Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice.

The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8(+) T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.

Anaesthetic management and outcomes in patients with surgically corrected D-transposition of the great arteries undergoing non-cardiac surgery.

BACKGROUND: Patients with effective repair of D-transposition of the great arteries (D-TGA) increasingly present for non-cardiac surgery. These patients may be predisposed to heart failure, arrhythmias, and sudden death, especially after the atrial switch repair. This retrospective study was undertaken to review the care and outcomes of patients with D-TGA who presented for non-cardiac surgery. METHODS: Records for patients with surgically corrected D-TGA undergoing general anaesthesia for non-cardiac surgery between October 2000 and April 2008 were reviewed. The anaesthesiology records, operative note, admission history and physical examination records, and discharge summaries of these patients were reviewed and the following data collected: patient characteristics; comorbidities; surgical procedure; anaesthetic and monitoring techniques; intra- and postoperative complications; and admission status. RESULTS: Fifty procedures, including 43 in the paediatric setting and seven in the adult setting, comprised the final sample. The majority of these patients received anaesthesia on an outpatient basis in the paediatric hospital, without invasive monitoring and without complication. There were four adverse events including a significant bradycardia, failed extubation after two of the procedures, and postoperative bleeding requiring return to the operating theatre in another. CONCLUSIONS: Data suggest that the majority of patients with surgically corrected D-TGA can safely undergo general anaesthesia, often as outpatients, with no invasive monitoring. However, given the incidence of adverse events, it remains imperative that the perioperative care be individualized based on the presence of comorbidities, type of repair, residual cardiac disease, severity of planned surgery, and experience of the provider.

Suppression of adrenergic adaptation in the eye with a prostaglandin synthesis inhibitor.

The treatment of glaucoma patients with a topical medication is sometimes associated with adaptation (the development of subsensitivity) to the effect of the medication. In the rabbit eye, adaptation develops when norepinephrine is administered topically on a daily basis. A marked decrease in the intraocular pressure is observed the first day, but diminishing responses are observed on subsequent days. Since prostaglandins may be released in response to catecholamines and have been found to inhibit adrenergic neurotransmission, we treated rabbits with topical flurbiprofen, a potent cyclooxygenase (prostaglandin synthesis) inhibitor, to suppress adaptation to norepinephrine. The results demonstrate a significant suppression of adaptation in the concentration range of 0.001% flurbiprofen (p less then 0.0005). This finding supports the theory that cyclooxygenase products mediate the development of adaptation to exogenous norepinephrine in the rabbit eye.

Orbital abscess.

A staphylococcal orbital abscess developed in a 55-year-old diabetic woman. Initial antibiotic therapy was apparently incomplete and resulted in an unusual clinical manifestation for an orbital infection. These unusual features included an insidious course of monocular visual loss and proptosis in the absence of fever, substantial orbital pain, and evidence of sinus disease; pancytopenia rather than leukocytosis was present. Surgical drainage followed by intravenous and oral antibiotic therapy resulted in marked clinical improvement, including a partial return of visual acuity. In the patient, however, a staphylococcal osteomyelitis of the shoulder and subsequent fatal septicemia developed several months later. Orbital infection continues to be a life-threatening condition, especially in debilitated patients.

Acute angle-closure glaucoma associated with surgical anesthesia.

We reviewed the records of all inpatients of the UCLA Medical Center from 1955 to 1980 with the discharge diagnosis of "glaucoma." Nine cases of acute angle-closure glaucoma occurring after spinal or general anesthesia were identified among the 913 records reviewed. Of the nine cases, two were bilateral. Seven patients were female and two were male; the mean age was 63 years. Six of the nine surgical procedures were extraperitoneal and abdominal or pelvic. Parenteral atropine sulfate or scopolamine hydrobromide was administered to seven patients and ephedrine sulfate to four; drug-induced mydriasis may have contributed to this complication. Succinylcholine chloride, which causes contraction of the extraocular muscles, was administered to six patients. Additionally, psychological stress in the surgical patient may increase the risk of this disease by causing mydriasis. Our cases are compared with previous reports.

The effects of Nd:YAG laser iridotomy on the corneal endothelium.

We studied 18 eyes of 18 patients undergoing Nd:YAG laser peripheral iridotomy for occludable anterior chamber angles. A Q-switched laser was used for all treatments. Preoperative and postoperative pachymetry and corneal endothelial cell counts were obtained centrally, in the nontreated superonasal quadrant, and in the treated superotemporal quadrant. No significant differences were found between preoperative and postoperative corneal thickness at any site. A small decrease in endothelial cell count (95 cells/mm2) at the treated site was statistically significant (P = .04).

A clinical evaluation of the BioPen.

We conducted a clinical trial on the Oculab BioPen, a portable, handheld applanation instrument designed to measure ocular axial lengths. We compared the measurements obtained from the BioPen with those obtained from the Ultrascan Digital B System IV from CooperVision. Accuracy and reproducibility were assessed in vitro by performing ten measurements with each instrument on a precalibrated 25.8-mm plastic test block. The in vivo reproducibility of the BioPen was evaluated by performing five serial readings on each eye of 58 patients. Keratometry measurements were also recorded to determine whether the BioPen provided consistent readings regardless of corneal curvature. We found the BioPen to be as accurate and reproducible as the Ultrascan Digital B in vitro and in vivo. Corneal curvature had no effect on the in vivo reproducibility of the BioPen.

Effects of argon laser iridotomy on the corneal endothelium.

We studied 14 eyes of 14 patients undergoing argon laser peripheral iridotomy for occludable (narrow) anterior chamber angles. Preoperative and postoperative pachymetry and corneal endothelial cell counts by specular microscopy were obtained centrally and in both the treated and nontreated superior quadrants. No significant differences were found between preoperative and postoperative measurements of corneal thickness and endothelial cell counts in any area.

Biometric variables in patients with occludable anterior chamber angles.

Biometric studies of the ocular dimensions in eyes with narrow anterior chamber angles provide insight into the pathophysiology of pupillary block and may show which eyes are more prone to develop angle-closure glaucoma. We reviewed the records of 56 patients with occludable angles examined between 1980 and 1984. Initial biometric data obtained on the patients included corneal diameter, anterior chamber depth, lens thickness, and ocular axial length. The average length of follow-up was five years. Of 54 patients with complete clinical records, 20 (37%) eventually required peripheral iridectomy after a mean duration of 16 months from the initial examination. Cox's survival analysis showed a strong correlation between shortened duration to peripheral iridectomy and increasing lens thickness/ocular axial length ratio factor (P = .03). No other variables were significantly related to outcome. This suggests that the lens thickness/ocular axial length ratio may be useful as a predictor of clinical outcome in narrow-angle glaucoma.

Inhibition of the epinephrine-induced reduction of intraocular pressure by systemic indomethacin in humans.

In a prospective, randomized, double-masked study, 2% epinephrine applied topically twice each day for two weeks to the eyes of patients with glaucoma or ocular hypertension caused an 8.1 +/- 1.4-mm Hg (mean +/- S.E.M.) reduction of intraocular pressure in placebo-treated patients, but only a 1.9 +/- 0.6-mm Hg decrease in patients treated with 25 mg of orally administered indomethacin four times each day (P less than .0005). Systemic treatment with indomethacin for one week did not significantly increase intraocular pressure by itself (baseline, 19.7 +/- 0.6 mm Hg, vs 20.1 +/- 1.4 mm Hg after indomethacin treatment). When indomethacin treatment was discontinued in those patients receiving topical epinephrine, there was a further significant (P less than .05) reduction in intraocular pressure compared with the placebo-treated group. Since the ocular hypotensive effect of topically applied epinephrine is inhibited by indomethacin, a cyclo-oxygenase inhibitor, these results suggest that this reduction of intraocular pressure is at least partially mediated by the endogenous production of prostaglandins, or other cyclo-oxygenase products, and that the intraocular pressure of glaucoma patients undergoing epinephrine therapy may increase when systemic cyclo-oxygenase inhibitors such as indomethacin or aspirin are taken.

Glaucoma in patients with uveitis.

The records of 100 patients (161 eyes) with uveitis were reviewed retrospectively to determine the prevalence of increased intraocular pressure, the forms of uveitis most commonly associated with glaucoma, and the forms that require specific glaucoma therapy. Secondary glaucoma was present in 23 patients (31 eyes): three of 24 patients with acute uveitis (three eyes, 12% of acute uveitis patients) and 20 of 76 patients with chronic uveitis (28 eyes, 26% of chronic uveitis patients). Eighteen patients (26 eyes, 78% of glaucoma patients) with chronic uveitis required long-term medical therapy to control intraocular pressure. Three patients (three eyes, 12% of glaucoma patients) with acute uveitis required short-term therapy to control intraocular pressure. The remaining two patients had transient increases in intraocular pressure that did not require treatment or that responded to treatment of intraocular inflammation alone. One patient with chronic uveitis (two eyes, 4% of glaucoma patients) required filtering surgery. At least five patients (eight eyes, 22% of glaucoma patients) had glaucomatous visual field defects. The results of this survey are consistent with the concept that secondary glaucoma is a management problem in patients with anterior segment inflammation and chronic rather than acute uveitis. An algorithm for the management of increased intraocular pressure in patients with uveitis is proposed.

Daily boron intake from the American diet.

Interest in boron as a naturally occurring trace element nutrient from the food supply is increasing. Mounting evidence suggests that boron is essential to human beings. This study explores the major food and beverage contributors of boron and estimates of daily boron intake from the American diet. Previous estimates in the literature of dietary boron consumption are based on limited foods and population segments. In this study we provide a more comprehensive assessment of boron consumption by the US population. A boron nutrient database of 1,944 individual foods was developed. These foods represent 95.3% by weight of all foods consumed in the US Department of Agriculture 1989-1991 Continuing Survey of Food Intakes by Individuals (1989-1991 CSFII). The Boron Nutrient Database (version 1.0) was then linked to the 3-day food records of 11,009 respondents to the 1989-1991 CSFII to generate the average daily boron intake for each person. The weighted 5th percentile, median, mean, and 95th percentile boron intakes, respectively, are 0.43, 1.02, 1.17 and 2.42 mg/day for men; 0.33, 0.83, 0.96 and 1.94 mg/day for women; and 0.40, 0.86, 1.01 and 2.18 mg/day for pregnant women. For vegetarian adults, these intakes are 0.46, 1.30, 1.47 and 2.74 mg/day for men and 0.33, 1.00, 1.29 and 4.18 mg/day for women. The top 2 boron contributors, coffee and milk, are low in boron, yet they make up 12% of the total boron intake by virtue of the volume consumed. Among the top 50 boron contributors, peanut butter, wine, raisins, peanuts, and other nuts are high in boron. As more data become available on daily boron requirements, the results of this study may be used to assess whether Americans' daily intake of boron is adequate.

The distribution of the antimicrobial protein, calprotectin, in normal oral keratinocytes.

Calprotectin is a heterodimeric peptide isolated from neutrophil cytosol that exhibits profound antimicrobial effects. Using monoclonal antibody MAC 387, calprotectin was found to be expressed in oral keratinocytes from normal, non-inflamed oral mucosa. Orthokeratinized sites including the attached gingiva and hard palate expressed low levels of calprotectin with a restricted pattern; immunoreactants were identified only within subcorneal keratinocytes. Parakeratinized mucosa from the lips, soft palate, tongue and buccal mucosa expressed calprotectin in a more widespread, yet variable pattern, immunoreactants being detectable in only a portion of the spinous layer in some cases whereas in others the pattern of expression was more topographically diffuse. Antigen was not detected in basilar and lower strata cells. Both cytoplasmic and nuclear decoration could be identified. The results indicate that oral mucosa harbours an antimicrobial deterrent to micro-organisms that may enhance the physical epithelial barrier of host defence.

Glomangiosarcoma with metastasis to the maxilla.

A thorough review of the literature disclosed very little information on glomangiosarcoma with no reported cases of verified metastases. We present a case which may be the first instance of oral metastatic glomangiosarcoma to be reported in the literature.

Soft-tissue examination in the dental office.

This article describes in detail all features of the head and neck soft-tissue examination as performed routinely in a dental office. The ongoing thought process while performing the exam is described, and examples of findings are given.

Sudden unexpected death in young athletes: a review.

Sudden death is a startling and tragic event that often sends ripples through our communities and even across our nation. Estimates have suggested that between 10 and 30% of adults die suddenly and unexpectedly and maybe 5% of these are related to sports. The purpose of this study is to examine the topic of sudden death in the young athlete through a review of several larger national studies. Then the etiology of these tragedies will be discussed. Finally, a review of the sudden death in adolescents and young adults in Alaska over the last 12 months will be presented.