Zdenek Zadak

Intestinal permeability in patients with chemotherapy-induced stomatitis.

Purpose: Mucositis represents one of the most common side effects of chemotherapy, and may affect any part of the gastrointestinal tract, resulting in stomatitis, dysphagia, dyspepsia, or diarrhea. The aim of the present study was to evaluate intestinal permeability in patients with stomatitis during treatment with oral granulocyte-monocyte colony-stimulating factor (GM-CSF, Leucomax). Methods: Ten patients with chemotherapy-induced stomatitis and 21 control cancer patients were included in the study. Intestinal permeability in patients with stomatitis was evaluated before and after the treatment with oral GM-CSF (200 μg for 4 consecutive days) by measuring urinary lactulose, D-xylose, and mannitol after oral challenge in collected urine using capillary gas chromatography. Results: Mean grade of stomatitis (3, range 2–3) improved during treatment by a mean of 1 grade (range 0–2, sign test P < 0.05) with an improvement observed in eight of ten patients. Lactulose excretion, lactulose/mannitol, and lactulose/xylose ratios were markedly elevated in the patients with mucositis compared with 21 control cancer patients (1.60 ± 1.04%, 0.2446 ± 0.2937, and 0.3877 ± 0.6808 vs 0.35 ± 0.20%, 0.0332 ± 0.0148, and 0.0255 ± 0.0086, respectively, Mann Whitney U-test, P < 0.001). After treatment, lactulose excretion, lactulose/mannitol, and lactulose/xylose ratio decreased significantly (1.60 ± 1.04 vs 0.63 ± 0.42%; 0.2446 ± 0.2937 vs 0.1303 ± 0.1149; and 0.3877 ± 0.6808 vs 0.1126 ± 0.1146, respectively, P < 0.05). Conclusions: Lactulose excretion after oral challenge, lactulose/mannitol, or lactulose/xylose ratio may be useful markers for intestinal involvement in chemotherapy-induced mucositis. Improvement of oral mucositis was associated with a significant decrease of intestinal permeability to lactulose. Testing of intestinal permeability by the present method may be useful to evaluate the effect of therapeutic interventions in patients with chemotherapy-induced mucositis.

Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents.

The diagnosis and assessment of the severity of intestinal mucosal damage in cancer patients treated with cytotoxic drugs still rely on anamnestic data. There is cumulative evidence that measurement of intestinal permeability may represent a sensitive indicator of intestinal damage by cytotoxic agents. The intestinal permeability testing is based on differential permeability of tight junctions along the crypt-villus axis to nonmetabolized sugars. Cytotoxic drugs induce flattening of villi, leading to increased exposure of luminal contents to crypts and increased disaccharide absorption. An increased disaccharide/monosaccharide ratio and decreased xylose absorption have been described in patients treated with different cytotoxic drugs across a spectrum of malignant tumors that correlated with clinical manifestations, and were used to monitor the effect of therapeutic interventions.

Interleukin-1α Injection Into Ventromedial Hypothalamic Nucleus of Normal Rats Depresses Food Intake and Increases Release of Dopamine and Serotonin

A microdialysis injector probe administered IL-1alpha into ventromedial hypothalamus (VMN) and concurrently measured release of dopamine (DA), DOPAC, 5-HT, and 5-HIAA. After baseline dialyses, six rats received 2-ng IL-1alpha and six rats received vehicle (1 microl saline) into VMN. Sixty minutes later, food was provided for 40 min while VMN monoamines were measured every 20 min. Vehicle had no significant effect on monoamines, their metabolites, or food intake. Food intake was significantly lower in IL-1alpha rats vs. controls (p < 0.01). Baseline levels of VMN monoamines (pg/10 microl dialysate) in IL-1alpha and vehicle groups were similar. DA and 5-HT rose immediately on injecting IL-1alpha and remained higher (p < 0.05) than basal during the first 60 min and 40 min sampling period, respectively. Levels of 5-HIAA also increased (p < 0.01). Eating decreased VMN DA in controls, and decreased VMN DOPAC in IL-1alpha-treated rats. During eating, VMN 5-HT in control rats significantly increased while increasing VMN 5-HIAA occurred in IL-1alpha rats. Findings show that an IL-1alpha pathophysiological dose injected into the VMN was associated with anorexia and significantly increased dopaminergic and serotonergic activities and suggest that enhanced VMN DA and 5-HT activities may be part of an IL-1alpha-initiated cascade involved in IL-1alpha-associated anorexia.

Biochemical profile and survival in nonagenarians

OBJECTIVES Old age is associated with an increase in frequency of disorders involving virtually all organ systems, resulting in a rise of mortality. The aim of the project was to study the relationship between biochemical markers and all-cause mortality in a defined age group. DESIGN AND METHODS Thirty-eight nonagenarians, aged 92 +/- 2 (range 90-100) years entered the study. At the start of the study, a sample of peripheral blood and urine were obtained for analysis of 50 basic biochemical, hematologic and biologic parameters. The assessment was then repeated in 6 to 12 months intervals. The significance of difference between surviving subjects and those who died was examined by Mann-Whitney U test and the correlation between the variables was studied by Spearman rank correlation coefficient. RESULTS During the observation period, 21 of the studied subjects died leaving 17 persons still alive at the end of the study. The mean time from the first measurement to the death was 12 +/- 10 (range 0-33) months. The mean follow-up time in surviving subjects was 31 +/- 12 (range 4-45) months. Serum vitamin E and calcium were significantly higher, and serum alanine aminotransferase (ALT) and urinary neopterin were significantly lower in survivors compared to the subjects who died. No other parameters were significantly different in survivors and in persons who died. Urinary neopterin exhibited a significant negative correlation with serum sodium concentration (RS = -0.50, p < 0.01), but the other parameters did not correlate significantly. CONCLUSION In conclusion, among the parameters studied, differences between survivors and nonsurvivors were observed only for serum vitamin E, calcium, ALT and urinary neopterin. These findings may form a basis for prospective interventional trials in this group of patients.

Severe hypocholesterolemia in surgical patients, sepsis, and critical illness

After surgery, in sepsis and various critical illnesses, factors such as severity of the acute phase response, liver dysfunction, and hemodilution from blood loss have cumulative impacts in decreasing cholesterol; therefore, degree of hypocholesterolemia often reflects severity of illness. The direct correlation between cholesterol and several plasma proteins is mediated by the parallel impact of commonly shared determinants. Cholestasis is associated with a moderation of the degree of hypocholesterolemia. In human sepsis, the poor implications of hypocholesterolemia seem to be aggravated by the simultaneous development of hypertriglyceridemia. Cholesterol and triglyceride levels reflect altered lipoprotein patterns, and the issue is too complex and too poorly understood to be reduced to simple concepts; nevertheless, these simple measurements often represent helpful adjunctive clinical tools.

Polypharmacy and malnutrition.

Purpose of reviewMalnutrition and polypharmacy increase with age and polymorbidity and their relationship is based on a number of mechanisms. The occurrence of malnutrition in both in-patients and out-patients and its dependence on polymorbidity and age are well known, but the interrelation of polypharmacy and malnutrition has been far less investigated. The countries with the highest occurrence of polypharmacy in Europe include the Czech Republic and Finland, whereas the lowest prevalence of polypharmacy is found in Norway and the Netherlands. Recent findingsThe occurrence, consequences and mutual relationship of malnutrition and polypharmacy are described. Up-to-date knowledge regarding the influence of drugs on nutritional status is summarized. SummaryThe effect of polypharmacy on nutrition is suggested from the observations that problems with nutrition occur mostly in elderly patients, and that such patients are more frequently subject to polypharmacy. It is known that about 65% of hospitalized patients have a worse nutritional status than their healthy contemporaries. A worsened nutritional status may adversely influence the process of treatment.

Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients

Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients.

Changes in cholesterol and its precursors during the first days after major trauma

SummaryBackgroundThe causes of hypocholesterolemia in the critically ill, including major trauma patients, have not yet been fully elucidated.ObjectiveWe tested the hypothesis that hypocholesterolemia is caused by decreased production of cholesterol precursors.DesignSerum concentrations of squalene, lanosterol, and lathosterol were measured on admission, and then at 24 and 48 hours after injury using gas chromatography coupled with mass spectrometry. Serum concentrations of total low-density and high-density lipoprotein cholesterol were measured on admission and every day in the first week after injury.Results83 consecutive patients with multiple trauma were examined. Significant drops in concentrations of lanosterol and lathosterol were found in the patients in comparison with the control group. The most profound drop was in lathosterol.ConclusionDecreased synthesis of cholesterol precursors is the major cause of hypocholesterolemia in patients with multiple trauma. Lathosterol concentration is proposed as a marker of cholesterol synthesis.

New equation for the prediction of resting energy expenditure during pregnancy.

OBJECTIVE The equation for the prediction of resting energy expenditure (REE) during pregnancy is unknown. The aim of this prospective longitudinal study was to determine a new equation for prediction of REE in pregnancy. METHODS A total of 152 randomly recruited healthy pregnant Czech women (nonsmokers, not users of chronic medications or abusers of alcohol or drugs, normoglycemic, euthyroid, and not anemic) were divided into two cohorts: group 1 (n=31) was used for determination of the equation for calculation of pregnant REE and group 2 (n=121) for cross-validation of this formula. The REE of the pregnant women in both study groups was examined by indirect calorimetry (REE-IC) along with anthropometry after 12h of fasting in four periods of pregnancy. A statistical comparison of three basic equations (Harris Benedict, Schofield, and Kleiber) was used for the prediction of REE. RESULTS Through correlation analysis and linear regression, a new predictive equation of REE during pregnancy (P REE) was derived from the Harris Benedict equation. We observed high concordance between values from P REE and REE-IC in group 2. Analysis of alternative predictive equations of REE with the addition of kilocalories and a corrected multiplication factor for each stage of pregnancy expressed low concordance. CONCLUSIONS The equation for REE in kilocalories during pregnancy, P REE=346.43943+13.962564 x W + 2.700416 x H - 6.826376 x A (W, weight; H, height; A, age), with SD 116 kcal/d, corresponds closely to REE-IC and maternal changes in each phase of pregnancy. P REE can be applied for prediction of REE during gestation.

Urinary Neopterin and Microalbuminuria in Patients Treated by Low-density Lipoprotein Apheresis

Abstract Low-density lipoprotein (LDL)-apheresis is a method of extracorporeal elimination of LDL-cholesterol in patients with severe primary lipoprotein disorders. LDL-cholesterol activates macrophages, which play an important role in atheromatous plaque formation. In the present study, we have investigated urinary neopterin, a specific marker of macrophage activation and microalbuminuria, an indicator of generalized vascular dysfunction, after a single LDL-apheresis procedure in 10 patients with severe primary lipoprotein disorder. The urinary neopterin/creatinine ratio was increased in patients compared to controls. No significant changes of the neopterin/creatinine and albumin/creatinine ratios were observed after LDL-apheresis, except a significant (p < 0.006) decrease of urinary neopterin/creatinine ratio in the evening after the apheresis. This decrease showed significant negative correlation with the pre-apheretic levels of atherogenic cholesterol fractions (p < 0.05) and with cholesterol decrease during the apheresis (p < 0.05). Urinary albumin/creatinine ratio correlated positively with total and LDL-cholesterol levels before the apheresis and with the evening urinary neopterin/creatinine ratio after the apheresis, but did not correlate with glycemia and triacylglycerides. Elevated urinary neopterin in the patients with severe primary lipoprotein disorders reflects the presence of atherosclerosis. A single LDL-apheresis procedure did not significantly affect microalbuminuria. The decrease of urinary neopterin in the evening after the apheresis corresponds with the diurnal rhythm of neopterin excretion and was less pronounced in patients with more severe hypercholesterolemia. The correlations between microalbuminuria, neopterin and pre-apheretic cholesterol concentrations indicate a possible connection between microvascular dysfunction, macrophage activity and severity of hyperlipidemia, but these results should be interpreted with caution because of small number of subjects evaluated.