Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

BACKGROUND: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. OBJECTIVE: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. RESULTS: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Adenovirus infection among pediatric patients with cancer and in pediatric recipients of hematopoietic stem cell: A multicenter nationwide study.

The aim was to evaluate the incidence, clinical course, and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of hematopoietic stem cell. Over a 72-month period, all-in 5599 children with cancer: 2441 patients with hematological malignancy (HM) and 3158 with solid tumors (ST), and 971 patients after transplantation: 741 after allogeneic (allo-HSCT) and 230 after autologous (auto-HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; P < .001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (P < .001), including 78 (10.5%) patients after allo-HSCT and 3 (1.3%) after auto-HSCT. Time to develop AdVI was short, especially after allo-HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first-line therapy was cidofovir. None of the cancer patients died due to AdVI, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients, AdVIs are rare and associated with very good prognosis even without specific treatment. However, in allo-HSCT recipients, disseminated disease with fatal outcome is more likely to occur.

Multidrug-resistant bacterial infections in children undergoing haematopoietic stem cell transplantation over a 6-year period: analysis of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

AIMS: Multidrug-resistant (MDR) bacteria are an emerging cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). The aim of the study was to analyse the incidence, clinical characteristics and survival from bacterial infections (BI) caused by MDR pathogens in paediatric HSCT recipients. METHODS AND RESULTS: Among 971 transplanted patients, BI were found in 416 children between the years 2012 and 2017. Overall, there were 883 bacterial episodes, which includes 85·8% after allo-HSCT and 14·2% after auto-HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections. CONCLUSIONS: Regarding HSCT type, we did not find differences in the profile of MDR BI between allo- and auto-HSCT recipients. However, survival in MDR and non-MDR infections was comparable. SIGNIFICANCE AND IMPACT OF THE STUDY: The large sample size enables unique analysis and makes our data more applicable to other paediatric HSCT centres. In the absence of local epidemiological data, presented clinical characteristics of MDR-caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR aetiology and thus promptly initiate adequate antibiotic therapy and further improve patients' outcome.

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

Incidence of Infectious Complications in Children With Acute Lymphoblastic Leukemia Treated With Hematopoietic Stem Cell Transplantation.

OBJECTIVE: We analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, over a 2-year period. PATIENTS AND METHODS: Hospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI). The majority of patients (40/67; 59.7%) underwent HSCT from matched unrelated donors (MUD). RESULTS: In total, 84 BI in 31 patients, 93 VI in 50 patients, and 27 FI in 22 patients were diagnosed. No differences were found in the frequency of occurrence of BI according to the type of transplant (P = .16); the occurrence of VI was statistically more frequent in MUD transplant recipients as compared with matched sibling donors (MSD) and mismatched related donors (MMFD; P = .001) and there was a trend in MUD patients for the higher occurrence of FI in comparison with MSD and MMFD transplants (P = .08). Regarding disease status, the occurrence of BI, VI, and FI was statistically more frequent in children who underwent transplantation in their first complete remission (CR1), rather than those who underwent transplantation in ≥CR2 (P < .05). In conclusion, infectious complications are an important cause of morbidity in children with ALL treated with allogeneic HSCT and the incidence of infections is high in this group of patients.

Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

BACKGROUND: Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE: The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS: In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS: In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS: The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant.

Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study.

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.

DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.

BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.

Death-associated protein kinase 1 variation and Parkinson's disease.

BACKGROUND AND PURPOSE: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson's disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease. METHODS: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson's disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson's disease, 344 controls) and five separate Caucasian series' (combined sample size 1962 Parkinson's disease patients, 1900 controls). RESULTS: We observed no evidence of association for rs4877365 and rs4878104 and risk of Parkinson's disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. CONCLUSION: These specific DAPK1 intronic variants do not increase the risk of Parkinson's disease. However, further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins.

Calbindin-1 association and Parkinson's disease.

BACKGROUND AND PURPOSE: Calcium levels have been proposed to play an important role in the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient-control series. METHODS: We genotyped rs1805874 in four independent Caucasian patient-control series (1543 PD patients, 1771 controls). RESULTS: There was no evidence of an association between rs1805874 and disease risk in individual populations or in the combined series (odds ratio: 1.04, 95% CI: 0.82-1.31, P = 0.74). DISCUSSION: Our study shows there is no association between rs1805874 and risk for PD in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity.

GRN 3'UTR+78 C>T is not associated with risk for Parkinson's disease.

BACKGROUND AND PURPOSE: A single nucleotide polymorphism in the 3'-untranslated region of the progranulin gene (GRN; 3'UTR+78C>T; rs5848) was reported to alter the risk for frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). rs5848 is located within a micro-RNA binding site and affects the expression of GRN. METHODS: As FTLD-U patients often present with parkinsonism, we investigated the association of GRN rs5848 and risk of Parkinson's disease in two Caucasian patient-control series (n = 1413) from the US and Poland. RESULTS: No association was observed between rs5848 and susceptibility to Parkinson's disease (individual series and combined analysis). CONCLUSIONS: This finding shows that GRN rs5848 does not affect the risk of Parkinson's disease in the US and Polish populations.

Imatinib is a substrate for various multidrug resistance proteins.

UNLABELLED: An increasing resistance to imatinib is an emerging problem in patients with chronic myeloid leukemia (CML). The aim of the study was to asses mechanisms related to cellular drug resistance in imatinib-resistant derivates of chronic myeloid leukemia K-562 cell line. A parental K-562 and its imatinib-resistant derivate cell lines were used. Cell lines were tested for cytotoxicity of imatinib, cytarabine, busulfan and etoposide by the MTT assay. The cytotoxicity was expressed as IC50, inhibitory concentration for 50% of cells. Multidrug resistance proteins expression, rhodamine retention and daunorubicin accumulation were measured for each cell line. Continuous exposition of K-562 cell line to 0.01-0.02 mM imatinib resulted in development of resistance, while exposition to 0.1 microM imatinib increased cell sensitivity to this drug. There was a high correlation between PGP, MRP1 and LRP expression and IC50 values for imatinib and etoposide. All tested cell lines were highly resistant to cytarabine. Rhodamine retention alone and in the presence of cyclosporine was the lowest in imatinib-resistant K-562R-0.1 cell line, what suggest high PGP activity in this cell line. The highest daunorubicin accumulation was observed in parental K-562 cell line, while it was lower in imatinib-resistant cell lines. These data suggest that imatinib is a substrate for multidrug resistance proteins, and an increased expression of PGP, MRP1 and LRP play a role in resistance to imatinib in CML. KEYWORDS: imatinib, multidrug resistance proteins, chronic myeloid leukemia, PGP, MRP1, LRP.

Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in patients with Parkinson's disease.

Elevated levels of homocysteine have been observed in Parkinson's disease (PD) patients treated with levodopa. However, it is not studied if duration of PD or PD per se is associated with hyperhomocysteinemia. In the present study, the levels of homocysteine in 99 levodopa-treated PD patients, 15 untreated PD patients and 100 controls were examined. We focused on the influence of levodopa dose, duration of therapy and disease as well as genetic (C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism) and environmental factors. We found that levodopa-treated PD patients had elevated homocysteine plasma levels as compared to controls (p < 0.05), but the levels did not depend on levodopa doses. Another factor influencing homocysteine level was the duration of PD (p < 0.001). The frequency of allele C677T of MTHFR gene did not differ between PD and controls. In conclusion, hyperhomocysteinemia is associated with the duration of PD and levodopa treatment and possibly also with PD per se.

In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype.

The aim of this study was to define the co-occurrence of behavioural symptoms and Alzheimer's disease (AD) in relation to apolipoprotein E (APOE) genotype. Probable AD patients from the Alzheimer's Day Clinic (n = 139) were assessed with the 'Behavioural Pathology in Alzheimer's Disease' rating scale, and their APOE genotype was determined. This study demonstrated no relationship between presence of the APOE epsilon4 allele and any of the behavioural symptoms assessed, including delusions, hallucinations, depression, activity disturbances, aggressiveness and anxiety. Activity disturbances, delusions, hallucinations and aggressiveness paralleled the severity of AD, increasing in frequency with the severity of the dementia. The prevalence of delusions, hallucinations, aggressiveness and depression were found to be associated with lower levels of education.

[Vascular risk factors in demented elderly: analysis of Alzheimer Clinic materials]. / Naczyniowe czynniki ryzyka wybranych zespolów otepiennych--analiza materialu Poradni Alzheimerowskiej.

UNLABELLED: In recent years evidence is increasing that vascular disease is associated with cognitive impairment and dementia. Moreover, presence of cerebrovascular disease may intensify the clinical symptoms of Alzheimer's disease (AD). The aim of the study was to determine the prevalence of vascular risk factors in age and sex matched patients with dementia. We studied 109 patients with AD and 37 patients vascular dementia (VD). DSM-III-R test for dementia, NINCDS-ADRDA guidelines for AD and NINDS-ARIEN for VD were applied. RESULTS: Mean age of dementia onset in AD and VD was 65.8 SD 7.8 and 67.4 SD 7.0 years (p > 0.05), the duration of dementia, MMS and GDS for patients with AD and VD was not significantly different. Arterial hypertension was associated in 51.3% VD and 30.3% AD (p < 0.05), hypotension in 11.1 and 23.6% respectively (p > 0.05), atrial fibrillation was similar in AD and VD, coronary artery disease was presents 64.8% AD and 46.8 VD (p > 0.05) and type 2 diabetes in 21.6% and 10.1% (p > 0.05) respectively. No significant differences in serum lipid profile were found in both groups, except two times higher incidence of normal HDL-cholesterol concentration in AD compare to VD. The relation between alcohol consumption, cigarette smoking and head trauma was similar in both types of dementia. CONCLUSION: Vascular disease and AD have to some extent a shared aetiology, and risk factors that they have in common increase the risk of both disorders independently and vascular disease is perhaps involved in the aetiology of AD.

[Frequency and intensity of behavioral and psychological symptoms in the course of Alzheimer's disease]. / Czestosc oraz intensywnosc wystepowania zaburzen psychicznych i zachowania w otepieniu o róznym nasileniu w przebiegu choroby Alzheimera.

The aim of the study was: 1) to estimate the occurrence and intensity of some psychopathological symptoms in the course of Alzheimer's disease, and 2) to examine whether the occurrence of behavioral and psychological symptoms increases with the deepening of dementia process among persons with Alzheimer's disease living in their homes with outpatient treatment. The study was conducted among 94 persons (38 men and 56 women ageing from 52 to 86 years (x = 72.4 +/- 6.9), with education: from 2 to 17 years (x = 11.2 +/- 3.7). Three subgroups were selected for study with regard to the intensity of dementia process, estimated according to Clinical Dementia Rating (CDR): very mild (n = 16, x = 71.4 +/- 6.7), mild (n = 43, x = 72.6 +/- 7.9), moderate (n = 35, x = 72.5 +/- 6.9). Subjects in group II and III fulfill diagnostic criteria of dementia according to ICD-10, DSM IV and criteria of probable AD according to NINCDS-ADRDA. In the estimation of occurrence of behavioral and psychological disturbances: Alzheimer's Disease Assessment Scale--non-cognitive behavior (ADAS-non-cog) and subscale "Change in Personality, Interests, Drive" of Blessed Dementia Scale were used. The results have shown that with the progress of dementia process, the occurrence of the following psychopathological symptoms such as: hallucinations, intensive motor activity, purposeless hyperactivity, pacing, rigidity increases and there is a relinquishment of hobbies. In addition, regardless of the stage of dementia, such behaviors as: apathy, depression, tearfullness, impaired emotional control and disturbances of appetite were observed relatively frequently.

Lipid metabolism parameters in patients with Alzheimer's disease and their first degree relatives.

Recently, it was suggested that the presence of total cholesterol (TC), age and sex interaction in Alzheimer's type dementia (AD) is linked with the apolipoprotein E (APOE) genotype. Our objective was to determine whether the serum lipid profile in AD patients and their first degree non-demented relatives of a certain age (NDR) was dependent on APOE genotype. We included 28 mild to moderate AD and 30 NDR according to DSM-III-R and NINCDS-ADRDA criteria. NDR individuals were investigated in an age group similar to the AD group (brother-sister relationship) and in a group including younger individuals (AD patients-children relationship). Our data indicate significant differences between decreased total cholesterol and low density lipoprotein cholesterol ratio in the group of AD patients versus NDR individuals of similar age, independent of APOE genotype, and an increased total cholesterol and low density lipoprotein cholesterol ratio in a group of AD patients versus their children of the same genotype. There was no significant correlation between triglycerides and high density lipoprotein levels with APOE genotype in any of the tested groups. In conclusion, there was a decreased selected lipid serum profile parameters in AD compared to age matched non demented first degree relatives.

[Patterns of cognitive impairment and apolipoprotein genotype in persons with Alzheimer's disease]. / Wzorce aktywnosci poznawczej a polimorfizm apolipoproteiny E w chorobie Alzheimera.

The aim of this study was to test the possible relationship between patterns of cognitive deficits--especially impairment of memory processes--and ApoE genotype in patients with AD. Fifty seven right-handed subjects (31 males and 26 females) were tested in this study. The age of subjects ranged from 50 to 79, the education lasted from 11 to 16 years. All subjects were diagnosed as probable AD patients on the basis of DSM IV and NINCDS-ADRDA criteria. Each subject was examined for: 1) ApoE genotype, 2) general level of activity (GDS and MMSE), 3) neuropsychological evaluation of cognitive processes, using full test battery. 37 patients had at least one of ApoE epsilon 4 allele (e2/4, 3 and 4/4) and 20 patients had none of ApoE 4 allele (e 2/3 and 3/3). The group of tested subjects were subdivided into 2 groups. The first group was comprised by 31 patients with 3-rd stage (according to GDS) of mental activity. Twenty six patients with 4-th stage were included into the second group. Those subgroups did not significantly differ if age, education, gender or ApoE allele were considered. Experimental data were normalized and then analyzed using a statistical package SPSS/PC+. The analysis of variance showed that the type of test, stage of disease and two-way interaction ApoE x type of test were highly significant (P < 0.0001). Some results were obvious and not surprising (e.g. that results of patients with 4-th stage were much worse than the results of patients with stage 3-rd). It turned out that the best results were obtained by our patients in naming tests, the worst--in learning test with distraction. Patients with ApoE epsilon 4 performed better than patients with none ApoE epsilon 4 in the Rey's test, in the similarity test and in the test which required repeating numbers starting from the last one. The differences between the subgroups of patients with different ApoE alleles were confirmed by different distributions of correlations. All statistical analyses were repeated for more homogenous group of patients (only with stage 3-rd). The pattern of results resembled the previous one (i.e. better performance in the same tests) with one exception: additionally, in delayed recall test patients with none ApoE epsilon 4 performed much better that ApoE epsilon 4. Our results showed that some cognitive processes depended on ApoE genotype. Patients with none ApoE epsilon 4 genotype had less severe deficits in delayed recall of new information. On the other hand, working memory appeared to be less affected in patients with ApoE epsilon 4 genotype. Independent of genotype, both group showed similar impairment of learning ability without deficits in remote memory.

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland.

The p53 mutation spectrum can generate hypotheses linking carcinogen exposure to human cancer. Although it is well-documented that tobacco smoking is a major cause of lung cancer, the contribution of air pollution is less well-established. We determined the molecular and immunohistochemical changes (p53 gene mutations, p53 protein accumulation and WAF1 protein expression) and genetic polymorphisms of GSTM1, CYP1A1 and CYP2D6 genes in a case series of non-small-cell lung cancers from Silesia. This region of southern Poland is highly industrialized with considerable environmental pollution. More than 50% of lung cancers (90/164) contained p53 mutations and 75% showed the combined alteration of the p53 gene and protein accumulation. Males occupationally exposed to coal-derived substances showed a relatively high frequency of squamous and large-cell carcinomas, relatively frequent mutations in codon 298 of p53 and a low frequency of p53 immunohistochemically positive tumours. Codon 298 GAG-->TAG mutations have rarely been found in lung cancers in other populations. We found no correlation between WAF1 protein expression and mutations in the p53 gene or p53 protein accumulation. No statistically significant relationship was found between p53 mutations and GSTM1, CYP1A1, CYP2D6 genotypes. Never smokers with lung cancers from Silesia had a higher frequency of G:C-->T:A transversions than previously reported of the p53 mutation spectrum in never smokers (6/15 vs 4/34; P = 0.06 by chi2). These data are a tentative indication that occupational and environmental exposure to polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, in polluted air contributes to the molecular pathogenesis of lung cancer in never smokers.