Is halofantrine ototoxic? Experimental study on guinea pig cochlea model.

INTRODUCTION: Halofantrine is a newly developed antimalarial drug used for the treatment of Plasmodium falciparum malaria. The introduction of this drug has been delayed because of its possible side effects, and due to insufficient studies on adverse reactions in humans. There have been no studies investigating its effect on hearing. METHODS: Thirty guinea pigs were divided into three groups: a control group, a halofantrine therapeutic dose group and a halofantrine double therapeutic dose group. One cochlea specimen from each animal was stained with haematoxylin and eosin and the other with toluidine blue. RESULTS: No changes were detected in the control group. The halofantrine therapeutic dose group showed loss and distortion of inner hair cells and inner phalangeal cells, and loss of spiral ganglia cells. In the halofantrine double therapeutic dose group, the inner and outer hair cells were distorted and there was loss of spiral ganglia cells. CONCLUSION: Halofantrine has mild to moderate pathological effects on cochlea histology, and can be considered an ototoxic drug.

The risk of recurrent stroke after intracerebral haemorrhage.

BACKGROUND AND AIM: The risks of recurrent intracerebral haemorrhage (ICH) vary widely (0-24%). Patients with ICH also have risk factors for ischaemic stroke (IS) and a proportion of ICH survivors re-present with an IS. This dilemma has implications for prophylactic treatment. This study aims to determine the risk of recurrent stroke events (both ICH and IS) following an index bleed and whether ICH recurrence risk varies according to location of index bleed. PATIENTS AND METHODS: All patients diagnosed with an acute ICH presenting over an 8.5 year period were identified. Each ICH was confirmed by reviewing all of the radiology results and, where necessary, the clinical case notes or post-mortem data. Recurrent stroke events (ICH and IS) were identified by reappearance of these patients in our stroke database. Coronal post-mortem results for the same period were also reviewed. Each recurrent event was reviewed to confirm the diagnosis and location of the stroke. RESULTS: Of the 7686 stroke events recorded, 768 (10%) were ICH. In the follow-up period, there were 19 recurrent ICH and 17 new IS in the 464 patients who survived beyond the index hospital stay. Recurrence rate for ICH was 2.1/100 in the first year but 1.2/100/year overall. This compares with 1.3/100/year overall for IS. Most recurrences were "lobar-lobar" type. CONCLUSION: The cumulative risk of recurrent ICH in this population is similar to that of IS after the first year.

Colonic resection for colovesical fistula: 5-year follow-up.

OBJECTIVES: The outcome of colovesical fistula management may be unsatisfactory; complications are reported in up to 45% of patients. Published studies are retrospective and tend to lack standardized management strategies and long-term follow-up. This cohort study assesses a policy of resection of colovesical fistulae in continuity with any distal colorectal stricture, and includes 5-year follow-up. METHOD: All patients undergoing surgery in our institution for colovesical fistula between February 1991 and April 1995 were entered into the study. The fistulae were resected in continuity with any distal bowel stricture, according to a standard single-stage operative protocol. Postoperative mortality and morbidity were recorded, and prospective review was undertaken at April 2000. RESULTS: Nineteen consecutive patients entered the study. The source of the fistula was diverticular disease (n = 14), colorectal cancer (n = 3), trauma (n = 1) or Crohn's (n = 1) disease. Thirteen patients had a colorectal stricture. One patient died due to ischaemic colitis within 30 days of surgery. Eleven other patients died of unrelated causes before April 2000, in whom there was no evidence of fistula recurrence before death at a median of 37 months after operation (range 2-95 months). At 5-year follow-up there was no evidence of fistula recurrence in the seven remaining patients. CONCLUSIONS: A policy of resection of the fistula and associated colorectal stricture with primary bowel anastomosis and bladder drainage, resulted in no recurrences and low morbidity. However comorbidity is important in this patient population, most of whom will die from unrelated causes within a few years.

Late traumatic flap dislocation after laser in situ keratomileusis.

Three patients who had laser in situ keratomileusis (LASIK) experienced severe direct corneal trauma 3 to 38 months postoperatively. Flap dislocation resulted in all 3 patients. Presentation following trauma ranged from a few hours to 9 days. All patients were successfully managed by surgical flap repositioning, and all maintained a best corrected visual acuity of 20/20. A literature review of traumatic flap dislocation cases and the most recent methods of diagnosis and management are included.

Minimizing the risk of recutting with a Hansatome over an existing Automated Corneal Shaper flap for hyperopic laser in situ keratomileusis enhancement.

We report a case series of 4 eyes to discuss the intraoperative complications of recutting a laser in situ keratomileusis (LASIK) flap with a Hansatome microkeratome over an existing 160 microm Automated Corneal Shaper flap for the retreatment of hyperopia. In the eyes that were recut, slivers of stroma were apparent on reflection of the flap; the slivers were located centrally in the 180 microm eye and peripherally in the 160 microm eyes. Recutting a flap for LASIK retreatment runs the risk of visually significant stromal irregularities.

Diffuse lamellar keratitis: isolation of endotoxin and demonstration of the inflammatory potential in a rabbit laser in situ keratomileusis model.

PURPOSE: To systematically examine sources of endotoxin contamination in eye centers as a potential cause of diffuse lamellar keratitis (DLK) and to demonstrate the inflammatory potential of endotoxin in a rabbit model of laser in situ keratomileusis (LASIK) surgery. SETTING: University of Calgary, Calgary, Alberta, Canada. METHODS: In this prospective study, all water sources that routinely come in contact with LASIK instruments, including sterilizer reservoirs, eyedrops, microkeratome blades, and cleaning solutions, were examined for endotoxins at 5 eye centers. Bacterial cultures were performed on water samples from 5 sterilizer reservoirs. A LASIK flap was created in 8 rabbit eyes using an Automated Corneal Shaper microkeratome (Bausch & Lomb). The flaps were reflected, and a dose of endotoxin at various concentrations was placed on the interface. After 1 minute, the flap was irrigated and repositioned. The rabbit eyes were examined daily with a slitlamp biomicroscope for 3 days for the development of DLK, which was classified on a scale from grade 1 to 4 (mild to severe). The rabbits were killed at the conclusion of the study, and the interfaces were stained to rule out infectious etiologies. RESULTS: Endotoxin was detected in significant concentrations in tap water, filtered and distilled water, instrument washbasins, and sterilizer reservoirs at all 5 centers. The cultures of the water samples taken from the sterilizer reservoirs ranged from no growth to the presence of >100 colony-forming units of Flavobacterium and Pseudomonas aeruginosa. Endotoxins caused DLK-like interface inflammation in all eyes tested. Examination of stained scrapings showed no microorganisms in the interface of the rabbit eyes. CONCLUSION: Endotoxin contamination was detected in water sources that routinely come in contact with LASIK instruments. Endotoxins were capable of inducing interface inflammation in a rabbit model and may therefore be a significant factor in epidemic DLK.

Accuracy of Orbscan pachymetry measurements and DHG ultrasound pachymetry in primary laser in situ keratomileusis and LASIK enhancement procedures.

PURPOSE: To assess the accuracy and variability in pachymetry measurements obtained by Orbscan and by DGH ultrasound in primary laser in situ keratomileusis (LASIK) and LASIK enhancement procedures. SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS: A retrospective analysis of 906 consecutive primary LASIK and 183 consecutive LASIK enhancement procedures for which preoperative DGH ultrasound and Orbscan pachymetry measurements were obtained. The theoretical residual corneal thickness was compared to measurements by both instruments in 60 eyes that had primary procedures and enhancements. RESULTS: In primary LASIK eyes, the DGH ultrasound measurements were thicker than the Orbscan measurements by a mean of 18.4 microm +/- 17.4 (SD). The DGH ultrasound measurements were thicker than the Orbscan measurements by a mean of 50.1 +/- 40.7 microm in preenhancement pachymetry measurements. The DGH ultrasound measurements were consistent with theoretical residual corneal thickness, 493.0 +/- 42.0 microm versus 487.0 +/- 31.0 microm (P =.65), while Orbscan measurements were statistically less than the theoretical residual corneal thickness, 431.0 +/- 42.0 microm versus 468.0 +/- 39.0 microm (P =.0001). CONCLUSION: DGH ultrasound was a more accurate measurement of corneal pachymetry than Orbscan. The discrepancies between DGH ultrasound and Orbscan pachymetry measurements were more prominent in eyes that had had LASIK.

Postoperative complications in laser in situ keratomileusis.

Laser in situ keratomileusis (LASIK) has become the most common procedure to correct refractive errors in North America. Increasing numbers of patients and surgeons are choosing LASIK in the management of low and moderate myopia, astigmatism, and hyperopia. LASIK presents a unique group of postoperative challenges and complications. It is important to be able to identify these complications in the early and late postoperative periods and to provide effective management. In this article, we review the most commonly encountered early and late postoperative complications after LASIK and the most current methods in prevention and treatment.

Touch-free in situ investigation of ancient Egyptian pigments.

Some of the pigments painted on the Funerary Stele of Amenemhat (ca. 2000 B.C.) exhibited at the Egyptian Museum, Cairo and on the walls of the Tomb of Userhat (ca. 1420 B.C.), a rock-cut tomb in Thebes, Egypt, were investigated in situ using both a convenient home-made hand-held type of X-ray diffractometer and a commercial X-ray fluorescence spectrometer in a complementary way under touch-free conditions. CaCO3.3MgCO3 (huntite) was found in the white-painted parts of these two ancient monuments. An arsenic (As)-bearing phase was detected in the yellow-painted parts of the latter monument. The occurrence of huntite in Egypt has not been reported previously.

Laser in situ Keratomileusis Flap Complications and Management.

PURPOSE: To provide detailed descriptions of intraoperative and postoperative flap complications independent of the microkeratome. Management of these complications is discussed. METHODS: Complications have been assimilated and categorized based on our past experiences and those of others. Methods for managing these complications are discussed. RESULTS: Positive results were considered to be successful resolution of the flap complication, which typically occurs in the majority of cases. CONCLUSION: LASDX is a technically difficult surgical procedure with unique complications. Excellent flap management both intraoperatively and postoperatively is essential to maximize visual outcome. Some flap complications are easily managed and others require immediate expert surgical intervention to preserve good visual outcomes. [J Refract Surg 2000;16(suppl):S223-S225].

Prevention and Management of Microkeratome-related Laser in situ Keratomileusis Complications.

PURPOSE: To review the most commonly encountered laser in situ keratomileusis (LASIK) microkeratome-related complications, and the most up-to-date methods in their prevention and treatment. METHODS: A review of microkeratome-related complications including epithelial complications, bleeding, thin flap, button hole, free cap, incomplete pass, and corneal perforation was conducted. The most recent techniques for prevention and treatment of each complication were included. RESULTS AND CONCLUSION: Microkeratome complications are difficult to predict. With proper attention to anatomical and mechanical considerations, many can be reduced or prevented. [J Refract Surg 2000;16(suppl):S226-S229].

Synthesis of positively charged phthalocyanines and their activity in the photodynamic therapy of cancer cells.

Positively charged zinc containing or metal free phthalocyanines 6a-c and 7a-c were prepared via a three step procedure starting from 4-nitrophthalonitrile. The phthalocyanines contain alkyl chains of different length in order to influence the hydrophilic vs lipophilic character of the compounds. The partition between a hydrophilic (water) and lipophilic (octanol-1) phase was determined, and the photoredox activities were investigated. Initial results on the photodynamic activity of these compounds were compared with those of Dougherty's Photofrin II on different malignant and non-malignant cell lines (XP 29MAmal, CX1, HeLa, S180 and NO17). Positively charged phthalocyanines in vitro showed a higher photodynamic activity than Photofrin II.

Coherent Radiation for X-Ray Imaging-The Soft X-Ray Undulator and the X1A Beamline at the NSLS.

An undulator-based beamline was built and commissioned at the National Synchrotron Light Source to provide tunable coherent radiation in the 200-800 eV range. The low emittance of the storage ring means that the undulator source has high brightness so that a large flux of coherent x rays is delivered to experimental stations. The beamline uses a horizontally dispersing bichromator that allows two experiments to run simultaneously, making use of the first and second harmonics of the undulator output. In addition, the use of horizontally deflecting optics enables the beamline alignment to be insensitive to electron beam motion since the horizontal electron beam size is quite large. The beamline and its performance are discussed with emphasis on the optics and on stability, radiation, and vacuum considerations.

The interior of a whole and unmodified biological object--the zymogen granule--viewed with a high-resolution X-ray microscope.

We report the ability of focused soft X-rays to visualize at spatial resolution well beyond that of the optical microscope (less than 100 nm) the interior of a small, whole biological object without fixation, staining, dehydration or sectioning. Quantitative estimation of its protein content with unique femtogram sensitivity is also reported. The present results represent a significant step towards the goals of natural imaging and chemical mapping of biological structures with soft X-rays.