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.     

Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine.

Bacterial glutamine synthetase (GS; EC 6.3.1.2) was previously shown to be inhibited by nine end products of glutamine metabolism. Here we present four crystal structures of GS, complexed with the substrate Glu and with each of three feedback inhibitors. The GS of the present study is from Salmonella typhimurium, with Mn2+ ions bound, and is fully unadenylylated. From Fourier difference maps, we find that L-serine, L-alanine, and glycine bind at the site of the substrate L-glutamate. In our model, these four amino acids bind with the atoms they share in common (the "main chain" +NH3-CH-COO-) in the same positions. Thus on the basis of our x-ray work, glycine, alanine, and serine appear to inhibit GS-Mn by competing with the substrate glutamate for the active site.     

Infantile right hemisphere injury: a case report with MRI and 13 year follow-up

Serial neuropsychological findings were obtained in a case of infantile right parietal injury who was studied over a 13 year follow-up period. Magnetic resonance imaging at age 13 years documented extensive injury to the right hemisphere, particularly the parietal region. Serial examinations at age 7 and 13 years showed intact visual attention, normal expression and processing of affect and variable visuospatial abilities. However, intellectual development was generally depressed. Implications of these findings for recovery from early brain injury are discussed.     

Cerebral metabolic and vasopressin and oxytocin responses during osmotic stimulation in conscious rats

Intravenous infusion of hypertonic saline increased plasma [Na (+) ] and osmolality and induced a short-latency drinking response. These changes were associated with increased glucose utilization in the supraoptic and paraventricular nuclei and neural lobe, and decreases in the medial septum and nucleus ambiguus. The increases in glucose utilization were more accentuated in the supraoptic nuclei than in paraventricular nuclei, indicating that they are more sensitive to osmotic stimulation than the paraventricular nuclei. In association with enhanced activity in the hypothalamo-neurohypophysial system, plasma vasopressin and oxytocin concentrations increased, with a preferential increase of oxytocin over vasopressin. The hormonal contents in the neural lobe were not depleted by the osmotic stimulus despite the large increases of their concentrations in the plasma.     

Evaluating emergency medical services: Quasi-experimental outcome studies

The need to evaluate expensive, dramatic, and politically sensitive emergency medical services programs when classical controlled trials are neither ethically nor practically possible can be satisfied by quasi-experimental designs. The sequential implementation of paramedic services in several suburban areas provided a natural experimental situation in which to evaluate whether addition of the service could significantly alter the outcome of cardiac emergencies compared to the basic emergency medical technician program previously available. Before measurements and after measurements were made in a study area plus two control areas: one with paramedic services in both time periods and the other with emergency medical technician service throughout. Preliminary results indicate successful resuscitation increased from 20% to 32% (p less than .05) and discharge from the hospital went from 8% to 18% (p less than .01). The implications for program and policy decisions are noted. Development of studies that evolved from this work are outlined.     

Soft tissue sarcomas of adults: state of the translational science.

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.