Reticulocyte hemoglobin content allows early and reliable detection of functional iron deficiency in blood donors.

BACKGROUND: Frequent blood donations may lead to a depletion of body iron stores resulting in manifest anemia. Reticulocyte hemoglobin content (CHr) - a marker for impaired hemoglobinisation (IH) caused by functional iron deficiency (FID) - was investigated regarding its value as a routine screening parameter in frequent whole blood donors. METHODS: In a prospective study, 917 frequent blood donors and 688 first time or reactivated donors were tested for iron status and red blood cell count, including CHr. The ferritin index as a marker to indicate absent iron stores (AIS) was calculated. RESULTS: Depending on the number of donations during the preceding 12 months, AIS were detected in up to 21.4% of male and 27.8% of female donors, respectively. IH was present in up to 6.4% male and 16.7% female donors with 2 and 4 preceding donations, respectively. The defined CHr cut-off value was 28.0 pg to detect IH in frequent whole blood donors with AIS, leading to a test specificity of 98.2% (positive predictive value, PPV: 57.7%) in male and of 97.8% (PPV: 82.9%) in female donors. CONCLUSION: Determination of CHr is feasible to detect FID resulting in IH in frequent blood donors. It may help to prevent the development of anemia in frequent blood donors and also can help to decide whether donor deferral or even iron substitution need to be recommended.

Post-methionine-load hyperhomocysteinemia and increased lipoprotein(a) are associated with renal metabolic dysfunction: a hypothesis.

Previous studies have shown that homocysteine influences the structure of lipoprotein(a) [Lp(a)] and its affinity to fibrin, and that there is an increased risk of vascular disease when both homocysteine and Lp(a) are elevated. The aim of this study was to determine whether there is a correlation between increased total homocysteine (tHCY) and high Lp(a) concentrations, and whether increased concentrations of tHCY affect the concentration of unbound serum apolipoprotein(a) [Apo(a)]. Forty-seven male subjects recruited from a primary prevention screening program with normal serum creatinine and Lp(a) concentrations above 30 mg/dL were included and underwent a standardized oral methionine-loading test to increase the plasma tHCY concentration. This increase might lead to a modification of the Apo(a) structure, thus possibly influencing the serum concentration of unbound Apo(a). Fasting blood samples were taken before the tests and after 6 hours. The median values of tHCY increased about 4-fold after the methionine-loading test. Fasting tHCY did not show an association with Apo(a) and a post-methionine load increase of unbound Apo(a) was not observed. Backward multiple linear regression analysis, however, revealed that only post-load tHCY was independently and significantly influenced by Lp(a). Furthermore, Lp(a) correlated significantly with post-load tHCY, but not with fasting tHCY. Subdividing the subjects according to the Lp(a) concentration showed a significantly higher median concentration of tHCY after methionine load in subjects with Lp(a) over 50 mg/dL compared to subjects with Lp(a) under 50 mg/dL (P =.009). A similar cut-off was seen for post-load Apo(a) at 7.3 mg/dL (P =.04). Factors such as age, C677T-methylene-tetrahydrofolate-reductase (MTHFR) mutation, folate, vitamin B(12), and creatinine showed no significant influence on post-load tHCY in the different subgroups. The reasons for our findings remain partially unclear. However, considering our results and the current knowledge on the association of tHCY and Lp(a) concentration with the renal function, we hypothesize that both parameters may be linked by commencing renal metabolic dysfunction. It should be stressed that our hypothesis is speculative and that further studies will be necessary to improve the understanding of the interrelation of tHCY and Lp(a) concentration.

Plasma adrenaline concentrations during functional endoscopic sinus surgery.

OBJECTIVES/HYPOTHESIS: Vasoconstrictors (i.e., epinephrine) are routinely applied before functional endoscopic sinus surgery (FESS) but may have significant cardiac side effects. The controversy concerning clinical application of adrenaline is discussed. STUDY DESIGN: In a prospectively controlled study of 51 patients undergoing FESS we evaluated the absorption of adrenaline from standard cotton pledgets and submucous infiltration and the incidence of related side effects during surgery. Additionally, a control group of 12 patients undergoing tonsillectomy was investigated. METHODS: Plasma adrenaline concentrations were measured 1) before anesthesia, 2) after intubation, 3) after nasal packing with adrenaline soaked pledgets (adrenaline 1:1000) and submucous infiltration with 2 mL lidocaine with adrenaline 1:100,000 in each side, and 4) at end of surgery. The catecholamines were determined with a Merck-Hitachi Catecholamine Analyzer, model II (Merck, Darmstadt, Germany). Pulse, electrocardiogram (ECG), and blood pressure were monitored. RESULTS: In the FESS group, we found a remarkable decrease in systolic (S) as well as diastolic blood pressure (D) (P < .001), whereas the heart frequency was unaffected during surgery. All patients in the adrenaline group showed significant increase in plasma adrenaline (AD) concentrations in the third and fourth sample (P < .001). The control group, however, showed a significant rise in blood pressure only at beginning of surgery (P < .001) with cardiac pulse and plasma adrenaline concentrations unaffected by surgery or anesthesia. The often described severe side effects of adrenaline in combination with general anesthesia were not seen in any of our patients. CONCLUSIONS: Although systemic absorption of locally injected vasoconstrictors occurs, adrenaline-related side effects during FESS are extremely rare when the patient is monitored exactly.

Rapid, sensitive high-performance liquid chromatographic method for the determination of cyclosporin A and its metabolites M1, M17 and M21.

Cyclosporin A (CyA) and its metabolites seem to have nephro-, hepato- and neurotoxic side effects. Immunosuppressive therapy is a narrow path between the risk of rejection by underimmunosuppression and toxic organ damage by overdosage. Thus CyA dosage must be calculated to avoid the risks of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In routine monitoring of CyA therapy, it can be important to measure not only the parent drug but also the metabolites. We describe a rapid and isocratic high-performance liquid chromatographic method for measurement of CyA and its metabolites M1, M17 and M21 in whole blood. CyA was detected by ultraviolet absorption at 212 nm with a CN analytical column maintained at 50 degrees C and recycling of hexane-isopropanol as mobile phase for improved long-term column stability and efficiency. The minimum detectable concentration of CyA and the three metabolites was 10 ng/ml blood. Our modified HPLC method for the determination of CyA and its metabolites is a simple (isocratic), rapid (the retention times were 7.1 min for CYD, internal standard, 8.9 min for CyA, 11.0 min for M21, 12.9 min for M17 and 16.3 min for M1) and economical method suitable for measuring the concentration of the major metabolite, M17, and for routine monitoring of CyA-treated patients.

Reduction of colonization and infection rate during pediatric intensive care by selective decontamination of the digestive tract.

OBJECTIVE: To compare the effects of two different antibiotic regimes on the colonization and infection rates of critically ill pediatric patients. DESIGN: A prospective randomized trial. SETTING: A pediatric ICU in a university hospital. PATIENTS: Fifty critically ill pediatric patients who required intensive care for at least 4 days were randomly allocated to either the selective parenteral and enteral antisepsis regimen (treatment group, n = 25) or the control group (n = 25). INTERVENTIONS: The treatment group received oral nonabsorbable antimicrobial agents (polymyxin E, gentamicin, and amphotericin B) and parenteral cefotaxime, whereas the control group received either perioperative antibiotic prophylaxis or antibiotic therapy according to clinical or microbiological evidence of infection. RESULTS: Both groups were comparable for age, body weight, sex, and severity of illness. Colonization with Gram-negative microorganisms and yeasts in the oropharynx, and digestive and respiratory tracts increased rapidly up to 52% in the control group, whereas there was no colonization with these microorganisms in the treatment group. The occurrence rates of acquired secondary infections in the control and treatment groups were 36% and 8%, respectively (p less than .025). There were no differences between groups in the duration of intensive care or mortality rate. CONCLUSION: Selective oropharyngeal and gastrointestinal decontamination combined with systemic cefotaxime application allows for a significant reduction of the colonization rate with Gram-negative bacteria and yeasts in critically ill pediatric patients undergoing prolonged intensive care. In addition, it significantly reduces the Gram-negative infection rate of the respiratory system. However, this therapeutic approach does not alter ICU length of stay or mortality rate.

[Determination of theophylline serum level: comparison between a rapid test (enzyme-immuno-chromatography) and conventional fluorescence polarization immunoassay]. / Theophyllin-Serumspiegelbestimmung: Vergleich zwischen Schnelltest (Enzym-Immuno-Chromatographie) und konventionellem Fluoreszenz-Polarisations-Immunoassay.

To evaluate the reliability and accuracy of a rapidly performed enzyme immunochromatography method for measuring the serum concentration of theophylline, we compared it with a conventional technique (fluorescence-polarisation immunoassay). We investigated 103 venous blood samples from children and adolescents with bronchial asthma, medicated with sustained-release theophylline preparations. There was a highly significant correlation of the measured values; with a few exceptions, the individual values scattered only narrowly around the regression line. Based on this close correlation, the investigated enzyme immunochromatography test can be recommended for rapid theophylline serum level determinations in clinical practice.

Pharmacokinetic data of propranolol enantiomers in a comparative human study with (S)- and (R,S)-propranolol.

The pharmacokinetics of (S)-propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)-propranolol. The results of this study indicate that the bioavailability of (S)-propranolol, as expressed by the mean area under the concentration-time curve (AUC) and maximum serum concentration, is lower after 40 mg of the optically pure drug than after the racemic drug.

[Cyclosporin A as a diabetogenic cofactor]. / Cyclosporin A als diabetogener Kofaktor.

Two kidney transplanted patients are reported, who developed an insulin dependent diabetes mellitus after crossing therapeutic Cyclosporine A levels. After stabilisation of the Cyclosporine A levels the insulin dependent diabetes mellitus was completely reversible. The results are indicating Cyclosporine A as the insulin dependent diabetes mellitus initiator.

Effects of anticonvulsive drugs on the activity of gammaglutamyltransferase and aminotransferases in serum.

A cross-sectional study was performed to define patients at risk of developing liver disease due to long-term treatment with anticonvulsive drugs. The activities of gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase and the concentrations of primidone, phenobarbital, phenytoin, and valproic acid in serum were estimated. Epileptic children before therapy were used as controls. The results indicated enzyme induction due to phenobarbital and both enzyme induction and liver cell damage or plasma membrane leakage due to phenytoin. Gamma-glutamyltransferase may be an early indicator of liver disease due to valproic acid.

[Centrifugal blood pump (animal experiments) (author's transl)]. / Die Zentrifugalblutpumpe im Experiment.

A new centrifugal blood pump (Medtronic 1861), suitable as an extracorporeal left ventricular assisting device was tested in vitro with respect to its efficiency and haemolysis. Cannulation was carried out by applying the Zwart technique. Additionally, comparative investigations into haemolysis were performed by using the centrifugal pump and an occlusive roller pump at equal output levels. Moreover, the haemodynamic efficiency of the centrifugal pump in combination with the Zwart cannulation technique was tested in landrace pigs. When the described centrifugal pump and tube system were used, a sufficient pump output and a low rate of early haemolysis could be observed. By applying the centrifugal pump together with the Zwart cannulation technique and conical tubes specially shaped, a complete relief of the left ventricle could be attained experimentally.

Tumor host relations. V. Nitrogen metabolism in Yoshida sarcoma-bearing rats. Reduction of growth rate and increase of survival time by administration of physiological doses of branched-chain amino acids.

The continuous administration of physiological doses of the branched-chain amino acids leucine, isoleucine, and valine (Leu-Ile-Val) to Yoshida sarcoma-bearing rats caused a significant increase in the survival time by 32% and a significant reduction of tumor size after 3 weeks of growth by 33%. The shift of the nitrogen balance to negative values during the cachectic stage was delayed but not prevented. On the average, less nitrogen (-47 mg/day) were lost by Leu-Ile-Val treated rats compared with untreated tumor-bearing animals (-91 mg N/day). It appeared that Leu-Ile-Val increased the synthesis of carcass proteins, while it left the proteolysis rate unchanged, since the excretion of urea and creatinine was unaffected by these amino acids. The daily excretion of alpha-ketoglutarate, which is correlated with tumor size during the early stage of growth, was decreased during the first 2 weeks by Leu-Ile-Val, but remained for a longer period on a high level than in untreated tumor bearers. The results point to an improvement of the metabolic resistance against carcass protein depletion of the tumor-bearing host by the administration of branched-chain amino acids.

Tumor host relations. VI. Is alpha-ketoglutarate a tumor marker? Association with tumor extent in humans--correlation with tumor size in rats.

A 4-year survey is presented on the alpha-ketoglutarate (KG) values in whole blood of 200 patients with malignant neoplasms mainly of the gastrointestinal tract and the female breast. A group of patients with benign surgical diseases served as control. KG showed an association with the extent of the primary tumor classified according to the TNM-scheme. The percentages of single values above the 2s-range of the control were as follows: T2: 18%,T3: 41%, and T4: 64%. The mean value of KG had highly significantly increased already in stage T2 as compared to the control group. Rats bearing the Yoshida sarcoma showed a significant correlation between the tumor size and the daily excretion of KG into urine during the early stage of tumor growth. The results suggested that KG cannot be regarded as an early tumor marker in humans, but may be of some value as an aid for the differential diagnosis in advanced tumor stages.

Tumor host relations. II. Influence of tumor extent and tumor site on plasma cortisol of patients with malignant diseases.

The increase of plasma cortisol in patients with tumors of five different sites compared with a control group of patients with benign surgical diseases amounted to: +39% (breast), +34% (stomach), +86% (intestine), +60% (skin) and +194% (gall bladder). The first detectable increase of cortisol occurred in patients with tumors classified T 2 according to the TNM scheme (+27% above the control). Highly significant increases were observed for T 3 (+82%) and T 4 (+77%) patients. Patients with palpable lymph nodes showed a most significantly increased cortisol mean value compared with patients without palpable lymph nodes. Similarly, the cortisol mean value of patients with distant metastases was significantly higher than the corresponding value of tumor patients without distant metastases. The question remains open, whether the primary site, the extent of the tumor or the occurrence of metastases is the main determinant for the cortisol increase.