Topiramate in migraine prevention: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase. RESULTS: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Defining the physiologically normal coating and pathological deposit: an analysis of sulfur-containing moieties and pellicle thickness on hydrogel contact lenses.

PURPOSE: Historically, biochemical studies of the interaction between tears and hydrogel contact lenses have not been coordinated with the study of the morphological ultrastructure of the phenomena. Moreover, terms that have distinct and different meanings--pellicle, coating, deposit, and biofilm--have been used interchangeably and often incorrectly when applied within the context of the general field of contact lens biotechnology to describe the tear-polymer interaction. We describe our elucidation of morphological and elemental characteristics of the normal pellicle that forms on the lens surface and urge standard use of the word "pellicle" to specify this entity. METHODS: Fourteen worn hydrogel lenses (8 Group 1 and 6 Group 4 lenses according to the FDA classification) were rinsed, quartered, and fixed or dried, depending on the analysis to be performed. Scanning electron microscopy (SEM) was used to examine the morphology of the pellicle and quantify its thickness. X-ray analysis was used to detect elements associated with the anterior, central, and posterior portions of the lenses and their relative distribution. RESULTS: A distinctive morphological pellicle ranging from 0.1 to 8.6 microns was present on 12 of the 14 lenses. The pellicle was thicker on the Group 4 lenses than on the Group 1 lenses (P < 0.003). However, the pellicle on Group 1 lenses became thicker with increasing lens age (P < 0.02), but not as thick as on Group 4 lenses. Morphologically distinct lipid or jelly bump deposits were observed at the surface of both lenses from a single patient wearing 2 week old Group 4 lenses. Eleven lenses had sulfur-bearing tear components on the anterior zone. Sulfur was deposited within the matrix of nine lenses. The sulfur containing moieties were more prevalent on Group 4 lenses (P < 0.002). More sulfur was assayed on older lenses (P < 0.004). The anterior lens zone had more sulfur-bearing tear components than did the posterior or center zones (P < 0.05). CONCLUSIONS: The physiologically normal pellicle is a distinct morphological entity covering the anterior lens surface. Abnormal deposits such as the discrete microgel region, known as jelly bumps, are not part of the physiologically normal pellicle at the anterior lens surface and have the potential to induce pathology. Sulfur-containing moieties within the matrix may represent the breakdown of large proteins and mucoproteins or intact proteins, as well as contaminants such as cosmetics and environmental pollutants. It is also possible that entire small proteins, such as lysozyme, impregnate the matrix. The moieties that become entrapped within the matrix or rigidly adhere to the matrix should be considered true deposits.

Bacterial assay of contact lens wearers.

PURPOSE: The goal of the project was to determine the quantity of bacteria on the contact lens and adjacent areas of the eye. This paper is a quantitative study of the contact lens and ocular aerobic microbiota in a mixed group of daily and extended wear disposable contact lens users. METHODS: The contact lens, the lower fornix, tears collecting at the lower fornix, and edge of the lower lid at the Meibomian gland margin were assayed for the quantity of bacterial colony forming units (CFU). Eighteen patients wearing 49 disposable high water content hydrogel contact lenses were assayed and the mean lens age was 8.8 +/- 4.6 days. Three patients wore their lenses on a daily wear basis and 15 on an extended wear schedule. Tear samples were obtained with sterile microbial loops and the lens was macerated into small particles with a tissue grinder. The samples were poured onto the surface of chocolate agar plates and incubated at 35 degrees C for 48 h in 5% Co2. RESULTS: The lid margin revealed the greatest bacterial presence (mean = 9.7 CFU; median = 2 CFU; mode = 0 CFU). The lens showed the next greatest presence of CFU (mean = 4.5 CFU; median = 1 CFU; mode = 0). The fornix and tears revealed the least bacterial presence (fornix: mean = 2.6 CFU; median = 0 CFU; mode = 0 CFU). The bacteria were coagulase-negative staphylococci. CONCLUSIONS: The bacterial assay of disposable lens wearing contact lens subjects indicates that the lid margins are the greatest source of bacteria with the tears being the lowest. These studies support the concept that in the eye, the lens typically does not possess a large number of bacteria under normal conditions.

Childhood Guillain-Barré syndrome in Paraguay, 1990 to 1991.

During 1990 to 1991, through a national surveillance program for poliomyelitis, the Paraguayan Ministry of Health received reports of 50 children with incident acute flaccid paralysis (< 15 years old). On the basis of established criteria, 37 were diagnosed with Guillain-Barré syndrome. The average annual incidence rate for 1990 to 1991 was 1.1/100,000 children. The clinical course was more benign than reported in other pediatric series. There were low rates of hospitalization (57%), respiratory compromise (8%), and intubation (5%). The overall severity, however, was similar to that described in previous reports, with a 3% case-fatality rate and an 81% total recovery rate at 12 months. Seventy-six percent of patients had symptom onset during January to April, the warmest months of the year. Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barré syndrome. There was no correlation between occurrence of Guillain-Barré syndrome and prior immunization.

How to produce moisture chamber eyeglasses for the dry eye patient.

BACKGROUND: Moisture chambers are prosthetic devices coupled to eyeglasses that slow the evaporation of the tears from the ocular surface. The need for moisture chamber glasses is most evident when a patient suffers from Sjögren's syndrome. This disease creates a pathologically dry eye from tear anomalies. Other ocular and systemic conditions can also cause a painfully dry eye. METHODS: The concept behind a moisture chamber is to significantly minimize the air flow over the ocular surface. The chamber provides a vapor barrier that functions passively to prevent tear evaporation. This is achieved by using a polyurethane plastic to produce a chamber contiguous with spectacles. RESULTS: The chamber provides a humid environment behind the eyeglass lens and in front of the eye surface. Before deciding to produce a moisture chamber, one should consider the extensive time consumption involved in the production of these facially contoured customized devices. CONCLUSIONS: It may take 3-6 hours for a technician who has not previously made a moisture chamber to construct the first one. As the proficiency increases, one may be able to streamline the process to approximately 3 hours. This approach was investigated because of the paucity of available information about the production of moisture chamber glasses and the acute need and benefit by pathological dry eye patients for these special glasses.

Surface analysis of hydrogel contact lenses by ESCA.

We used electron spectroscopy for chemical analysis (ESCA) to examine the surface chemistry of polymacon, tefilcon, and bufilcon hydrogel contact lenses. Worn and unworn water-cleaned and surfactant-cleaned lenses were compared. The surface chemistry of unworn lenses, which were used as controls, consisted of approximately 70% carbon, 25% oxygen, and < 10% other elements (i.e., silicon, sulfur, sodium, nitrogen, and zinc). In general, surfactant cleaning removed silicon contamination, but left a residue containing sulfur and zinc. The increase in the nitrogen/carbon (N/C) ratio for worn bufilcon and polymacon lenses was significantly greater than the N/C ratio for unworn bufilcon and polymacon lenses. As a group the worn ionic lenses (bufilcon) showed a greater N/C ratio than the worn nonionic lenses (polymacon, tefilcon). The nitrogen that appears on all worn lenses probably represents adherent as well as adsorbed surface proteins. The highest N/C ratios were found on a pair of pathologically deposited lenses and on the lens with the longest wearing time (2 years). For the bufilcon and polymacon lenses, the differences observed in the ESCA data for the unworn and worn lenses suggest that contact lenses begin interacting with the tear film within 1 minute (the shortest wearing time in this study).

Microbial contamination of hydrophilic contact lenses: quantitation and identification of microorganisms associated with contact lenses while on the eye.

Previous studies have demonstrated the presence of microorganisms on hydrogel contact lenses under various usage conditions. We conducted this study to quantify and identify viable bacteria and fungi associated with hydrogel contact lenses while on the eye. We removed the lenses from patients' eyes using aseptic techniques and cultured them to identify loosely adherent, as well as lens bound, microorganisms. Lenses were vortexed in a transfer medium (thereafter called the lens extract) and the lenses were then incubated in an agar sandwich separately from the transfer medium. We cultured 108 lenses (82 daily wear and 26 extended wear) from 49 patients. Bacteria were cultured from 38% (41) of the lenses; for 31 of these 41 lenses bacteria were isolated only from the lens extracts (made by vortexing lenses in a transfer medium), suggesting a transient association with the lenses. No fungi were isolated. Counts of less than 10 colony forming units (CFU)/lens were observed on 89% of the lenses. Staphylococcus epidermidis were the most frequently isolated bacteria. A statistically significant relation was observed between increased CFU/lens and increased lens age for extended wear lenses (p = 0.028).

Antibodies to the ganglioside GD1b in a patient with motor neuron disease and thyroid adenoma.

Patients with motor neuron disease with thyroid disorders have been described, although the relationship between the two conditions is unclear. We treated a patient with amyotrophic lateral sclerosis who also had a follicular adenoma of the thyroid gland. Because thyroid gland plasma membranes contain high concentrations of complex gangliosides, such as GD1b, and some patients with motor neuron disease have IgM antibodies to GD1b, we decided to assay serum from this patient for the presence of antiganglioside antibodies. IgM antibodies to GD1b were detectable at serum dilutions of 1:500 and 1:1000 by enzyme-linked immunosorbent assay. While these titers are less than those usually described in patients with plasma cell dyscrasia, they are well in excess of normal values. Antibody to GM1 was also detectable at a lower (1:100) dilution. We do not know the importance of the anti-GD1b antibodies in this patient, but it is possible that antibodies to GD1b are involved in this and other cases of motor neuron disease associated with thyroid disease.

A Bootstrap Confidence Interval Based on a Correlation Corrected for Range Restriction.

The sample correlation coefficient corrected for range restriction was bootstrapped to obtain a confidence interval on the unrestricted population correlation, rho. The technique was evaluated using a computer simulation under different values of rho and four distributions (normal, mixed, positively skewed and negatively skewed). The corrected correlation coefficient yielded accurate bootstrap intervals over the four distributions. On the average, the size of rho did not affect the accuracy of the confidence interval. However, it did affect stability. The interval behaved rather erratically when rho was small (.1) and sample size was small. Sample size was found to be the most important factor in determining accuracy and stability. Overall, the results suggest that bootstrapping the corrected correlation coefficient is a reliable method for obtaining a confidence interval on rho especially when the sample size is moderate to large (n > 50).

Contact lens induced giant papillary conjunctivitis: a retrospective study.

In this retrospective epidemiological study, records from the Contact Lens Department of SUNY College of Optometry were randomly selected and reviewed. An association between contact lens induced giant papillary conjunctivitis (GPC) and a FDA classified sub-category was found. Younger patients were shown to have a higher risk of developing GPC. Gender and tear film break-up time were not found to be associated with the condition. The mean replacement time for hydrogels was 10.8 +/- 9.2 months with no significant differences among contact lens polymer types. The GPC phenomenon was almost exclusively bilateral with a mean onset time of 31.4 months after commencing lens wear. A model for the development of GPC based on tear film interactions with the hydrogel lens surface is presented. A model for the tear film's interaction with the hydrogel contact lens in situ is offered.

Surface interactions on hydrogel contact lenses: scanning electron microscopy (SEM).

SEM was used to visualize tear-film/hydrogel polymer surface interactions. Lenses were preserved by fixation including a quaternary ammonium complex to aid in mucin preservation. In less than 2 weeks of continuous wear the anterior surface was completely coated, yet the coating was absent from the posterior lens surface. Tear-film break-up over the deposited lens surface, combined with degradation and deformation at the polymer surface boundary, as well as entrapment of moieties within the polymer matrix, all occurred. These are the likely culprits which can contribute to adverse reactions as well as cause light scatter and diminished vision. Lenses removed directly from the eyes of patients suffering with different forms of conjunctivitis were obtained. Bacterial and viral conjunctivitis can induce a microbially contaminated as well as a heavily deformed and deposited lens. Viable and intact microbes were not typically observed in the mucoprotein layer of hydrogel contact lenses.

Spoilage of hydrogel contact lenses by lipid deposits. Tear-film potassium depression, fat, protein, and alcohol consumption.

"Jelly-bump" deposits, which are composed mainly of lipids, on high water content, extended-wear hydrogel lenses, are a clinically significant problem of unknown etiology. The authors explored the effect of nutrition on the frequency of deposition of these jelly bumps. Forty-three patients were included in this masked case-control study from five contact lens practices in North America. Thirty patients were lipid-depositor cases and 13 were controls. Tear specimens were drawn and analyzed for potassium by atomic-absorption spectrophotometry. Detailed dietary histories were conducted and diet nutrient composition was computed. Patients with diminished tear-potassium concentrations have an increased risk of jelly-bump deposition. Elevated intake of protein, alcohol, and cholesterol also appeared to be correlated significantly with increased jelly-bump deposition. The authors found that diabetics and the use of diuretics, anticholinergics, sympathomimetics, were associated with tear-film potassium depletion and lipid deposit formation.

Surface interactions on hydrogel extended wear contact lenses: microflora and microfauna.

The microbial flora and fauna of 25 high water content nonionic "soft" contact lenses worn by patients on an extended wear basis, 4 hand-cleaned patient-worn lenses, and 4 improperly maintained lenses were compared. Almost all the patient-worn lenses (24 of 25) were free of viable microorganisms, whereas all the hand-cleaned lenses (4 of 4) were contaminated with different microorganisms. This study showed that hand contact is a major source of microbial contamination of a lens and that usually the hand-transported microorganisms do not survive permanently on the lens in a healthy, normal eye. Improperly maintained lenses demonstrated pathogenic microbial associations. Proof of the eye's potent antimicrobial environment was demonstrated. Thus, microorganism-lens associations are largely due to lens handling and inappropriate maintenance regimens. Typically there are few microorganisms on an extended wear soft lens while it is being worn.

Origin and composition of lipid deposits on soft contact lenses.

"Jelly bump" deposits, common to high-water-content hydrogel extended-wear contact lenses, were shown to be composed primarily of lipids, with calcium an optional minor component. Extraction, separation, and analysis of deposited versus nondeposited regions of the same lenses reveals that lipids were restricted to the deposited regions of the lens, with a composition of long and intermediate chain cholesterol esters (possibly waxy esters) and triglycerides. This composition is independent of deposit size or individual depositor. Except for an elevated triglyceride level, the composition mirrors that of the tear lipid layer. Analysis of tear films of heavy and nondepositors, combined with clinical evidence, reveals that many depositors have a relatively decreased tear flow with some exhibiting an elevated tear-lipid fraction. A mechanism of deposition is proposed to require the local depletion of the aqueous tear layer stranding lipid on the lens surface, thereby creating a hydrophobic region suitable for further deposition. Deposition does not mechanistically involve tear film proteins, calcium, or microorganisms although they can, at times, be associated with the lipid deposit.