Endothelin-1 levels and biomarkers of oxidative stress in glaucoma patients.

To investigate the levels of endothelin-1 (ET-1), homocysteine (Hcy), vitamins A, E, B12 and folic acid in plasma of patients with different types of glaucoma: primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). Patients were classified into 3 groups: group POAG comprised 48 patients, group NTG comprised 15 patients, and control group that comprised 75 healthy subjects. ET-1 levels were measured by ELISA, Vitamins A and E by HPLC, and Vitamin B12, homocysteine, and folic acid levels were determined by chemiluminescent immunoassay. The ET-1 and Hcy levels were significantly higher (p = 0.002) in the POAG group compared to NTG and control group. Vitamin E levels were significantly lower (p = 0.001) in the NTG group compared to POAG and control group. The increase of Hcy and ET-1 in POAG patients is related to vascular endothelial dysfunction. Thus results may play a key role in the development of this disease. Lower levels of Vitamin E in the NTG group suggest that oxidative process plays an early role in the development of this type of glaucoma.

Paediatric life support instructors courses in Spain. Spanish Paediatric and Neonatal Resuscitation Group.

Between October 1996 and February 1998 we have provided five PLS instructors courses for 127 physicians. The instructor course takes 20-24 h over in 3 days, with 20-36 students per course. Theory classes last 5 h and practical stations between 14 and 18 h. Theory classes include: types and organisation of paediatric courses, resuscitation material, methodology of education, didactic methods, and methods of evaluation. The practical classes include techniques of oral expression, resuscitation material, and methodology, and evaluation of basic life support, airway and ventilation, venous and intraosseous access, diagnosis and treatment of arrythmias, neonatal resuscitation and advanced resuscitation. At the end of the course the students perform an anonymous written evaluation of the course with scores between 1 (very bad), 2, 3, 4 and 5 (very good). Theoretical aspects practical classes, methodology, and organisation of the PLS instructors courses are considered satisfactory by the students. We conclude that PLS instructors courses are important for assuring the uniformity and quality of paediatric life support courses.

Expanded gentamicin volume of distribution in critically ill adult patients receiving total parenteral nutrition.

Aminoglycoside antibiotics distribute into the extracellular fluid compartment and are eliminated by the kidney via glomerular filtration. Malnutrition and total parenteral nutrition influence the fluid and electrolyte status of the patient, and cause organ changes. The purpose of this clinical study was to characterize the kinetic behaviour of gentamicin in the parenterally fed critically ill adult patient. Eighty-six critically ill adult patients treated with gentamicin for severe Gram-negative infections were enrolled in the study (mean +/- SD): age, 60 +/- 14 years; weight, 69.4 +/- 10.2 kg; height, 163 +/- 10 cm; 22 females and 64 males. Four study groups were defined (2 x 2): total parenteral nutrition vs. fluid therapy, and acute renal failure vs. normal renal function. The drug was administered by intermittent intravenous infusion. Blood samples were drawn at steady-state, 5 min before the next dose ('trough') and 30 min after the termination of the infusion ('peak'). Gentamicin serum concentration was determined by fluorescence polarization immunoassay. Gentamicin pharmacokinetic parameters were estimated by non-linear regression analysis, assuming a one-compartment model and first-order elimination from the central compartment. Treatment of malnutrition with total parenteral nutrition increased gentamicin volume of distribution (P < 0.001), but did not affect total body clearance (P = 0.75). This change tended to produce lower peak concentrations (< 4 micrograms/ml, P = 0.07), thus potentially compromising therapeutic effectiveness. There was no significant influence on trough concentrations (P = 0.56). Patients receiving fluid therapy had a volume of distribution of 0.34 +/- 0.08 litre/kg, while those fed by the intravenous route showed larger values (0.43 +/- 0.12 litre/kg), irrespective of their renal function. This may be explained by the extracellular water expansion caused by stress, malnutrition, and parenteral refeeding. Gentamicin dosage regimens in critically ill adult patients on total parenteral nutrition should be formulated on the basis of larger volumes of distribution and to attain therapeutic serum concentrations higher doses may be required.

Critically-ill patients receiving total parenteral nutrition show altered amikacin pharmacokinetics.

The purpose of this clinical study was to characterise the kinetic behavior of amikacin in the parenterally-fed critically-ill adult patient. 22 critically-ill adult patients treated with amikacin (15.5 +/- 7.9 mg/kg/day) for severe gram-negative infections were enrolled into a non-randomised control trial. Malnourished patients were administered total parenteral nutrition (TPN, n = 11), while well-nourished patients received fluid therapy (FT, n = 11). Amikacin pharmacokinetic parameters were estimated by non-linear regression analysis, assuming a one-compartment model and central first-order elimination. Patients receiving TPN showed an expanded amikacin distribution volume (0.403 +/- 0.0961/kg vs. FT 0.298 +/- 0.083 l/kg, p < 0.05), and a tendency towards increased total body clearance (0.089 +/- 0.029 l/kg/h vs. FT 0.069 +/- 0.0201/kg/h, p = 0.09). TPN produced lower peak concentrations (19.3 +/- 3.1 mcg/ml vs. 23.1 +/- 3.5 mcg/ml, p < 0.05), but had no significant influence on trough concentrations (p = 0.56). Patients on TPN also showed increased body temperature (p < 0.05) and fluid intake (p < 0.05), and decreased hematocrit (p < 0.05). Stress, malnutrition, parenteral nutrition itself, fluid and osmotic overload, and fever often occur concurrently in parenterally-fed patients and appear to produce lower amikacin serum levels. Consequently, critically-ill patients receiving TPN need higher amikacin doses and individualised treatment by monitoring serum concentrations, to ensure optimal therapeutic response.