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Biomedical subjects

A Lange

Publications and source records attributed to A Lange.

At least 19 recordsLinked to original sources

Low CXCR4 membrane expression on CD34(+) cells characterizes cells mobilized to blood.

SUMMARY: In this work, association between the presence and membrane density of CXCR4 and the effectiveness of mobilization was studied. Ninety G-CSF mobilized PBPC and 28 native BM (nBM) preparations obtained from healthy individuals for transplantation and BM obtained after G-CSF mobilized PBPC collection in 10 donors were investigated. Positivity for CD34, HLA-DR and CXCR4 were analysed in the three colour fluorescence. The cellular profile of PBPC differed from nBM preparations with respect to lower: (i) proportion of CD34(+) cells (0.64%+/-0.04 vs 0.92+/-0.07) and CD34(+)CXCR4(+) cells (0.30%+/-0.02 vs 0.61+/-0.07); (ii) contribution of CXCR4(+) cells to CD34(+) cells (52.2%+/-2.5 vs 62.2%+/-4.2); (iii) CXCR4 epitope density in CD34(+) cells (48.9+/-5.5 vs 94.7+/-10.4). PBPC yield for CD34(+) cells was correlated with the content of CD34(+) cells lacking CXCR4 in the leukapheresis product (R=0.38). In contrast, nBM harvested for transplantation was poor in CD34(+) cells if these cells were frequently CXCR4- (R=-0.49). The present study shows that CD34(+) cells mobilized to blood were characterized with a low proportion of CXCR4 and this associated with CD34(+) cell content in PBPC.

Antigens, CD34↗

Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a lymphoproliferative disorder characterized by clonal expansion of B lymphocytes. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter/enhancer region of tumour necrosis factor-alpha (TNFA) gene and susceptibility to B-CLL. TNFA (-308 G/A) promoter single nucleotide polymorphism (SNP) was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) using commercial oligonucleotides. No significant association was found between the distribution of TNFA alleles and B-CLL in Polish patients with B-CLL. Our single centre results were compared with other literature data and combined in a cumulative analysis employing the Mantel-Haenszel method. Among 183 B-CLL patients, 47 (26%) were carrying TNFA*2 allele and this allele was present in 98 out of 348 controls (28%). Also, the results of the Mantel-Haenszel test did not show a significant correlation [Mantel-Haenszel estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results suggest that TNFA (-308) alleles are not involved in the predisposition to the development of B-CLL.

Adult↗

HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis.

In the present study, two coding polymorphisms within the heat shock protein 70-hom gene (HSP70-hom) were analysed. One hundred and thirty-eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70-hom gene were typed using amplification refractory mutation system and polymerase chain reaction-restriction fragment length polymorphism technique, respectively. A significant prevalence of the HSP(+2437)-C allele and the HSP(+2437)-CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA-DRB1*03-positive patients with LS were carrying both HSP(+2437)-C and (+2763)-G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)-C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)-G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)-G allele was present with either DRB1*03 or HSP(+2437)-C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)-C and (+2763)-G in patients with LS. In conclusion, HSP(+2437)-C allele was found as a factor associating with susceptibility to sarcoidosis and LS.

Acute Disease↗

Use of handheld computers for assessment of prefrontal cortex function in patients with phenylketonuria.

Assessment of prefrontal brain cortex function can be helpful in treatment monitoring in patients with phenylketonuria. We aimed to assess the usefulness of computerized neuropsychological tests developed for handheld computers for this purpose. We observed worse test performance among persons with blood phenylalanine concentrations exceeding the recommended range. Use of handheld computers was assessed by patients and by doctors as interesting, not time-consuming and convenient. This method can be helpful during routine follow-up visits.

Adolescent↗

Residual protein levels on reprocessed dental instruments.

Reduction of the initial bioburden on instruments, prior to sterilization, is believed to reduce transmission risks of iatrogenic Creutzfeldt-Jakob disease. Endodontic files are used in the preparation of root canals and are likely to have close contact and become contaminated with neural material from branches of the maxillary and mandibular cranial nerves. This study examined methods used by 22 dental practices to clean endodontic files, and scored visible debris and residual protein levels adhering to 220 dental endodontic files that had been used, cleaned, autoclaved and were deemed ready for re-use. Visible debris was scored after examination under a dissecting light microscope. Residual protein was quantified using a fluorescent assay based on reaction of proteins with o-phthaldialdehyde/N-acetyl cysteine. There was wide variation in the methods used by practices to clean endodontic files. The cleaning process varied from a wipe with an alcohol-impregnated cloth to hand scrubbing and/or use of an ultrasonic bath. Surface debris was visually detected on 98% of files. Residual protein was detected on all the files examined (median amount: 5.4 microg; range: 0.5-63.2 microg). These results demonstrate that the cleaning of some instruments reprocessed routinely in primary care is incomplete, and such instruments cannot be excluded as a potential source of cross-infection.

Acetylcysteine↗

Negative feedback in NO/cGMP signalling.

Most of the effects of the signalling molecule nitric oxide (NO) are mediated by the stimulation of the NO-sensitive GC (guanylate cyclase) and the subsequent increase in cGMP formation. The enzyme contains a prosthetic haem group, which mediates NO stimulation. In addition to the physiological activator NO, NO-sensitizers like the substance YC-1 sensitize the enzyme towards NO and may therefore have important pharmacological implications. Two isoforms of NO-sensitive GC have been identified to date that share regulatory properties, but differ in the subcellular localization. The more ubiquitously expressed alpha1beta1 heterodimer and the alpha2beta1 isoform are mainly expressed in brain. In intact cells, NO-induced cGMP signalling not only depends on cGMP formation, but is also critically determined by the activity of the enzymes responsible for cGMP degradation, e.g. PDE5 (phosphodiesterase 5). Recently, direct activation of PDE5 by cGMP was demonstrated, limiting the cGMP increase and thus functioning as a negative feedback. As the cGMP-induced PDE5 activation turned out to be sustained, in the range of hours, it is probably responsible for the NO-induced desensitization observed within NO/cGMP signalling.

3',5'-Cyclic-GMP Phosphodiesterases↗

Patient education in inflammatory bowel disease does not influence patients knowledge and long-term psychosocial well-being.

BACKGROUND AND AIMS: Patient education is accepted in many disciplines as a valid component of disease management in chronic diseases. The aim of this prospective study was to analyze the effects of an education program in patients with inflammatory bowel disease. METHODS: 145 patients with inflammatory bowel disease were prospectively included: 73 were educated in four sessions, 72 were educated after the one year evaluation period (control group). The following topics were presented: pathogenesis, diagnostic procedures, course of disease, medical and surgical treatment, nutrition, social problems and support, stress management, and coping with the disease. RESULTS: The repeated measurement two-way analysis of variances showed no effects of the patient education program on disease-related knowledge, depression and quality of life. CONCLUSION: This patient education program was not able to increase disease-related knowledge or psychosocial variables in patients with IBD. However, most of the patients were very satisfied with the education program, since as judged by their own assessment it helped them to act responsibly for themselves and their disease.

Adolescent↗

Electrogastrography in neonates.

BACKGROUND AND AIMS: Procedures for diagnosis of gastrointestinal (GI) symptoms in newborn and preterm infants should preferably be non-invasive. This study evaluates the usability of electrogastrography (EGG), a non-invasive, cutaneous recording of the gastric myoelectrical activity in newborn infants. METHOD: Sixty-two randomly selected infants [27 girls and 35 boys with median gestational age of 36 weeks (range 29-42)] divided into six groups (by postconceptional age) were studied on median day 5 (range 1-24) after birth. None had GI symptoms. EGG recordings were made by Digitrapper EGG recording system. RESULTS: Findings were highly dispersed and without statistical difference both between pre- and postprandial periods and among the six study groups. Dominant frequency of 2.5 cycles per minute was found for 57 of 62 infants, with distribution of normal, bradygastric and tachygastric slow wave frequency uniformly dispersed around 50, 35 and 15% respectively. CONCLUSION: We find EGG unsuitable for clinical use because of significant variation in gastric slow wave frequency in normal term and preterm infants without GI symptoms.

Electrodiagnosis↗

Cemented titanium stems show high migration: transprosthetic drainage system has no advantage over third-generation cementation technique.

INTRODUCTION: A newly developed cemented titanium stem with excellent laboratory results using a transprosthetic drainage system (TDS) was clinically tried for the first time. Prognostic radiographic methods including migration measurement and clinical investigation were performed for up to 7 years. MATERIALS AND METHODS: Twenty-two patients prospectively and consecutively received total hip replacement using a cemented titanium stem and a threaded Zweymüller cup. Ten stems (CPS) were cemented conventionally with a third-generation cementation technique. In 12 stems (TRIOS) a TDS was used to enhance cement mantle quality. Design of cup and stem was similar in all cases. RESULTS: More than 50% of all stems showed considerable subsidence (>1 mm at 2 years and >2.5 mm at 5 years) and progressive radiolucent lines ( >1 mm at 2 years). Two patients of the TRIOS group had to be revised at 7 years postoperatively. No significant differences were found in radiological parameters (migration, stem subsidence, tilting, occurrence of radiolucent lines) and clinical outcome between the two cementation techniques. All parameters indicate an unfavourable long-term survival. Use of a TDS did not show any significant advantages over the conventional cementation technique. CONCLUSION: It can be concluded that cementing titanium stems of this design cannot be recommended.

Aged↗

An update of recent evidence of the relationship between objective and self-report measures of the physical environment and physical activity behaviours.

The physical environment has the potential to influence the physical behaviours of large numbers of people; hence creating supportive environments has the potential to increase physical activity (PA). During the last decade, there has been growing interest in how the physical environment shapes PA behaviour. This area of research is important given that levels of PA participation are declining globally. Literature was reviewed that examined the association between physical environmental attributes and PA behaviours. The environmental attributes were grouped into four categories based on a conceptual framework of environmental factors that might influence PA and included functionality, safety, aesthetics and destinations. Positive associations were found between both perceived and objectively measured environmental factors and PA behaviour. The availability, accessibility and convenience of destinations and facilities, as well as the general functionality of the neighbourhood (eg, the presence of sidewalks, traffic conditions) and aesthetics were positively associated with various levels of PA. The review highlights the need for future studies: to examine behaviour-specific environmental attributes, to collect objectively-measured environmental data and to include both objective and perceived environmental data in the same studies, and to adopt prospective study designs to allow causal relationships to be established.

Environment↗

Lack of IFN-gamma 2/2 homozygous genotype independently of recipient age and intensity of conditioning regimen influences the risk of aGVHD manifestation after HLA-matched sibling haematopoietic stem cell transplantation.

A total of 110 patients (71 adults and 39 children) who received allogeneic haematopoietic stem cell transplantation from HLA-matched sibling donors were studied for the incidence of acute graft-versus-host disease (aGvHD) in relation to IFN-gamma gene microsatellite polymorphism. A strong tendency was observed towards the lower incidence of grades II-IV aGvHD in patients having an IFN-gamma 2/2 genotype as compared to the recipients with other IFN-gamma genotypes (0.12 vs 0.33, P=0.06). This relationship was independent of the intensity of conditioning regimen and diagnosis. IFN-gamma polymorphic features, together with other clinical and biological factors (patient's age, donor-recipient gender, diagnosis, conditioning regimen, transplant material and GvHD prophylaxis), were subjected to multivariate analysis for aGvHD manifestation in order to exclude indirect association of the IFN-gamma 2/2 genotype. In multivariate analysis, myeloablative therapy (OR=11.462, P=0.013), recipient age (OR=4.896, P=0.009) and lack of IFN-gamma 2/2 genotype (OR=4.311, P=0.048) were found to significantly contribute to the development of grade II-IV aGvHD, while type of GvHD prophylaxis showed less-strong influence (OR=2.963, P=0.066). Thus, it appeared that the IFN-gamma 2/2 genotype constituted an independent and protective factor associated with a decreased risk of grade II-IV aGvHD. However, this genotype was not found to be associated with the risk of cGvHD or survival.

Acute Disease↗

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

Cerebral Palsy↗

Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients.

BACKGROUND: The reported probability of survival of patients with Hodgkin's disease (HD) following high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is 35-65% at 5 years. The Polish Lymphoma Research Group investigated retrospectively prognostic factors for overall survival (OS) and event-free survival (EFS), and the risk of secondary malignancies in a large series of patients who underwent HDC/ASCT. PATIENTS AND METHODS: The data of 341 consecutive patients treated in 10 centers from 1990 to 2002 were collected and analyzed. RESULTS: The actuarial 5-year OS and EFS were 64% [95% confidence interval (CI) 57% to 71%] and 45% (95% CI 39% to 51%), respectively. In the multivariate model, unfavorable prognostic factors for EFS were less than partial response at the time of ASCT [relative risk (RR), 2.92 (95% CI 1.68-5.08); P<0.001] and three or more previous chemotherapy lines (RR, 2.16; 95% CI 1.42-3.30; P<0.001). These two factors were also associated with unfavorable OS (RR, 3.32; 95% CI 1.90-5.79; P<0.001 and RR, 2.34, 95% CI 1.51-3.64; P<0.001). Five-year cumulative risk of secondary malignancy was 8.4% (95% CI 2% to 13%) and the only identified risk factor was splenectomy (P=0.02). CONCLUSIONS: HDC/ASCT should be considered early in the course of disease for patients with a response after standard therapy.

Adolescent↗

B-cell lymphoproliferative syndrome and peripheral blood CD20+ cells expansion after hematopoietic stem cell transplantation: association with fludarabine and anti-thymocyte globulin containing conditioning regimen.

Fifty-eight patients who received hematopoietic stem cell transplants during a 3-year period in our unit were followed for the symptoms of posttransplant B-cell lymphoproliferative syndrome (B-cell PTLD). Three cases showed lymph node enlargement; in 14, there was an excess of B cells in the blood. Histochemical staining of lymph nodes revealed CD20+ cell expansion in two cases, and in one, CD38+ and CD138+ cells. Kappa and lambda staining revealed poly- or oligoclonal expansion, which was characterized by the presence of Ki67+ cells in 10% to 50% of cells. In 14 cases, an excess of CD20+ cells were observed in blood. Clinical analysis revealed that patients with B-cell expansion in blood and/or in lymph nodes frequently showed fever and that some subjects displayed arthralgia, hemolytic anemia, and hepatitis. LMP-1-positive cells were observed in lymph nodes as well as EBV copies, whereas only a proportion of patients with the excessive CD20+ cells in blood were EBV positive. Notably, lymph node enlargement and CD20+ blood excess occurred significantly more frequently among patients receiving a Fludarabine (Flu) and anti-thymocyte globulin (ATG) conditioning regimen than those whose treatment lacked Flu independent of whether they received ATG (0.80 vs 0.44; P =.036).

Adult↗

HLA-DR11 in addition to donor age, gender, and major blood group incompatibility influence the incidence of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

The present study sought to retrospectively assess risk factors for occurence of and mortality from severe acute graft-versus-host-disease (aGvHD) among 66 patients receiving hematopoietic stem cell transplants (HSCT) from matched sibling donors (MSD). Thirty-six patients were in early and 30 in intermediate or advanced stages of the disease. Twenty-six patients developed severe aGvHD grades II-IV. Thirty-five patients died after transplantation (15 due to aGvHD). There were 20 major ABO-mismatched transplants and 26 cases wherein donor and recipient differed with respect to sex (11: F-->M; 15: M-->F). These transplant characteristics as well as HLA class II specificities were chosen for discriminative analysis. HLA specificities were assessed in an independent analyses for as patients lacking (DR11) or having DR13 associated with aGvHD. It appeared that donor age increased the risk of aGvHD, but a fatal outcome of this complication was influenced by recipient age. Female to male transplantations were associated with a higher risk of aGvHD. Major ABO incompatibility tended to increase the risk of aGvHD and fatal outcomes. DR11 was associated with factors playing a protective role, while DR13 was the least of all significant factors influencing the development of severe and fatal aGvHD.

ABO Blood-Group System↗

TNF polymorphisms are associated with toxic but not with aGVHD complications in the recipients of allogeneic sibling haematopoietic stem cell transplantation.

NcoI polymorphism within the promoter/enhancer region of TNFalpha and the first intron of TNFbeta encoding gene was analysed in 70 patients with haematological malignancies transplanted from HLA-identical sibling donors. The control group was composed of 130 healthy individuals. We showed that patients heterozygous for one or both TNF genes suffered more frequently from severe (grades III-IV) toxic complications than those carrying the other TNF genotypes (TNFA(*)1,2: 9/10 vs 30/60, P<0.05; TNFB(*)1,2: 20/26 vs 19/44, P<0.01; TNFA(*)1,2 TNFB(*)1,2: 9/9 vs 30/61, P<0.005). Conversely, patients having TNFB(*)2,2 less frequently presented with severe toxic lesions (17/39 vs 22/31, P<0.05). Additional analyses showed that TNFA(*)1,2, independent of the TNFB genotype composition, influenced the manifestation of grades III-IV toxic lesions, while TNFB(*)2,2 and TNFA(*)1,1 in combined association played a protective role. Logistic regression analysis confirmed the association of recipient TNFA(*)1,2 genotype with severe toxic complications, in addition to aggressive myeloablative conditioning regimen and female to male transplantation. No relation was found between TNF polymorphic features and aGvHD incidence by either uni- or multivariable analyses.

Adolescent↗

Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks' gestation.

AIM: There is a need for a rapid method to identify infants who will develop respiratory distress syndrome (RDS) soon after birth, to allow early treatment of affected infants with surfactant. The microbubble stability test (MST) may be one such method, but clinical experience is sparse. METHODS: The MST was performed on gastric aspirates from 188 infants with a mean gestational age of 29 (range 23-31) wk. RESULTS: 87 infants developed moderate to severe RDS, corresponding to a prevalence of 46%. The sensitivity, specificity and predictive values for identification of infants with moderate to severe RDS were determined for the average diameter of bubbles, the proportion of microbubbles with different diameters and the total number of microbubbles. The proportion of microbubbles with diameters <20 or 25 microm gave the best prediction, with a sensitivity of 78-79%, a specificity of 57-58%, a positive predictive value of 62% and a negative predictive value of 76%. Early treatment with nasal continuous positive airway pressure probably mitigated the development of RDS in some infants with a low-degree surfactant deficiency and this may explain the relatively low specificity. CONCLUSION: In infants of <32 wk gestation RDS can be predicted by computerized image analysis of the size distribution of microbubbles generated in gastric aspirates.

Gestational Age↗

Detection of disseminated epithelial cancer cells by liquid culture--factors interfering with the standardization of assays.

BACKGROUND: Immunocytochemistry is the standard method for detection of disseminated breast-cancer cells. Tumor-cell enrichment by cell culture has been used by several investigators, however assays published have not been well-standardized. METHODS: Breast-cancer cells from two lines were diluted in hemopoietic cells of varying origins and cultured in different media and different flasks. Factors influencing successful tumor-cell amplification by liquid culture were identified by investigation of 277 cultures. Parallel clinical samples, consisting of BM aspirations, leukapheresis samples and peripheral blood samples obtained from women with breast cancer, were investigated in 113 cultures. Cancer-cell detection by cell culture could be compared to immunocytochemistry in 101 cases. RESULTS: The frequency of tumor-cell detection was not improved by liquid culture, but a significant correlation between conventional tumor-cell detection and detection after liquid culture was found. Factors influencing tumor-cell amplification in the dilution assay could not be transferred to the investigation of clinical samples. It was concluded that culture-enrichment of disseminated cancer cells was very complex, and could be influenced by a variety of factors-even when a model system was used. DISCUSSION: It should be recognized that culture-enriched cancer cells probably represent a highly selected population of disseminated cancer cells, despite the significant correlation between tumor cells detected by conventional methods and following conventional methods after liquid culture. There is currently no evidence to suggest that cancer-cell amplification by cell culture could become a standardized technique for the detection of disseminated epithelial tumor cells.

Artifacts↗