The Relationship of Kynurenine and Neopterin Levels and Their Association with a Selection of Other Immune Markers in Chronic Myeloid Leukaemia Patients.

Among malignant diseases, chronic myeloid leukaemia (CML) is one of the best suited candidates for immunotherapy. For this purpose it is necessary to broaden the present knowledge on the immunology of this disease. As a part of such a project, the levels of kynurenine (KYN) and neopterin (NPT) were studied in 28 CML patients and in the same number of healthy subjects. At diagnosis, both KYN and NPT levels were found to be elevated in a significant portion of the patients and dependent on their leukocyte count. As in the case of KYN, increased NPT levels dropped after achieving remission. When correlating KYN and NPT levels with a selection of other markers tested, significant association was revealed only in the case of CRP and IL-6. However, there were several patients with increased KYN levels in whom NPT was not detected, and vice versa. The relapse of the disease observed in two patients was accompanied by an increased level of NPT in both cases, but by an increased level of KYN in only one of them. No significant correlation was found between KYN and NPT levels in sera taken at diagnosis. However, when the whole set of sera was taken into consideration, the association became statistically significant. Although the data obtained revealed a number of similarities between KYN and NPT production in CML patients, it also suggested a difference in the kinetics of these two biomarkers' production.

High level of Tregs is a positive prognostic marker in patients with HPV-positive oral and oropharyngeal squamous cell carcinomas.

BACKGROUND: Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. MATERIAL AND METHODS: Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. RESULTS: Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. CONCLUSION: Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence.

The Hans algorithm failed to predict outcome in patients with diffuse large B-cell lymphoma treated with rituximab.

Diffuse large B-cell lymphoma (DLBCL) consists of at least two biologically and pathogenetically different subtypes, the germinal centre B-cell (GCB) and the activated B cell type (ABC). It has been suggested that immunohistochemistry can discriminate these subtypes as well. The aim of this study was to verify the validity of the most commonly used Hans algorithm in patients with DLBCL treated with anthracycline- based chemotherapy with rituximab. Immunohistochemical staining using standard protocols was performed on formalin fixed paraffin-embedded tissues. CD20, CD5, CD23, BCL2, CD10, BCL6, MUM1 and Ki67 antibodies were applied. Out of 120 examined cases 52 patients were evaluated as GCB type and 68 patients as having non-GCB, out of a set of 99 patients treated with immunochemotherapy 45 patients with GCB and 54 patients with non-GCB DLBCL were identified. In this set of patients, there was no statistically significant difference neither in overall survival (OS) (HR 1.47 95% CI 0.51-2.63; p=0.45) nor in progression free survival (PFS) (HR 1.57, 95 % CI 0.76-3.22; p=0.731) between both groups.

[Pressure ulcer and mortality risk after surgical treatment of proximal femoral fractures in the elderly]. / Dekubitus a riziko úmrtí senioru operovaných pro zlomeninu proximálního femuru.

PURPOSE OF THE STUDY: We aimed to determine the incidence of pressure sores and their effect on survival in patients older than 70 years who underwent surgery for hip fracture, and to identify the factors which were associated with an increased risk of pressure sores. MATERIAL AND METHODS: The group comprised 269 patients (219 women and 50 men) older than 70 years who underwent surgery for proximal femoral fractures in the Trauma center between January 2003 and June 2005. Follow-up ranged from 12 to 18 months. In a prospective study we assessed relevant medical history, demographic and clinical data, pre-, intra-, and post-operative factors and the presence, location and depth of pressure sores. Statistical significance at a 5 % level of probability was determined by testing null hypotheses for qualitative and quantitative variables, using multivariate analysis adjusted for selected baseline characteristics. RESULT: The average age of the patient group was 81 years (range, 70-99). Pressure ulcers developed in 92 patients (34.2 %); their presence in the post-operative period significantly reduced patient survival (p=0.037). In terms of location, pressure ulcers in the calcaneal region had a more significant effect on patient mortality (p=0.011) than those in the sacral region (p=0.130). Age was not significantly associated with pressure ulcer development (p=0.547), in contrast to male gender (p=0.007). A lower mobility score before injury was a significant risk factor (p=0.007). Co-morbidities adjusted for age and gender had a significant effect (p=0.003). The factors that did not significantly increase the risk of pressure ulcers were as follows: the patient's living environment before injury (p=0.113), AO type of fracture (p=0.653), type of anaesthesia (p=0.702), surgical procedure used (p=0.946), morbidity before injury (p=0.267) and time to surgery (p=0.180). The presence of acute complications was of boundary significance (p=0.083). DISCUSSION The study included only the patients with proximal femoral fractures who underwent surgery. It was the authors' view that, by excluding conservatively treated patients, a more homogenous group was achieved. There is only sparse information in the literature concerning the effect of pressure ulcers on reduced patient survival, and the significance of pressure ulcer location has not been evaluated at all. Similarly, the effect of pre-morbidity on pressure ulcer development has not been reported in any of the studies available. In contrast to other studies, the authors did not find age to be a risk factor for increased ulcer development. They believe that the quality and quantity of the input data (prospective data collection, large sample size, long follow-up) guarantee the validity of the results obtained in this study. The incidence of pressure sores is in agreement with the results of relevant studies involving large numbers of patients and prolonged follow-up. CONCLUSIONS: In patients older than 70 years undergoing surgery for hip fracture, the development of pressure ulcers had a significant effect on reduced survival, with the highest significance for ulcers in the calcaneal region. Factors significantly increasing the risk of ulcer development were male gender, morbidity before injury and pre-existing chronic complications. The presence of acute complications was of boundary significance. The study did not show any significant effect of age, pre-morbidities, time to surgery, patient's living environment before injury, fracture type, type of anaesthesia or surgical procedure used on the incidence of pressure ulcers.

Long-term changes in prevalence of overweight and obesity in Czech 7-year-old children: evaluation of different cut-off criteria of childhood obesity.

The objective of this paper was an evaluation of change in prevalence of overweight and obesity in Czech children, and a comparison of cut-off points for body mass index references from the Czech Republic (CzR), International Obesity Task Force and WHO. The authors conducted a survey in 7-year-old children, and compared data from 1951, 1981, 1991, 2001 and 2008 (WHO cut-offs). 2008 data were evaluated according to different cut-offs. Results showed that since 1951 in boys, overweight prevalence increased from 13.0% in 1951 to 26.8% in 2001, in girls from 10.9% to 22.9%. Obesity increased in boys from 1.7% to 8.3%, in girls from 1.7% to 6.9%. From 2001 to 2008 obesity in boys increased; obesity in girls and overweight in both genders decreased. In 2008 cohort the following values were found: overweight and obesity: CzR criteria, percentage was lowest (14.8% boys and 11.1% girls); WHO criteria, highest prevalence (23.5% boys and 19.5% girls); obesity: lowest ratio International Obesity Task Force criteria (4.4% boys, 3.3% girls), highest ratio boys WHO criteria (10.0%), girls CzR criteria (5.0%). Overweight and obesity prevalence increased in 7-year-old Czech children since 1951; since 2001 prevalence is plateauing with exception of boys. Using different body mass index references resulted in marked differences in overweight and obesity prevalence.

[Fractures of the L5 transverse process in pelvic ring injury]. / Zlomeniny prícných výbezku L5 u poranení pánevního kruhu.

PURPOSE OF THE STUDY: The aim of the study was to record the frequency of L5 transverse process fractures associated with pelvic injuries and to find out whether in unstable pelvic fractures the frequency is significantly higher. MATERIAL AND METHODS: The group evaluated comprised 106 patients (38 women and 68 men; average age, 43.4 years; range, 16 to 95 years) treated for pelvic ring fractures at two trauma centres in the period from January 1 to December 31, 2007. Their radiographs and CT scans were retrospectively reviewed in order to identify fractures of the L5 transverse processes and to obtain exact descriptions of injuries to the dorsal pelvic structures. The results were statistically analysed using the Chi-square test with a 5 % level of significance. RESULTS: The evaluation of radiographs and CT scans identified L5 process fractures in 21 patients; none of these had type A pelvic fracture. An L5 transverse process fracture was found in 10 (15 %) of 69 patients with type B pelvic fracture and in 11 (73 %) of 15 patients with type C pelvic fracture, i.e., only in the patients with unstable injury to the pelvis classified as type C or type B. The occurrence of L 5 transverse process fractures was significantly higher in completely unstable, type C pelvic trauma than in partially unstable, type B pelvic injury (p < 0.001). DISCUSSION: Our results showed that evaluation of the radiographs was not sufficient for the identification of L5 transverse process fractures and trauma to the dorsal pelvic structures. The reason was either poor quality or incorrect positioning. This gives support to the recommendations of many authors that CT scans should be the standard method for identification of all pelvic injuries. The study also confirmed that L5 transverse process fractures are associated with unstable pelvic injuries. Their significantly high occurrence is in agreement with other relevant studies which, however, have reported the results without statistical evaluation. CONCLUSIONS: The study shows a significantly higher occurrence of L5 transverse process fractures in patients with unstable pelvic ring injuries. The finding of such a fracture should focus attention to looking for trauma to the dorsal pelvic structures.

Genetic variability of cytomegalovirus glycoprotein O in hematopoietic stem cell transplant recipients.

UNLABELLED: Genetic variation of cytomegalovirus (CMV) strains can correlate with their pathogenicity for immunocompromised patients. Glycoprotein O (gO), together with glycoprotein L and glycoprotein H, mediate the fusion of the viral envelope with the cell membrane and promotes virus penetration, envelopment, and release. The variability of gO might play a role in CMV cell tropism. The goal was a retrospective analysis of gO variability in a cohort of hematopoietic stem cell transplant (HSCT) recipients to determine the distribution of gO genotypes and to investigate their impact on clinical outcome and manifestation of CMV infection. METHODS: In archived blood samples from 51 adult allogeneic HSCT recipients with active CMV infection, gO was analyzed by sequencing the N-terminal domain of the UL74 gene using the dye deoxy termination method. RESULTS: The gO1 and gO2 clades were most common (39% and 20%, respectively, and gO3 was associated with higher risk of symptomatic infection (P = 0.026 in multivariant analysis). Despite being associated with higher antigenemia levels (P = 0.02), gO4 had the best survival and lower rate of CMV recurrence. No significant differences were found in clinical manifestation and outcome of CMV disease between patients with various gO clades. Because CMV strains sharing an identical gO sequence differed in glycoprotein B genotypes, sequencing the N-terminal part of the gO gene does not seem to be optimal for the identification of strains. CONCLUSIONS: gO genotyping may contribute to the biological characterization of CMV strains in HSCT recipients.

[Genotyping of viral glycoprotein B (gB) in hematopoietic stem cell transplant recipients with active cytomegalovirus infection: analysis of the impact of gB genotypes on the patients' outcome]. / Genotypizace virového glykoproteinu B (gB) u príjemcu transplantátu kmenových bunek krvetvorby s aktivní infekcí cytomegalovirem--sledováni vlivu genotypu na prubeh infekce.

AIM OF THE STUDY: Genetic variation of CMV strains may correlate with their pathogenicity for immunocompromised patients. On the basis of sequence variation in the UL55 gene encoding the most abundant viral envelope glycoprotein gB, CMV can be classified into four major gB genotypes. The aim of the study was the analysis of the distribution of gB genotypes in a cohort of haematopoietic stem cell transplant (HSCT) recipients and of the correlation of genetic polymorphisms with clinical outcomes and manifestation of CMV infection. MATERIAL AND METHODS: Archived DNA isolates from consecutive blood samples of 53 adult allogeneic HSCT recipients with active CMV infection, transplanted in 2004-2005, were used for the genetic analysis. HCMV gB genotyping was performed by restriction fragment length polymorphism (RFLP) analysis and sequencing of the central variable region of UL55. The association of gB genotypes with selected clinical parameters was assessed by multivariate analysis after adjustment for graft donor type, HLA-matching and anti-thymocyte immunoglobulin (ATG) therapy. RESULTS: gB1, gB2, gB3, and gB4 genotypes were detected in 30%, 17%, 26% and 4% of the patients, respectively. An atypical gB genotype was found in one patient. Co-infection with two or more gB genotypes was revealed in 17% of the patients. The distribution of gB genotypes did not vary in time, despite the fact that the patients transplanted in 2005 had more severe CMV infection with higher viral loads in the blood than those transplanted in 2004. gB1 was associated with a lower viral load (p = 0.046) and a milder course of symptomatic CMV infection, but with a higher rate of acute graft versus host disease (OR 3.4; p = 0.067). Pancytopenia was less frequent in the patients infected with gB3 (OR 0.09; p = 0.075). In contrast, gB2-infected patients had a worse outcome of CMV infection with a higher rate of organ involvement and were less responsive to antiviral therapy (OR 6.65 and 0.18; p = 0.15 and 0.12, respectively). The prognostic impact of co-infection with two or more gB genotypes was not shown. CONCLUSIONS: gB genotype may have an impact on the course of CMV infection and its complications in HSCT recipients. Nevertheless, these results need to be tested on a larger group of patients in the context of genetic variability of other functionally important viral genes. The characterization of viral genetic factors determining CMV pathogenesis will be of relevance to the treatment of patients at high risk of CMV infection.

Distinguishing of primary mediastinal B-cell lymphoma and diffuse large B-cell lymphoma using real-time quantitative polymerase chain reaction.

Primary mediastinal B-cell lymphoma (PMBL) seems to be reliably distinguished from diffuse large B-cell lymphoma (DLBCL) with microarray technology. We measured expression of Fcer2, Pdl2 and Blk genes using real-time quantitative polymerase chain reaction (RTqPCR) on formalin fixed, paraffin embedded material (FFPE) and suggested a formula to discriminate PMBL from DLBCL. For 39/82 included patients the diagnosis of PMBL was expected clinico-pathologically. Diagnosis of 10/39 and 2/43 of clinically considered PMBLs and DLBCLs, respectively, was not genetically confirmed. Compared to confirmed PMBLs, unconfirmed ones showed clinical features similar to DLBCLs, e.g. spleen infiltration (p=0,028) and decreased invasiveness in pericardium (p=0,045). They tended to have more common infradiaphragmatic involvement, less often tumor sclerosis or fluidothorax. There were no immunohistochemical differences between genetically confirmed and unconfirmed PMBLs. New approach of distinguishing PMBL and DLBCL is presented. It is based on expression of three genes in routinely available FFPE material using RTqPCR.

[Mortality risk factors in the elderly with proximal femoral fracture treated surgically]. / Rizikové faktory úmrtí senioru operovaných pro zlomeninu proximálního femuru.

PURPOSE OF THE STUDY To assess the effects of medical history, fracture type, method of treatment and complications on the risk of death in elderly patients treated for proximal femoral fracture. MATERIAL AND METHODS The group comprised of 269 patients (219 women and 50 men) older than 70 years who underwent surgery for proximal femoral fracture at the Level I Traumacentre between January 2003 and June 2005. The follow-up ranged from 12 to 38 months. In a prospective consecutive manner the following was recorded: age, gender, serious internal diseases, pre-injury level of mobility, place of living before injury, fracture type (AO classification), time between injury and surgery, anaesthesia, surgical technique, complications and death. Statistical significance at the 95% level was ascertained using null-hypothesis tests for qualitative and quantitative variables by means of multivariate analysis. RESULTS The average age of the patients was 81 years (range, 70 to 99 years). The higher the age, the shorter the time of survival (p=0.015) as each additional year reduced survival by 4.6%. The women to men ratio was 4.2:1. The male gender had a significantly shorter time of survival (p=0.007). Two and more serious internal diseases in the patient's medical history, as compared with a single one, also made survival significantly shorter (p<0.001). When, before injury, a patient moved without walking support, survival was significantly longer than in a patient using a walking cane/crutch (p=0.022) or two canes/crutches or a walker (p<0.001), or in a bedridden patient (p=0.014). The fact that, before injury, a patient was living in a pensioner's home had no effect on a shortened time of survival (p=0.136). Similarly, the fracture type (31A or 31B and subgroups) was not significant for the length of survival (p=0.903). The interval between injury and surgery was not a risk factor for survival (p=0.269). No effect of the type of anaesthesia on survival was found (p=0.450). Neither the surgical technique nor the type of implant was significant for survival time. When general internal complications occurred, they affected the length of survival significantly (p<0.001). Also, pressure sores developing in the post-operative period significantly shortened the time of survival (p=0.037). Early complications did not result in shorter survival (p=0.867), but late deep infection in ive patients significantly shortened their lives (p=0.008). Failed osteosynthesis and consequent revision surgery shortened survival time only when it occurred during the primary treatment (p=0.003); after the primary hospitalization was terminated, it had no effect on the length of survival (p=0.398). DISCUSSION The study focused attention only to elderly patients with proximal femoral fracture treated surgically. The authors suggest that, by excluding patients treated conservatively, the group became more homogeneous and a more exact assessment of each factor's effect on death risk was possible. The investigated factors were recorded only during the first year following injury; however, death was recorded by the end of the study. Using the assessment of cumulative survival, this allowed for a more accurate statistical evaluation of the effect of each factor on the risk of death. CONCLUSIONS In patients over 70 years, a significantly shorter time of survival following the surgical treatment of proximal femoral fracture was found to be related to high age, male gender, multiple morbidity in the patient's medical history, poor patient's mobility before injury, general complications, development of pressure sores post-operatively, failed osteosynthesis requiring revision surgery and deep infection of the affected hip. No relation to significantly shorter survival was found for the following factors: living in a pensioner's home before injury, fracture type, time between injury and surgery, type of anaesthesia and operative technique. Key words: hip fracture, surgical treatment, mortality, risk factors.

[Reproductive outcome after laparoscopic myomectomy--retrospective analysis 1994-2007]. / Reprodukcní výsledky po laparoskopické myomektomii--retrospektivní analýza 1994-2007.

The aim of the study was to analyse the reproductive outcome after laparoscopic myomectomy (LM) in infertile patients. Between the years 1994-2007 were 351 infertile women operated in our department. The average age of the patients was 33.5. The total number of extirpated fibroids was 643, with the average of 1.7 per patient and the average size of 3.3 cm. 171 women (48.7%) became pregnant after LM. There were 119 deliveries, 16 spontaneous abortions and 6 ectopic pregnancies in this group. The caesarean section (CS) rate was 46.2% . Intramural localisation of the fibroid significantly correlated with the termination of pregnancy by CS. I. and II. trimester pregnancy loss correlated significantly with deep coagulation when conception occurred during 12 months after surgery. No uterine rupture was observed during pregnancy.

Adiponectin as a potential marker of prostate cancer progression: studies in organ-confined and locally advanced prostate cancer.

Serum levels of adiponectin were measured in patients with benign prostatic hyperplasia and prostate cancer of pT2 and pT3 stage. Adiponectin ELISA assay, immunohistochemistry, and selected metabolic and biochemical parameters measurement was performed in 25 patients with benign prostatic hyperplasia and 43 with prostate cancer (17 patients with organ-confined and 26 patients with locally advanced disease). Serum adiponectin levels did not differ between prostate benign hyperplasia and cancer clinical stage T2, but was significantly higher in pT3 relative to pT2 group (14.51+/-4.92 vs. 21.41+/-8.12, P = 0.003). Tissue immunohistochemistry showed enhanced staining in neoplastic prostate glands and intraepithelial neoplasia relative to benign prostatic hyperplasia without distinction between disease grade and stage. Serum adiponectin levels are higher in locally advanced relative to organ-confined prostate cancer and may thus serve as an auxiliary marker providing further improvement for discrimination between pT2 and pT3 stages.

Higher content of C18:1 trans fatty acids in early human milk fat of Roma breast-feeding women.

AIM: The purpose of our study was to determine the content of trans fatty acids in early human breast milk as an indicator of dietary exposure in a sample of Roma breast-feeding women and in a sample of women from the general Czech population. METHODS: We collected samples of early human milk from 43 Prague women from the general population and 21 Roma women. After lipid extraction, the fatty acids were converted into methyl esters (FAMEs). Finally, gas chromatography with flame ionization detector (GC-FID) analysis on a CP-Sil 88 column was used to determine C18:1 trans monoenic fatty acid levels and total trans isomers fatty acid levels in human milk. RESULTS: A significantly higher content of C18:1 trans fatty acid isomers was detected in human milk fat from Roma mothers than in women of the general population (2.73 vs. 2.09%, p < 0.05). Both groups monitored did not differ in the representation of total fatty acid trans isomers. Differences in the frequency of consumption of certain TFA sources (butter, fried crisps) were established. CONCLUSIONS: The study proved a higher fatty acid trans isomers content in Roma breast-feeding mothers in the Czech Republic, and this is probably related to their bad eating habits.

[Comments to statistical methods in medical disciplines]. / Poznámky o statistice pro zdravotnické obory.

Statistical methods are nowadays one of the main tools for the evidence based medicine. This paper mentions some of the basic ideas necessary for the reader to understand usage of statistical methods.

Characteristics of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus isolated from the nasopharynx of healthy children attending day-care centres in the Czech Republic.

Nasopharyngeal carriage of potential pathogens was studied in 425 healthy 3- to 6-year-old children attending 16 day-care centres (DCCs) in nine Czech cities during the winter 2004-2005. The overall carriage of pathogens was 62.8% (Streptococcus pneumoniae, 38.1%; Haemophilus influenzae, 24.9%; Moraxella catarrhalis, 22.1%; Staphylococcus aureus, 16%). An age-related downward trend was observed for colonization with respiratory pathogens in contrast to Staph. aureus whose carriage was significantly higher among older children. The following serotypes of colonizing S. pneumoniae were the most predominant: 23F (20.6%), 6A (15.1%), 6B (12.7%), 18C (7.8%), 15B and 19F (6% each). The majority (94.3%) of H. influenzae isolates were non-typable; among capsulated isolates, serotype b was not found. Decreased susceptibility to penicillin was determined in 3% of pneumococci; 4.6% of H. influenzae strains and 85.1% of M. catarrhalis strains produced beta-lactamase. As for non-beta-lactam antibiotics, pneumococci resistant to trimethoprim-sulphamethoxazole were the most common (15.7%) among the attendees.

Iodine saturation of Roma neonates in prague is not at an optimum level.

AIM: The purpose of our study was to determine urinary iodine as an indicator of iodine supplementation in Roma (Gypsy) neonates compared to majority population neonates. METHODS: The groups studied were formed by 30 full-term Roma neonates and 151 majority population neonates. Iodine was determined from samples of urine collected on the 4th day after delivery, after alkaline ashing, using the Sandell-Kolthoff method. RESULTS: The median of urinary iodine in Roma neonates was 92.15 microg/l urine and in neonates from majority population mothers it was 109.20 microg/l urine. The mean of urinary iodine in Roma neonates was 114.55 microg/l urine (SD 71.68 microg/l) and in neonates from majority population mothers it was 141.86 microg/l urine (SD 87.42 microg/l). The difference was not statistically significant. Majority population mothers more frequently consumed nutrition supplements containing iodine as well as fish. CONCLUSIONS: Compared to older data, supplementation of neonates with iodine is higher. However, it does not reach optimum levels. The urinary iodine median in Roma neonates lies in the mild iodine deficiency band.

A study of excess mortality during influenza epidemics in the Czech Republic, 1982-2000.

Influenza related mortality rates have been established in many countries; nevertheless, studies focusing on the Central European population have been rare to date. We assess mortality attributable to influenza by comparing all cause mortality and mortality due to diseases of the circulatory system during influenza epidemic and non-epidemic periods, as defined by acute respiratory infection surveillance data. Data on total mortality, mortality due to diseases of the circulatory system and surveillance data for influenza and other respiratory infections were used in a general linear model with a logarithmic link for dependence of left censored mortality data over time, and week as a categorical factor. Results of the analysis show statistically significant (p <0.001) differences in excess mortality rates between influenza epidemic and non-epidemic periods in the Czech Republic between 1982 and 2000. We estimate that 2.17% of all cause mortality, and 2.57% of mortality due to diseases of the circulatory system throughout the study period was attributable to influenza, with an estimated annual average of 2661 and 1752 deaths respectively. The highest numbers of deaths were reported during seasons when influenza A/H3N2 was the predominant circulating strain. Improving vaccination coverage against influenza is considered to be the primary strategy for prevention of influenza associated mortality.

Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study.

We conducted a controlled, double-blind study of parenteral glutamine supplementation in an unselected group of consecutive autologous transplant patients. Patients received 30 g of alanyl-glutamine dipeptide (Dipeptiven; Fresenius-Kabi, Bad Homburg, Germany) or glutamine-free amino acid solution i.v. from day +1 to day +14 or to discharge. All patients were assessed for clinical status, mucositis, blood counts, oral intake and immune reconstitution. Parenteral nutrition was administered according to predefined guidelines. Forty patients were randomized; 21 into the glutamine and 19 into the placebo arm. Glutamine patients had less days with diarrhoea (3.3 +/- 4.0 vs 4.3 +/- 3.0, P = 0.03), but they had more severe oral mucositis (mean 4 +/- 4.7 vs 1.4 +/- 2.3 days of mucositis score >13, P = 0.04), spent more days on opioids (mean 3.5 +/- 4.2 vs 1.2 +/- 2.2 days, P = 0.03) and left hospital later than placebo patients (mean 13.5 +/- 3.1 vs 11.7 +/- 2.4 days after transplant, P = 0.06). There were more relapses (P = 0.02) and deaths (P = 0.05) in the glutamine group. The cost of supportive care (mean 2960 +/- 1694 vs 1534 +/- 513 Euro, P = 0.002) was also greater for glutamine patients, mainly due to the cost of glutamine dipeptide itself. The described mode and dosage of glutamine administration did not produce meaningful benefit in our autologous transplant patients and it was certainly not cost-effective.

Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8- tetrachlordibenzo- p-dioxin.

OBJECTIVE: More than 35 years ago, during 1965-1968, in the former Czechoslovakia, approximately 80 persons became ill due to occupational exposure to 2,3,7,8-tetrachlordibenzo- p-dioxin (2,3,7,8-TCDD). The objective of this study was to investigate the incidence of disorders related to occupational exposure to 2,3,7,8-TCDD. METHODS: Most subjects in the group of 12 former 2,3,7,8-TCDD workers (mean age 56.8 years, exposure 10 days to 23 months) still suffer from disturbances of lipid metabolism, psychic disorders, chloracne, and/or nervous system lesions. All workers were given internal, neuropsychological and ophthalmological examinations. Blood cholesterol and triglycerides were measured, and the common carotid artery was examined by ultrasound (B-mode), with the intima-media thickness (IMT) also being measured. Findings were compared with the 2,3,7,8-TCDD level in 1996. RESULTS: Nine of the 12 previously exposed workers had elevated plasma lipids, and hyperlipidaemia was statistically more frequent in patients with higher 2,3,7,8-TCDD levels ( P=0.03). Subject 1, with the highest 2,3,7,8-TCDD plasma level, had 80% stenosis of the diameter of the carotid artery, which needed acute surgery. Besides him, seven persons had atherosclerotic plaques in the carotid arteries. The mean IMT in the group was 0.85 mm (SD+/-0.19); the normal value is 0.62 mm. Eight subjects had degenerative changes of the ocular fundus. Chloracne was still present in two persons. Neuropsychological findings were assessed as normal only in three persons with lower 2,3,7,8-TCDD plasma levels in 1996. Mean 2,3,7,8-TCDD plasma level in 1996 was 256 pg g(-1) fat (range 14-760). CONCLUSION: Hyperlipidaemia, atherosclerotic plaques, increased IMT, ischaemic heart disease and neuropsychological disturbances were frequent in this group of former 2,3,7,8-TCDD workers. Hyperlipidaemia might have played an important role in most of these disorders. The level of 2,3,7,8-TCDD correlated with the highest level of triglycerides ( P=0.02) and cholesterol ( P=0.01) that was found during the 35-year follow-up. This group belongs to the most heavily 2,3,7,8-TCDD-exposed groups of workers, because the mean estimated concentration at the time of intoxication was approximately 5000 pg g(-1) plasma fat.

[Parenteral glutamine does not improve the nutritional status in patients during high-dose chemotherapy and autologous peripheral stem cell transplantation]. / Parenterální glutamin nezlepsuje nutricní stav nemocných v prubehu vysokodávkové chemoterapie s autologní transplantací periferních kmenových bunek.

BACKGROUND AND AIM: High-dose chemotherapy is aggressive treatment modality adversely affecting both energy/protein demands and oral intake/resorption of nutrients. Aminoacid glutamine is known for its' proteoanabolic effect and as an energy source for enterocytes and immune system. Nutritional parameters have been studied in a controlled, randomised, double-blinded trial of parenteral glutamine supplementation of autologous stem cell transplant patients. METHODS: Forty consecutive patients with haematological and solid cancer and multiple sclerosis were treated from 1999 to 2001 by high-dose chemotherapy with autologous stem cell transplantation. Patients were randomly assigned either for parenteral administration of 30 g of alanyl-glutamine dipeptide (Dipeptiven, Fresenius-Kabi) or isonitrogenous glutamine-free amino acid solution from day +1 to day +14 or to discharge from hospital. Patients were closely monitored from admission to day +100. Nutritional parameters included: oral dietary intake, body weight, body composition, energy expenditure, concentration of serum proteins and nitrogen balance. Parenteral nutrition in dose of 26.5 kcal/kg and 1 g of aminoacid/kg was given to patients who did not reach adequate oral intake for 5 days and withheld after three consecutive days of adequate intake. RESULTS: Nutritional assessment on admission differed according to the method used but no parameter of nutrition predicted the clinical course of treatment. Inadequate oral intake period lasted (mean +/- SD) 6.8 +/- 5.9 days, average length of stay being 17.5 +/- 3.9 days. Patients were unable to use sipping of enteral feed. Resting energy expenditure neither on admission nor in critical period differed from predicted value. Serum protein concentrations significantly decreased on discharge with normalisation as soon as to day +28, correlating inversely with changes in extracellular water content. Nitrogen urine loss was 10-16 g/day. Only 42.5% of patients were treated with parenteral nutrition. Cumulative nitrogen balance at day +9 was -30.7 +/- 24.1 g N. Body weight at day +28 significantly decreased (-2.94 +/- 4.4 kg), mostly consisting of loss of pure body cell mass. Glutamine supplementation did not improve any of the listed nutritional parameters. CONCLUSIONS: High-dose chemotherapy with autologous stem cell transplantation causes proteocatabolism of medium severity. Nutritional status of patients cannot be improved by the mode and dosage of parenteral glutamine used in our study. Optimal nutritional monitoring and treatment for this group of patients is suggested.