Serum lipids and neopterin in urine as new biomarkers of malnutrition and inflammation in the elderly

ObjectiveLevels of serum lipids are influenced by malnutrition and inflammation. The study aimed to find the relation of the lipidogram to positive and negative markers of inflammation in geriatric patients. Attention was paid to neopterin in urine as a non-protein positive bioindicator of inflammation.MethodsIt was a local, monocentric, prospective clinical study in hospitalized patients older than 80 y. The study included 101 patients (54 women, 47 men). The average age of the entire group was 85.37 ± 4.88 y. The dependence of the values of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triacylglycerols (TAGs) on C-reactive protein (CRP), neopterin in urine, and prealbumin was examined.ResultsWhen we compared CRP and serum lipids, we found a statistically significant negative correlation between levels of CRP and total cholesterol (P < 0.05), HDL (P < 0.01), and LDL (P < 0.05). Also the level of neopterin in urine was negatively correlated with levels of total cholesterol (P < 0.05) and HDL (P < 0.01). A statistically highly significant interaction was demonstrated between levels of prealbumin and total cholesterol (P < 0.001), HDL (P < 0.001), LDL (P < 0.001), and TAG (P < 0.05).ConclusionA significant negative correlation between levels of inflammation markers (neopterin in urine, CRP) and total cholesterol and HDL was found. LDL was influenced to a lesser extent. A close relation between serum lipids and prealbumin was also demonstrated. Total cholesterol, HDL, and LDL can be considered novel biomarkers of malnutrition and inflammation in geriatric patients.     

Prognostic factors and risk assessment in chronic myelomonocytic leukemia: validation study of the M.D. Anderson Prognostic Scoring System

Chronic myelomonocytic leukemia continues to be a poorly understood disease, defined by clinical rather than biological features, with no consensus on optimal therapy. In the past, patients were often assessed for risk using scoring systems developed for other diseases, notably the International Prognostic Scoring System commonly used for myelodysplastic syndrome. The M.D. Anderson Prognostic Scoring System, using hemoglobin, absolute lymphocyte count, peripheral blood immature cells, and bone marrow blasts, was developed specifically for CMML; it was based on retrospective analysis of 213 patients. This report re-examines the validity of this scoring system based on follow-up of the initial cohort and prospectively examines its validity in 250 new patients. Both the original MDAPS system and a modified version derived from data of the initial cohort after extended follow-up (substituting lactate dehydrogenase for bone marrow blasts) effectively stratify both patient cohorts by survival and provide a useful risk assessment tool and additional guidance during treatment decisions.     

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in risperidone patients versus antipsychotic-naive subjects may relate to risperidone's different pharmacodynamic mechanism.     

Effects of chlorpromazine and lorazepam on explicit memory,repetition priming and cognitive skill learning in healthy volunteers

To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word-completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems.     

The effect of polymolecularity on the radius of gyration of stiff polymer chains

The z-average of the unperturbed mean-square radius of gyration, 〈S² 〉_o,z, is calculated for polymolecular Kratky-Porod worm-like chains, commonly used to represent stiff polymer chains. Polymolecularity correction factors for the Schulz-Zimm and logarithmic normal distribution functions are tabulated. By contrast with those for unperturbed random coils, they depend significantly on the chain length.     

Response to Treatment in Acute Non-lymphatic Leukaemia: Prognostic Value of Colony Forming and Colony Stimulating Capacities of Bone Marrow and Blood Cells Compared to Other Parameters

Growth of bone marrow and mononuclear white blood cells (MWBC) in soft-agar cultures was studied in 26 patients with untreated acute non-lymphocytic leukaemia (ANLL). Marrow and MWBC from 30 healthy volunteers served as controls. All ANLL patients revealed an abnormal growth in vitro . Patients with an increased number of clones in marrow cultures and large cluster predominance ('excessive growth') responded poorly to therapy with only one of 10 patients entering remission. On the contrary, only two of the 15 patients with a decreased clone number ('low growth') failed to achieve remission. The number of colonies and clusters in both bone marrow and blood cultures was significantly lower at presentation in patients who later entered remission than in those who did not. The correlations between the number of colonies and clusters in the blood and the marrow cultures were statistically significant. No significant correlations were found between prognosis or colony formation, on one hand, and the production of colony stimulating activity (CSA), by bone marrow and blood cells of ANLL patients, on the other. Nor could such correlations be found between prognosis, blood cell counts, and age. It is concluded that the growth pattern of both bone marrow and circulating colony forming cells is of value in predicting the response to cytostatic drugs and particularly in selecting patients with a high probability to respond poorly to current cytostatic regimes.     

Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome

We have previously reported that high levels of cellular vascular endothelial growth factor (VEGF) protein correlated with short survival of patients with acute myeloid leukaemia (AML). As VEGF exerts its effects via two receptors, VEGF receptor 1 (VEGFR-1) and VEGFR-2, we evaluated the significance of VEGFR-1 and VEGFR-2 protein levels in AML and myelodysplastic syndrome (MDS), and their relationship to VEGF protein levels. Western blot analysis and radioimmunoassay confirmed and quantified specific protein levels in bone marrow samples from 41 MDS and 66 AML previously untreated patients. VEGFR-1 levels were significantly higher in AML than in MDS (P = 0.0004), but no significant difference was found in the VEGFR-2 levels (P = 0.5). No significant correlation between VEGFRs levels and duration of survival was found. VEGF protein levels were significantly higher in MDS than in AML (P < 0.0001). A Cox proportional-hazard regression model showed increasing VEGF levels to significantly correlate with shorter survival of patients with MDS (P = 0.008), a finding similar to our previous report of the inverse relationship between VEGF levels and survival of AML patients. We found a significant correlation between VEGF and VEGFR-2 levels in both AML and MDS (P < 0.0000001 andP < 0.0002 respectively) but not between VEGF and VEGFR-1 levels. These data suggest that VEGF expression, rather than the expression of its receptors, is the determining factor in the biological behaviour of AML and MDS, and that VEGFRs are differentially expressed in AML and MDS.     

Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies

We explored the safety and efficacy of rituximab plus alemtuzumab in patients with relapsed or refractory lymphoid malignancies. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.