetraploid/diploid mosaicism with generalized aggressive periodontitis.

BACKGROUND: Changes of chromosome number diploid to triploid or tetraploid states are rare in human pregnancies, where the main clinical features of tetraploidy are delayed growth and/or craniofacial abnormalities. The present report describes the oral features of tetraploid/diploid mosaicism. Although the medical literature described the physical manifestations of this genetic abnormality, the oral features of this disorder were not previously described. METHODS: A 13-year-old patient presented because of his severe periodontal conditions. Clinical, radiological, microbiologic, immunologic, and genetic examinations were conducted. RESULTS: Long eyelashes and mandibular micrognathia were noticeable in his extraoral examination. Intraoral examination revealed significant generalized edema of the gingiva and severe sulcular bleeding on probing. Generalized maxillary and mandibular alveolar destruction was determined with radiographic examination. Actinobacillus actinomycetemcomitans was also detected in his subgingival samples. He was diagnosed as generalized aggressive periodontitis. His medical cytogenetic examination revealed 92,XXYY (25%)/46,XY (75%) karyotype indicating tetraploid/diploid mosaicism. He was given initial and advanced periodontal therapy and he is currently under a routine follow-up period. CONCLUSIONS: This report provides information on the oral characteristics of tetraploid/diploid mosaicism and describes periodontal treatment. Severe periodontal conditions such as aggressive periodontitis may accompany tetraploid/diploid mosaicism subjects and these patients should be frequently seen by their dental practitioners. It is suggested that initial and/or advanced periodontal procedures may be a way of treating tetraploid/diploid mosaicism subjects with aggressive periodontitis. The importance of physical examination and medical consultation is also discussed.

Adolescent↗

A preliminary risk-benefit assessment of latanoprost and unoprostone in open-angle glaucoma and ocular hypertension.

Latanoprost and unoprostone (isopropyl unoprostone) represent the first commercially available prostaglandin analogues to be used for the treatment of glaucoma. Both compounds reduce intraocular pressure by enhancing uveoscleral outflow. Latanoprost, when used once daily in the evening, produces a greater reduction in pressure than timolol. Latanoprost produces mild conjunctival hyperaemia compared with timolol in some patients. Darkening of the irides has been reported, especially in green-brown, yellow-brown and blue/grey-brown irides. Hypertrichosis and hyperpigmentation of the eyelashes have also been demonstrated. Although latanoprost has not been proven to cause uveitis or cystoid macular oedema, case reports of an association exist. Latanoprost does not produce systemic adverse effects nor does it alter routine blood analyses. Unoprostone, when given twice daily, produces less of a reduction in intraocular pressure than timolol or latanoprost. Three times daily use may be required to approach the effectiveness of timolol. Unoprostone may have a similar adverse effect profile to latanoprost, but may to cause more corneal epithelial problems. Unoprostone is also not known to cause systemic adverse effects. Both agents are welcome additions to the treatment of glaucoma. However, additional studies and more experience are needed with each agents.

Dinoprost↗

Travoprost.

Travoprost is a synthetic ester prodrug of a prostaglandin F(2alpha) analogue used in the treatment of open-angle glaucoma and ocular hypertension. Intraocular travoprost 0.004% once daily was significantly more effective at reducing intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension than placebo or timolol 0.5% twice daily and was at least as effective as latanoprost 0.005% once daily in randomised, double-blind studies. When used as adjunctive therapy with timolol 0.5% twice daily in patients with elevated IOP not adequately controlled by timolol alone, travoprost 0.004% showed significant additional IOP reduction in a randomised double-blind trial. Travoprost 0.004% was well tolerated in clinical trials. The majority of adverse events such as ocular hyperaemia and eyelash changes were mild and resolved without treatment.

Adult↗

[Down syndrome associated with clinical manifestations of Kabuki syndrome: report of a case]

OBJECTIVE: To describe an atypical case of Down syndrome presenting with additional clinical manifestations that might be components of Kabuki (Niikawa-Kuroki) syndrome.CLINICAL REPORT: We report the clinical history of a 19-month-old girl with a 47,XX, +21 karyotype, who presented brachycephaly, flat face, long palpebral fissures, eversion of the lateral portion of the lower eyelids, arched eyebrows with sparse lateral regions, long eyelashes, epicanthus, cortical cataract, small ears, protruding tongue, muscular hypotonia, developmental delay, hyperflexibility of joints, brachydactyly, and dermatoglyphic abnormalities.CONCLUSION: The diagnosis of Down syndrome was confirmed cytogenetically. However, the presence of additional anomalies - mainly in the ocular region - suggested that the child might also have the Kabuki syndrome.

Journal Article↗

[Co-induction in ambulatory anesthesia].

BACKGROUND: Co-induction in anesthesia is very useful: synergistic effects of two inductional drugs may lower the dose regimen and the incidence of adverse effects. The aim of this study was to investigate and compare two anesthesiological techniques for short-lasting gynecological procedures in outpatient anesthesia. A total of 80 patients scheduled for surgical termination of pregnancy were randomly assigned into two equal groups--control and co-induction group. METOHDS: The first group of patients received atropine 0.5 mg i.v., alfentanil 0.5 mg i.v. and propofol as a fractionated i.v. bolus until the loss of eyelash reflex. The second group received atropin 0.5 mg, alfentanil 0.5 mg, midazolam 3 mg and propofol in the same manner as the first group. Anesthesia was maintained with propofol increments. Cardiovascular parameters, parameters of post anesthesia recovery and the adverse effects were registered. RESULTS: In patients receiving midazolam inductional dose of propofol was significantly lower, whereas cardiovascular parameters were not significantly different. The recovery after anesthesia was slightly longer after co-induction, but it was not of great clinical significance. The reduction of the adverse effects was found in the co-induction group. CONCLUSION: The results of the study showed that co-induction of midazolam-propofol in comparison with propofol alone for outpatient anesthesia had the following advantages: the reduction of propofol dose, better quality of anesthesia and the reduction of the adverse effects. Recovery was faster in the group that didn't receive midazolam, but it was not of great clinical significance. The conclusion is that co-induction with the combination midazolam-propofol has the advantage in outpatient procedures.

Abortion, Induced↗

Bipedicled tarsoconjunctival flap in advanced cicatricial entropion. Case report.

In the treatment of cicatricial entropion it may be necessary to bring new tissue to the lid margin after this has been split and the eyelashes have been everted. A bipedicled tarsoconjunctival flap from the proximal part of the tarsus forms a stable and non-irritant new lid rim for both the upper and the lower eyelid. The donor site is closed by advancement of the conjunctiva of the fornix. Three case histories are presented.

Adult↗

Proton irradiation of malignant uveal melanoma. A five year follow-up of patients treated in Uppsala, Sweden.

Twenty patients with malignant uveal melanoma were treated at the The Svedbergh cyclotron in Uppsala from 1989 to 1991. Each tumour received a total dose of 54.6 Gy in four equal fractions on four following days. After treatment the melanoma in all eyes showed decrease in size combined with irradiation retinopathy. In eight patients the treatment was successful after five years. Nine eyes had to be enucleated, two due to recurrence and seven due to neovascular glaucoma. Three patients died, two from metastases and one from heart disease. In all patients the visual acuity was dependent on the distance between the irradiation field and the macula or optic nerve. Each patient suffered from transient post irradiation skin erythema and permanent loss of eyelashes and eyebrows when these were included in the irradiation field. The development of secondary glaucoma was positively correlated with tumour volume, but not to the age or sex of the patients. Histological examination of all the enucleated eyes revealed residual viable tumour without obvious radiation damage: mitotic figures were not identified. MRI examination, performed before and after treatment, demonstrated a marked shift in water binding properties after irradiation. The final visual acuity was dependent on the location of the tumour.

Adult↗

Prostaglandin analogs in the treatment of glaucoma.

Prostaglandin (PG) analogs are some of the most recent additions to the list of ocular hypotensive medications. Two analogs of naturally occurring PGs are available commercially, isopropyl unoprostone (Rescula [Ciba Vision, Atlanta, GA]) and latanoprost (Xalatan [Pharmacia & Upjohn, Bridgewater, NJ]). Presently, latanoprost 0. 005% is the only PG analog commercially available in the United States. These agents have been shown to be the most effective topical medications for reducing intraocular pressure. They have a different mechanism of action than other ocular hypotensives, and act primarily by increasing uveoscleral outflow. Because of this, PGs have a substantial additive effect when used with agents that reduce aqueous production (eg, beta blockers or carbonic anhydrase inhibitors) or that increase trabecular outflow facility (eg, pilocarpine). Local side effects include mild conjunctival hyperemia and local irritation, darkening of iris color, increased growth of eyelashes, and a possible association with cystoid macular edema or iritis in some patients with other risk factors. No systemic side effects have been proven to be caused by latanoprost. Recommended dosing is once daily at bedtime.

Animals↗

Trichotillomania: clinical aspects and treatment strategies.

Trichotillomania is a disorder of compulsive hair pulling that often results in alopecia. The clinical features include the pulling of hair from the scalp, eyebrows, and eyelashes, sometimes symmetrically; pubic and other bodily hair may also be plucked. The disorder is present in 0.6% of college students. The majority of sufferers who seek treatment are female, with usual age of onset between 11 and 16 years. Trichotillomania can occur in a wide variety of psychiatric disorders, and patients with the condition may be more likely to have a lifetime diagnosis of depression or an anxiety, eating, or substance abuse disorder. Although empirically derived treatment guidelines are still lacking, the current literature suggests that behavior therapy and pharmacotherapy are the most efficacious treatments for adult trichotillomania. Controlled trials with pharmacotherapy (clomipramine) have shown significant reductions in hair pulling over the short term. Controlled investigations of behavior therapy have not been conducted, but several treatment series suggest efficacy. At least three reports also suggest that behavior therapy and pharmacotherapy bring some improvement in childhood trichotillomania, although this has not been empirically studied. A case illustrating the combination of behavior therapy techniques and pharmacotherapy in the treatment of trichotillomania is presented.

Adolescent↗