Settings and effectiveness of the revised probe compared to the original probe for micropulse transscleral cyclophotocoagulation.

PURPOSE: The goal of this study was to compare the settings and effectiveness of the original P3 and revised P3 probes for micropulse transscleral cyclophotocoagulation. METHODS: This retrospective cross sectional study includes a total of 56 patients with glaucoma who received micropulse transscleral cyclophotocoagulation. 32 patients received treatment with the original P3 probe and 24 received treatment with the revised P3 probe. Success was defined as a 20% reduction in intraocular pressure. Laser settings, pre-op and post-op intraocular pressures, and pre-op and post-op medications were assessed. RESULTS: A 20% IOP reduction was achieved in 50% of patients in the original probe vs. 58.3% in the revised probe at one month (P = 0.536) and 71.9% vs. 50% at three months (P = 0.094), respectively. The revised P3 probe used higher values of power (2500 mW vs. 2023 mW, P < 0.0001), total duration (217 s vs. 179 s, P < 0.0001), and energy (170 J vs. 113 J, P < 0.001). There was a significant decrease in IOP lowering meds with the original probe at one month (-0.9 +/- 1.5 vs. -0.0 +/- 0.7, P = 0.010), but this was not seen at three months. CONCLUSIONS: There is no significant difference in IOP lowering effect between probes despite the revised probe using higher total energy. The original probe may be associated with fewer medications at 1 month, but not at 3 months. Further studies with longer follow up are needed to optimize the treatment parameters in order to maximize effectiveness while limiting side effects.

Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome.

PURPOSE: To report an unusual presentation of commercial cannabidiol (CBD) oil-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS-TEN). METHODS: A 56-year-old woman presented with acute onset of a diffuse, blistering, maculopapular rash with over 30% total body surface area (BSA) involvement two days after taking CBD oil sublingually for chronic pain. Biopsy confirmed SJS-TEN. Ophthalmology was consulted and mild eye involvement was found. She was started on topical cyclosporine, prednisone, moxifloxacin, and erythromycin ointment to prevent progression, which was successful. She was otherwise treated with supportive therapy in the intensive care burn unit and ultimately passed away from septic shock. CONCLUSION: In this case, we described an unusual drug-induced SJS from a commercial, non-FDA-regulated cannabis product. The use of a commercial CBD product should be cautioned due to potential for series of drug reactions to the cannabis product and the risk for reaction to other unregulated other pharmacological components.

Blood glucose and coronary artery disease in nondiabetic patients.

OBJECTIVE: Nondiabetic patients were studied to determine whether modest elevations in blood glucose may be associated with a greater incidence of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Baseline morning blood glucose determinations were evaluated with respect to subsequent coronary disease using records from 24,160 nondiabetic patients. CAD was identified from myocardial infarction, new diagnoses of angina, or new prescriptions for nitroglycerin that occurred more than a year after baseline glucose determinations. RESULTS: Of 24,160 patients studied, 3,282 patients developed CAD over a total analysis time at risk of 77,048 years. Higher baseline morning glucose (100-126 vs. <100 mg/dl) was associated with a 53.9% greater myocardial infarction incidence rate, an 18.6% greater acute coronary syndrome incidence rate, and a 26.4% greater number of new prescriptions for nitrates (all P < 0.05). A Cox proportional hazards model with adjustment for age, BMI, sex, creatinine, lipids, smoking, and medications showed that elevated fasting glucose was associated with an increased hazard for new CAD (hazard ratio 1.13 [95% CI 1.05-1.21], glucose >100 vs. <100 mg/dl). Kaplan-Meier analysis showed that elevated baseline glucose was associated with a progressive increase risk of CAD with time. CONCLUSIONS: Patients with higher baseline blood glucose levels in the absence of diabetes and after adjustment for covariants have a significantly greater risk for development of CAD.

Effect of dexrazoxane on doxorubicin pharmacokinetics in young and old rats.

PURPOSE: Although dexrazoxane (ICRF-187) is used clinically to protect against doxorubicin cardiotoxicity, the age-related effect of dexrazoxane on doxorubicin pharmacokinetics has not been well studied. METHODS: We therefore examined the effect of pretreatment with dexrazoxane (50 mg kg(-1) i.p. 1 h prior to administration of doxorubicin 2 mg kg(-1) i.v. bolus) on doxorubicin and doxorubicinol pharmacokinetics in Fischer 344 rats at 5 months of age (young adult) and 22 months of age (old). RESULTS: Dexrazoxane had no major effects on doxorubicin or doxorubicinol pharmacokinetics in plasma or heart in either young or old rats. However, age had significant effects on anthracycline pharmacokinetics. Early plasma concentrations were increased and systemic clearance of doxorubicin was decreased in old compared with young rats. Cardiac concentrations of doxorubicin (AUC) were significantly increased in old rats. In addition cardiac doxorubicinol concentrations (AUC 0-72 h) were increased by over 80% in old compared to young rats. CONCLUSION: The results suggest that dexrazoxane does not alter doxorubicin pharmacokinetics. In contrast, aging in the rat model is associated with altered doxorubicin and doxorubicinol pharmacokinetics, in particular in the heart. These changes could increase the risk of anthracycline cardiotoxicity with age.

Arginine to lysine 108 substitution in recombinant CYP1A2 abolishes methoxyresorufin metabolism in lymphoblastoid cells.

1. Cytochrome P4501A2 (CYP1A2) activates a large number of procarcinogens to carcinogens. Phytochemicals such as flavones can inhibit CYP1A2 activity competitively, and hydroxylated derivatives of flavone (galangin) may be potent, selective inhibitors of CYP1A2 activity relative to CYP1A1 activity. Molecular modelling of the CYP1A2 interaction with hydroxylated derivatives of flavone suggests that a number of hydrophobic residues of the substrate-binding domain engage in hydrogen bonding with such inhibitors. 2. We have tested this model using site-directed mutagenesis of these residues in expression plasmids transfected into the human B-lymphoblastoid cell line, AHH-1 TK+/-. 3. Consistent with the molecular model's predicted placement in the active site, amino acid substitutions at the predicted residues abolished CYP1A2 enzymatic activity. 4. Transfected cell lines contained equal amounts of immunoreactive CYP1A2. 5. Our results support the molecular model's prediction of the critical amino acid residues present in the hydrophobic active site, residues that can hydrogen bond with CYP1A2 inhibitors and modify substrate binding and/or turnover.