Acetazolamide in hemodialysis patients: a rational use after ocular surgery.

Acetazolamide is a weak diuretic used to decrease production of aqueous humor in the eye. Hemodialysis patients undergoing ocular surgery may benefit from acetazolamide; however, no pharmacokinetic data are available for this group of patients. We report a patient who received acetazolamide 250 mg every 6 hours after ophthalmic surgery and developed reversible neurological side effects associated with very high plasma concentrations. Using pharmacokinetic analysis, we suggest an alternate administration of acetazolamide for end-stage renal patients.     

Radiographical documentation of direct injury of the intracanalicular segment of the optic nerve in the orbital apex syndrome

In the radiographical evaluation of the orbital apex syndrome, standard radiographs, tomograms, and computed tomographic scans have proved useful in the demonstration of the bony pathology, especially for optic canal fractures. The limitation of these methods, however, remains in their inability to provide accurate delineation of the associated soft tissue pathology, including the presence of optic nerve sheath hematoma. Recent developments in computer technology and graphic imaging are now available to provide an accurate three-dimensional radiographical analysis of the extent of skeletal and soft tissue injury in the orbital apex syndrome. The physician, in essence, can perform a radiographical "living autopsy". The technique was used to evaluate a patient with bilateral apex syndrome. It clearly showed that a severe direct injury to the intracanalicular portion of the optic nerve was responsible for the development of blindness in this patient. The progression of optic nerve injury, from perineural sheath hematoma to the ultimate development of optic nerve atrophy and fibrosis, was radiographically documented.     

Rigid fixation: variations in osteotomy design and technique

The application of rigid fixation devices has expanded the craniomaxillofacial surgeon's armamentarium and allows greater versatility of osteotomy design and fixation. Further studies are under investigation to determine the degree of "interference" with growth as a result of application of rigid fixation devices. Our preliminary thought is that bone is dynamic and "liquid" enough to allow the driving forces of the developing cerebral tissue to remodel and recontour the bone tissue into a normal configuration and contour. Problems with relapse and resorption appear greatly reduced for both bone grafts and bone flaps. As the biomaterials industry continues to perfect rigid fixation devices, further advances will be forthcoming.     

Organization of cyclic AMP-dependent connexin 43 in Swiss 3T3 cells attached to a cellulose substratum.

We have previously shown that the adenylyl cyclase, which produces cyclic AMP (cAMP) in Swiss 3T3 cells, is activated by their attachment to a cellulose substratum (Cuprophan, CU). This substratum adsorbs vitronectin poorly, prevents cell spreading and causes them to aggregate. By contrast, cells spread out on polystyrene and contain low concentrations of cAMP. We have found that Connexin 43 (Cx 43) gap junction plaques are involved in this cell aggregation. MDL 12330 A, a specific inhibitor of adenylyl cyclase, prevented cell aggregation on CU and abolished Cx 43 channel clustering. But forskolin, a direct activator of adenylyl cyclase, and SBr cAMP, a cell-permeable analogue of cAMP, caused Cx 43 channel clustering in cells attached to polystyrene. Hence, Cx 43 channel clustering is regulated by cAMP in Swiss 3T3 cells. In addition, neither brefeldin A nor monensin (inhibitors of transit through the endoplasmic reticulum and Golgi apparatus), abolished Cx 43 channel clustering in cells aggregated on CU. Thus, the Cx 43 that form clusters in cells attached to CU are not dependent upon the trafficking of Cx 43 from intracellular storage sites, but are probably reorganised from the plasma membrane.     

POL32, a subunit of the Saccharomyces cerevisiae DNA polymerase δ, defines a link between DNA replication and the mutagenic bypass repair pathway

Pol32 is a subunit of Saccharomyces cerevisiae DNA polymerase δ required in DNA replication and repair. To gain insight into the function of Pol32 and to determine in which repair pathway POL32 may be involved, we extended the analysis of the pol32Δ mutant with respect to UV and methylation sensitivity, UV-induced mutagenesis; and we performed an epistasis analysis of UV sensitivity by combining the pol32Δ with mutations in several genes for postreplication repair (RAD6 group), nucleotide excision repair (RAD3 group) and recombinational repair (RAD52 group). These studies showed that pol32Δ is deficient in UV-induced mutagenesis and place POL32 in the error-prone RAD6/REV3 pathway. We also found that the increase in the CAN1 spontaneous forward mutation of different rad mutators relies entirely or partially on a functional POL32 gene. Moreover, in a two-hybrid screen, we observed that Pol32 interacts with Srs2, a DNA helicase required for DNA replication and mutagenesis. Simultaneous deletion of POL32 and SRS2 dramatically decreases cellular viability at 15 °C and greatly increases cellular sensitivity to hydroxyurea at the permissive temperature. Based on these findings, we propose that POL32 defines a link between the DNA polymerase and helicase activities, and plays a role in the mutagenic bypass repair pathway. Received: 25 May 2000 / Accepted: 3 July 2000     

A double-blind, placebo-controlled study of the effects of lithium on cognition in healthy subjects: mild and selective effects on learning

Background: Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium. The aim of the study was to look at the effect of lithium in normal subjects (N=30) taking lithium for 3 weeks. A comprehensive battery was used to assess attention and memory. Methods: Subjects were randomized to double-blind treatment with either lithium (N=15) or placebo (N=15) for a 3-week period. Thirteen participants in the lithium group and 15 in the placebo group completed the study. The lithium and placebo were administered twice daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The initial daily dose was calculated according to the Pepin formula to achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive performance (attention, memory) was assessed in each subjects during three periods, i.e. at baseline, after 3 weeks of lithium or placebo, and 2 weeks after discontinuation of study medication. Results: In short-term memory tasks, the performance of subjects in the lithium group was worst 3 weeks after lithium treatment compared to 2 weeks after discontinuation. In long-term memory, a significantly higher number of words was recalled by the placebo group but not the lithium group. Conclusions. Lithium may have an effect on learning when long-term explicit memory test are administered repeatedly. It means that the practice effect when a subject performs the same task several times is less in the lithium-treated group than in the placebo group. This practice effect is related to the learning of a task.     

Some technical improvements for the voltage clamp with the double sucrose gap

Summary A new double sucrose gap chamber using electrodes of high stability and low resistance is described. The size of each sucrose gap and the central node can be modified independently so that this chamber is suitable for research on multicellular or unicellular excitable preparation under voltage clamp conditions. The shape of the central channel is made so as to reduce the series resistance between the preparation and the recording electrode to a minimum. A window made in the floor of the chamber allows to observe the preparation under a microscope.This work was performed under the I.N.S.E.R.M. grant no. 17.75.40.     

Patient compliance and blood pressure control on a nuclear-powered aircraft carrier: impact of a pharmacy officer

The impact of a pharmacy officer on patient compliance and blood pressure control on a deployed nuclear-powered aircraft carrier for a 2-week at-sea period was evaluated. Before any counseling by a pharmacy officer, 43 crewmembers on chronic medications anonymously completed a compliance questionnaire. The pharmacy officer then counseled these crewmembers. A follow-up compliance questionnaire was completed 2 weeks later. After counseling, compliance had increased 58% (p < 0.0001) from compliance measured before counseling. The pharmacy officer also initiated therapeutic interventions. Among 26 crewmembers diagnosed as hypertensive, preintervention blood pressure (BP) measurements were obtained. Ten to 14 days after the initial BP measurement, BP was remeasured. After intervention, 31% (p < 0.02) more crewmembers were at BP goal compared with before intervention. A pharmacy officer, working closely with a medical officer, improved patient compliance and blood pressure control. One problem identified was that these warships require computer software that can prospectively identify drug-drug interactions.