EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.     

Short communication: treatment of relapsing-remitting multiple sclerosis 96 patients with IFN-beta1b: results of a 6-year follow-up.

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.     

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.     

Thoraxschmerz und Vorw?lbung der Thoraxwand

Ohne Zusammenfassung     

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.     

Invasive pneumococcal infections in Denmark from 1995 to 1999: epidemiology, serotypes, and resistance

Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.     

The anatomy of peripheral lymphoid organs with emphasis on accessory cells: Light-microscopic immunocytochemical studies of mouse spleen,lymph node,and peyer's patch

Antigen, lymphocytes, and accessory cells interact within peripheral lymphoid organs to generate immunity. Two cell types have been studied for accessory function in culture: mononuclear phagocytes and nonphagocytic Ia-rich dendritic cells. The monoclonal antibodies which have been used to study isolated murine macrophages (MØ) and dendritic cells (DC) include α-macrophage (F4/80, M1/70), α-dendritic cell (33D1), α-Fc receptor (2.4G2), and α-Ia (B21-2) reagents. In this paper, the antibodies have been used to stain accessory cells in cryostat sections of mouse spleen, lymph node, and Peyer's patch. Each organ is known to contain subregions that are rich in either macrophages, B cells, or T cells. We found that the accessory cells in each subregion had a different phenotype. (1) Macrophage-rich regions: Macrophages that lined the site of antigen delivery (marginal zone of spleen, around afferent lymphatics of node, and below the epithelium of Peyer's patch) were stained with M1/70 but not with F4/80. F4/80 was abundant on macrophages in other sites: spleen red pulp, node medulla, and around Peyer's patch efferent lymphatics. (2) B-lymphocyte-rich follicles: Follicular dendritic cells, which retain immune complexes extracellularly, are concentrated on the outer aspect of the germinal center. This region stained strongly with α-Fc receptor antibody 2.4G-2, but not with M1/70, F4/80, or 33D1. (3) T areas: The interdigitating cells of T areas have been linked to isolated dendritic cells. Irregular Ia-rich cells were distributed uniformly in the T areas of each organ. However, staining with 33D1 was not detected and was restricted to foci of nonphagocytic cells at the spleen red/white pulp junction. F4/80, M1/70 or 2.4G2 also did not stain the T area, except for the region close to splenic central arteries. Therefore the principal surface markers and location of the candidate accessory cells in murine lymphoid organs are M1/70⁺ macrophages at the site of antigen entry; F4/80⁺ macrophages around regions of lymphocyte efflux; germinal center dendritic cells, which may be rich in 2.4G2; and Ia-rich interdigiting cells in the T area.     

Investigations on the biology,epidemiology, pathology and control of<Emphasis Type="Italic"> Tunga penetrans</Emphasis> in Brazil: I. Natural history of tungiasis in man

Tungiasis is an important health problem in poor communities in Brazil and is associated with severe morbidity, particularly in children. The causative agent, the female flea Tunga penetrans, burrows into the skin of its host, where it develops, produces eggs and eventually dies. From the beginning of the penetration to the elimination of the carcass of the ectoparasite by skin repair mechanisms, the whole process takes 4-6 weeks. The present study is based on specimens from 86 patients, for some of whom the exact time of penetration was known. Lesions were photographed, described in detail and biopsied. Biopsies were examined histologically and by means of scanning electron microscopy (SEM). Based on clinical, SEM and histological findings, the "Fortaleza classification" was elaborated. This allows the natural history of tungiasis to be divided into five stages: (1) the penetration phase, (2) the phase of beginning hypertrophy, (3) the white halo phase, (4) the involution phase and (5) residues in the host's skin. Based on morphological and functional criteria, stages 3 and 4 are divided into further substages. The proposed Fortaleza classification can be used for clinical and epidemiological purposes. It allows a more precise diagnosis, enables the assessment of chemotherapeutic approaches and helps to evaluate control measures at the community level.     

Improved DOP-PCR-based representational whole-genome amplification using quantitative real-time PCR.

In many cases, only a minute amount of partially degraded genomic DNA can be extracted from archived clinical samples. Diverse whole-genome amplification methods are applied to provide sufficient amount of DNA for comparative genome hybridization, single-nucleotide polymorphism, and microsatellite analyses. In these applications, the reliability of the amplification techniques is particularly important. In PCR-based approaches, the plateau effect can seriously alter the original relative copy number of certain chromosomal regions. To eliminate this distorting effect, we improved the standard degenerate oligonucleotide-primed PCR (DOP-PCR) technique by following the amplification status with quantitative real-time PCR (QRT-PCR). With real-time detection of the products, we could eliminate DNA overamplification. Probes were prepared from 10 different tumor samples: primary and metastatic melanoma tissues, epidermoid and bronchioloalveolar lung carcinomas, 2 renal cell carcinomas, 2 colorectal carcinomas, and a Conn and Cushing adenoma. Probes were generated by using nonamplified and amplified genomic DNA with DOP-PCR and DOP-PCR combined with QRT-PCR. To demonstrate the reliability of the QRT-PCR based amplification protocol, altogether 152 relative copy number changes of 44 regions were determined. There was 85.6% concordance in copy number alterations between the QRT-PCR protocol and the nonamplified samples, whereas this value was only 63.8% for the traditional DOP-PCR. Our results demonstrate that our protocol preserves the original copy number of different chromosomal regions in amplified genomic DNA than standard DOP-PCR techniques more accurately.