Comparative LC-MS/MS and HPLC-UV Analyses of Meropenem and Piperacillin in Critically Ill Patients.

BACKGROUND: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics has become a valuable tool to guide dosing in critically ill patients. The main goal of the study was to compare two routinely used techniques for beta-lactam TDM in intensive care unit (ICU) patient samples, namely isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) and high-performance liquid chromatography combined with ultra-violet detection (HPLC-UV). METHODS: A set of 80 sera/plasma samples from ICU patients receiving therapeutic meropenem or piperacillin dosage was investigated. Sample duplicates and quality assessment samples were assayed in parallel with an in-house LC-MS/MS and a commercially available IVD HPLC-UV kit. A pharmacokinetic and pharmacodynamic (PK/PD) target with ≥ 22.5 mg/L for piperacillin and ≥ 8.0 mg/L for meropenem was used for medical assessment of trough sample (n = 40) antibiotic concentrations. RESULTS: There was no difference between serum and Li-heparin plasmas. Concentration deviations were found for 4% of meropenem and 17% of piperacillin samples. Eliminating the influence of the systemic bias of approximately 10% for piperacillin, measurement discrepancies ≥ 25% between LC-MS/MS and HPLC-UV analyses were only observed for ≈ 4 - 6% of all samples. In the same way, identical PK/PD target attainment rates of 50 - 60% could be obtained. CONCLUSIONS: After correction of the analytical bias for piperacillin measurements, both methods showed comparable results, also with respect to clinical decision limits. HPLC-UV analysis is an adequate TDM methodology for testing of beta-lactam antibiotics in centers where no special knowledge in LC-MS/MS based TDM is present. However, potential matrix effects, interferences, and calibration issues for both methods must be taken into account.

Effects of the Glaucoma Drugs Latanoprost and Brimonidine on Corneal Temperature.

PURPOSE: The aim of this study was to investigate the effects of the glaucoma drugs latanoprost, brimonidine, and the combination of both on the central corneal temperature (CT) of healthy subjects by means of infrared thermography. Changes of the central CT may reflect changes of ocular blood flow. METHODS: Before application and during 2 hours after the application of latanoprost, brimonidine, or the combination of both in one eye, the CT in both eyes of 40 healthy subjects was measured repeatedly. RESULTS: Brimonidine reduced CT by approximately 0.5°C. This effect was statistically significant (P < 0.0001). Latanoprost, however, had a very small and insignificant influence (P = 0.47). Accordingly, the combination of brimonidine and latanoprost also reduced CT up to 0.5°C, and this effect was statistically significant (P < 0.0001). CONCLUSIONS: Brimonidine, but not latanoprost, had a significant effect on central CT. This cooling effect of brimonidine is most probably due to a drug-induced reduction of blood circulation in the ciliary body and iris and to a certain extent also to a reduction of blood flow in the fundus of the eye. TRANSLATIONAL RELEVANCE: This study shows evidence that thermography of the cornea provides indirect information on the influence of drugs on the blood flow to the anterior segment of the patient's eye.

Cornea Thermography: Optimal Evaluation of the Outcome and the Resulting Reproducibility.

PURPOSE: The aim of the study was to establish a standardized quantitative evaluation of corneal temperature (CT) that includes anchoring reference points in the topography and minimization of artifacts. We further investigated the distribution and the short- and long-term reproducibility of the CT values, as well as the influence of the core temperatures. METHODS: The CT values in both eyes of 40 healthy subjects were measured through thermography. These examinations took place over the course of four visits within 2 consecutive weeks. At each visit, the CTs were measured twice in both eyes with intervals of 15 minutes between measurements. RESULTS: CT values were not significantly different between the right and left eyes and their distribution was nearly normal. The CTs increased slightly when measured twice over the 15-minute intervals (short-term reproducibility) but remained stable over a period of 2 weeks (long-term reproducibility). In addition, the CT values depended on the core temperatures. CONCLUSIONS: Ocular surface thermography is a fast and noninvasive examination. The methods of optimized and standardized evaluation of the CT values facilitate comparisons and follow-ups. TRANSLATIONAL RELEVANCE: Thermography can be used clinically and scientifically only if both the measurement and its evaluation are efficient and standardized and if the outcomes are highly reproducible.

Relationship between normal tension glaucoma and Flammer syndrome.

BACKGROUND: Besides intraocular pressure, vascular factors play a role in the pathogenesis of glaucomatous optic neuropathy. One of these potential vascular factors is Flammer syndrome. The purpose of the present study was to determine in a Korean population whether signs and symptoms of Flammer syndrome occur more often in normal tension glaucoma patients than in control subjects. METHODS: Two hundred forty-six normal tension glaucoma patients and 1116 control subjects responded to a multiple-choice questionnaire asking about 15 signs and symptoms of Flammer syndrome. RESULTS: Seven of the 15 signs and symptoms of Flammer syndrome (increased drug sensitivity, good smell perception, reversible skin blotches, tinnitus, long sleep onset time, tendency to perfectionism, and cold hands/feet) were significantly more often positive in normal tension glaucoma patients than in controls. Six additional signs and symptoms (migraines, low blood pressure, headaches, dizziness, increased pain sensation, and feeling cold) also occurred more often, but did not reach statistical significance. Only two items (low body weight and reduced feeling of thirst) were more frequently (not significant) positive in the controls. CONCLUSION: There is an association between normal tension glaucoma and Flammer syndrome. If future studies confirm this relationship, treatment of Flammer syndrome may help to prevent normal tension glaucoma or to slow down its progression.

Multiple sclerosis and primary vascular dysregulation (Flammer syndrome).

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS of still unknown aetiology. Flammer syndrome (FS) encompasses a set of symptoms and signs that are primarily but not solely related to the dysregulation of blood vessels. The purpose of the present study was to determine whether FS symptoms occur more often in MS patients than in controls. METHODS: Fifty-eight MS patients and 259 controls answered a questionnaire covering 15 symptoms and signs of FS. RESULTS: Six of the 15 symptoms and signs of FS (dizziness, low body mass index, cold hands and/or feet, tendency toward perfectionism, reduced thirst, feeling cold) were found significantly more often in MS patients than in controls. Seven additional symptoms and signs (tinnitus, headaches, increased pain sensation, long sleep-onset time, migraines, increased response to certain drugs, low blood pressure) also occurred more often in MS patients, but the difference in frequency was not statistically significant. One sign (reversible skin blotches) was found less often in MS patients, but the difference in frequency was not statistically significant. One symptom (increased smell perception) was found significantly less often in MS patients. CONCLUSIONS: MS patients suffer significantly more often from FS symptoms and signs than controls. The reason for this association between MS and FS and the potential implications of this association still need to be determined.