Removable dental prostheses and cardiovascular survival: a 15-year follow-up study.

OBJECTIVES: In previous studies, increasing number of teeth predicted better survival and the acute needs for dental treatment predicted mortality. We sought to investigate whether restored dentitions by various removable dental prostheses impact cardiovascular (CVD) longevity. METHODS: Kuopio Oral Health and Heart study was initiated as a cross-sectional investigation with 256 subjects with diagnosed coronary artery disease [CAD] and 250 age- and sex-matched controls without CAD in 1995-1996. The mean age of both groups was 61, 30% were females. We appended mortality follow-up records to the baseline data and formulated this 15-year follow-up study. We examined the relationship between various types of dental prostheses and cardiovascular mortality by proportional hazard regression analyses. We also explored their correlation to oral and systemic inflammatory markers such as asymptotic dental score and C-reactive protein. RESULTS: In a model adjusted for age, sex and smoking, groups having only natural teeth (NT), removable partial denture(s) [PD] and NT, a PD and a full denture [FD], and FD/FD or FD/NT demonstrated the following hazard ratios for mortality (95% confidence interval). NT both arches: 1.00 [reference]; PD and NT: 0.75 [0.22-2.56]; PD and FD: 1.99 [1.05-3.81]; and FD opposed by FD or NT: 1.71 [0.93-3.13], respectively [p for trend=0.05]. Although statistically not significant, those with PD and NT with mean a number of teeth [Nteeth] of 15.4 had better survival compared with those who had all NT [Nteeth=22.5]; while those who had FD and PD [Nteeth=6.5] had shorter longevity than those with FD/FD or FD/NT [Nteeth=3.5]. CONCLUSIONS: Although not all subgroups of dental prostheses reached significant relationship with CVD mortality, our study suggests that not only the number [quantity] of remaining teeth but their maintenance [quality] removing potential inflammatory foci, such as pericoronitis or retained root tips, may positively impact on cardiovascular survival.

Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy.

BACKGROUND: The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. METHODS: Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. RESULTS: Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; P<0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P<0.01) and a reduction of 91% in the hazard of death (P<0.05). CONCLUSION: Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment.

[Performance of record linkage for cancer registry data linked with mammography screening data]. / Zur Leistungsfähigkeit des Record-Linkage zwischen epidemiologischen Krebsregistern und dem Mammographie-Screening.

The evaluation of the German Mammography Screening Program requires record linkage with data from cancer registries in order to measure the number of false-negative mammograms and interval cancers. This study aims at evaluating the performance of the established linkage method based on identifiers encrypted by the standard procedure of the German cancer registries. In addition, the results are compared with an alternative method based on plain text identifiers. A total of 16,572 records from the Bremen Mammography Screening Pilot Study were linked with data from the Bremen Cancer Registry. Based on a gold standard set of matching record pairs, homonym and synonym errors were determined. Given the customary threshold value in cancer registries, the plain text method showed a lower rate of synonym errors (2.1-5.1%) and a lower rate of homonym errors (0.01-0.15%). As 10.4 million women are invited to take part biennially in screening, the corresponding figures would be 3,237 homonym errors for the standard procedure and 294 using the plain text method provided equivalent conditions. The 11-fold increase in the homonym error rate documents the trade-off for better data protection using encrypted data.

Changes in cross-sectional area of spinal canal and vertebral body under 2 years of teriparatide treatment: results from the EUROFORS study.

The treatment of osteoporotic patients with teriparatide is associated with a significant increase in bone formation and gain of bone mass. The purpose of this post hoc analysis was to determine if the cross-sectional area (CSA) of the spinal canal and the vertebral body is affected by teriparatide treatment. Narrowing of the spinal canal might represent a safety problem, while widening of the vertebral CSA might improve mechanical stability. High-resolution computed tomography (HRCT) scans of vertebra T12 were obtained at baseline and after 6, 12, and 24 months of teriparatide treatment (20 microg/day) from 44 postmenopausal women with established osteoporosis participating in the prospective, randomized EUROFORS study. The CSA of the spinal canal did not decrease but increased marginally by 0.9% (2.6 mm(2)) over 24 months (P < 0.001), with a range from -0.5% (-2 mm(2)) to 3.1% (+8 mm(2)). Even when analyzing the spinal CSA on a slice-by-slice basis, no clinically relevant narrowing of the spinal canal was observed. For vertebral bodies, the CSA increased by 0.7% (5.7 mm(2)) over 24 months (P < 0.001), with a range from -0.4% (-3 mm(2)) to 1.6% (+14 mm(2)). Our data do not provide evidence for safety concerns regarding spinal canal narrowing. On the other hand, the increases observed for vertebral CSA apparently also only minimally contribute to the mechanical strengthening of the vertebral body under teriparatide treatment.

Development of anti-CD30 radioimmunoconstructs (RICs) for treatment of Hodgkin's lymphoma. Studies with cell lines and animal studies.

OBJECTIVES: Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. METHODS: The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with (111)In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radioimmunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with (131)I- Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. ((131)I-Ki-4, (131)I-5F11, (111)In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. RESULTS: All the RICs were successfully labelled with high specific activities (28-47 TBq/mmol) and sufficient radiochemical yields (>80%). Scatchard plot analysis proved high tumour affinity (KD = 20-220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (%ID/g) lay between 2.6 ((131)I-5F11) and 12.3 % ID/g ((131)I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. CONCLUSIONS: In-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates.

Biosolid and alum effects on runoff losses during turfgrass establishment.

Large, volume-based rates of composted biosolids (CB) enhance turfgrass establishment and soil properties, but nonpoint-source runoff losses could occur during production and after transplanting of sod. The objective was to evaluate runoff losses of N, P, sediment, and organic C during establishment of sprigs or transplanted sod of Tifway bermudagrass (Cynodon dactylon L. Pers. X C. transvaalensis Burtt-Davey) with and without CB and aluminum sulfate (Alum). Four treatments comprised Tifway sprigged in a sandy loam soil with and without incorporation of 0.25 m(3) CB m(-3) soil and Alum. In four additional treatments, sod transplanted from Tifway grown with and without CB was established with and without a surface spray of Alum. During early establishment, CB incorporated in soil before sprigging reduced runoff loss of sediment and total N to amounts comparable to transplanted sod. In contrast, mean runoff losses of total dissolved P and soluble-reactive P (SRP) were more than 50% greater for CB-amended sod than for fertilizer-grown sod or Tifway sprigged in soil with or without CB. Yet, the surface spray of Alum reduced runoff loss from sod more than 88% for SRP and 41% for dissolved organic C. Both surface sprays and incorporation of Alum effectively reduced SRP runoff loss from CB, soil, and turfgrass sources during turfgrass establishment.

Parentage analysis and outcrossing patterns in cacao (Theobroma cacao L.) farms in Cameroon.

The present study investigates the parentage of farm accessions in Cameroon using data from 12 microsatellite loci. Bayesian analysis suggests that 25.5% of the 400 farm accessions studied is still closely related to the traditional Amelonado variety called 'German Cocoa' by the farmers. Another 46.3% of the farm accessions were found to be direct descendants (20.8% first-generation (F1) hybrids and 25.5% selfed genotypes) from 24 parental clones used in biclonal seed gardens (BSGs) established in the 1970s in southern and western Cameroon. Furthermore, 28.3% of farm accessions appeared to descent from uncontrolled pollination events in cacao farms, which could be related to a common practice of cacao growers to use seeds collected in their own farm for new plantings. All farm accessions descending from BSG could be individually related through parentage analysis to the 24 progenitors of the BSG. Only 25% of progenies distributed from BSG corresponded to F1 hybrids combinations originally planned to be released. Significant biparental inbreeding estimates were observed for all 'traditional' farms and for most 'F1 hybrids' farms due to presence of a high proportion of selfed accessions. Biparental inbreeding occurs when plants receive pollen from genetically related neighbors. High levels of outcrossing observed in 'mixed' farms might be explained by the admixture of traditional varieties and BSG progenies. The implications of our finding for management of seed gardens and for further breeding using farm accessions in Cameroon are discussed.

Development of a marker assisted selection program for cacao.

ABSTRACT Production of cacao in tropical America has been severely affected by fungal pathogens causing diseases known as witches' broom (WB, caused by Moniliophthora perniciosa), frosty pod (FP, caused by M. roreri) and black pod (BP, caused by Phytophthora spp.). BP is pan-tropical and causes losses in all producing areas. WB is found in South America and parts of the Caribbean, while FP is found in Central America and parts of South America. Together, these diseases were responsible for over 700 million US dollars in losses in 2001 (4). Commercial cacao production in West Africa and South Asia are not yet affected by WB and FP, but cacao grown in these regions is susceptible to both. With the goal of providing new disease resistant cultivars the USDA-ARS and Mars, Inc. have developed a marker assisted selection (MAS) program. Quantitative trait loci have been identified for resistance to WB, FP, and BP. The potential usefulness of these markers in identifying resistant individuals has been confirmed in an experimental F(1) family in Ecuador.

Application of the use of high-throughput technologies to the determination of protein structures of bacterial and viral pathogens.

The Structural Proteomics In Europe (SPINE) programme is aimed at the development and implementation of high-throughput technologies for the efficient structure determination of proteins of biomedical importance, such as those of bacterial and viral pathogens linked to human health. Despite the challenging nature of some of these targets, 175 novel pathogen protein structures (approximately 220 including complexes) have been determined to date. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens.

[Secondary malignancies after successful primary treatment of malignant Hodgkin's lymphoma]. / Sekundärneoplasien nach erfolgreicher Primärtherapie des malignen Hodgkin-Lymphoms.

Malignant Hodgkin's lymphoma (HL) has become a curable disease through the increasing intensity of the treatment strategies applied. These regimens are aggressive, including radiotherapy and chemotherapy leading to the possibility of secondary malignancies. The German Hodgkin Lymphoma Study Group considered three cohorts including 5,411 patients with all stages of HL. In 127 patients a secondary solid tumor was diagnosed (cumulative risk 2%, median follow-up 72 months), with bronchial carcinomas (23.6%) and colorectal adenocarcinomas (20.5%) being the most frequent neoplasms. Secondary acute myeloid leukemia was found in 36 patients, another ten developed myeloid dysplasia (cumulative risk 1%, median follow-up 55 months). A total of 52 patients revealed a non-Hodgkin's lymphoma (NHL; cumulative risk 0.9%, median follow-up 46 months). The overall incidence of secondary malignancies was 3.9% in patients who had been treated successfully for their HL with radio- and/or chemotherapy.A secondary NHL can be particularly difficult to be distinguished from the preceding HL. Therefore, in case of a suspected relapse, a complete histopathological work-up must be performed.

[Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives]. / Radioimmuntherapie mit 90Y-markiertem Ibritumomab-Tiuxetan: Klinik, Radiopharmazie, Strahlenschutz, Perspektiven.

90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

Immunotherapy of Hodgkin's lymphoma.

Many new treatment approaches have given promising results in experimental Hodgkin's lymphoma (HL) models. Early clinical trials evaluating antibody based compounds as immunotoxins (ITs), radioimmunotherapy (RIT), bispecific molecules (BSMs), and recently monoclonal antibodies (MAbs), have demonstrated some clinical efficacy in patients with advanced refractory or relapsed HL. In addition, cellular immunotherapy is evolving. Although it seems unlikely to cure chemotherapy resistant patients with larger tumor masses by either of these approaches alone, the combination with conventional chemotherapy might help to overcome resistance of Hodgkin-/ReedSternberg (H-RS) cells. Another rationale for the development of these immunotherapies is to eliminate residual disease and thereby to prevent relapses from the disease. Currently, several clinical studies are running. A murine MAb (Ki-4) based 131 Iodine conjugate has shown efficacy in refractory HL patients in a phase II study, but less toxic constructs using alternate MAbs or isotopes should be developed. A humanized as well as a fully human anti-CD30 MAb are being tested in clinical phase I/II studies. These MAbs could engage the human immune system against the H-RS cells. In addition, these MAbs could be then combined with conventional chemotherapy in order to improve the treatment of HL.

A dominant linear B-cell epitope of ricin A-chain is the target of a neutralizing antibody response in Hodgkin's lymphoma patients treated with an anti-CD25 immunotoxin.

Hodgkin's lymphoma patients treated with an anti-CD25 Ricin toxin A-chain (RTA)-based Immunotoxin (RFT5.dgA) develop an immune response against the toxic moiety of the immunoconjugate. The anti-RTA antibody response of 15 patients showing different clinical features and receiving different total amounts of RFT5.dgA was therefore studied in detail, considering antibody titre, IgG and IgM content, average binding efficacy and ability to inhibit in vitro the cytotoxicity of a RTA-based Immunotoxin. No correlations were found between these parameters and the clinical features of the patients or the total amount of Immunotoxin administered. However, using a peptide scan approach we have identified a continuous epitope recognized by all patients studied, located within the stretch L161-I175 of the RTA primary sequence, close to a previously identified T-cell epitope. The ability of anti-L161-I175 antibodies to recognize folded RTA and to affect the biological activity of RTA by inhibiting RTA-IT cytotoxicity in vitro revealed that they may exert an important role in IT neutralization in vivo. Discovery of RTA immunodominant epitopes which are the target of anti-RTA immune response may lead to the development of immunomodulating strategies and to more successful treatment schedules.

[Why are babies born at night at increased risk of early neonatal mortality?]. / Warum ist die Sterblichkeit von nachts geborenen Kindern erhöht?

BACKGROUND: Increased perinatal and neonatal mortality rates have been previously reported in night-time births compared with births during the day. This effect has been attributed to decreased quality of medical care during the night. However, alternative explanations exist such as decreased birth-weight of night births. The objective of this study was to further investigate this relationship. MATERIALS AND METHODS: Data from 590,332 low risk births (singleton births, > or = 2500 g birth-weight, no major congenital anomaly) were obtained from the perinatal birth register of Hesse, Germany, 1990-2000. Outcome was defined as either death during labour or within 7 days of life. Night-time births were defined as births between 9.00 p.m. and 6.59 a.m., otherwise day-time births were assumed. Subgroup analyses and logistic regression analyses were performed to assess whether the excess mortality of night-births might be explained by other factors. RESULTS: Mortality rates were increased in night-time births (RR = 1.26; 95% CI = 0.94-1.70). This relationship was more pronounced in spontaneous births (RR = 1.58; 95% CI = 0.96-2.61) and emergency cesarean sections (RR = 1.76; 95% CI = 1.10-2.82). Significance persisted after adjusting for numerous potential confounders. CONCLUSION: Our results confirm an increased mortality risk for night-time births which could not be explained by other accessible risk factors. This suggests that the increased risk at night might be attributable to a reduced availability to provide appropriate medical care in delivery units at night. DISCUSSION: As mainly the presence of staff is decreased during the night, introduction of better designed shifts can be expected to reduce neonatal mortality.

[Umbilical blood pH, Apgar scores, and early neonatal mortality]. / Nabelschnurarterien-pH, APGAR-Scores und frühe neonatale Mortalität.

BACKGROUND: For several decades Apgar scores and umbilical blood pH sampling have been routinely used in the assessment of newborns. The aim of this study was to examine the prognostic value of neonatal survival using population-based data and to put these analyses into context with international studies. MATERIAL AND METHODS: Data from 513,135 live births from the Perinatal Birth Register of Hesse, 1990 - 1999, were used. Death in the first week of life (early neonatal death) was used as endpoint of analyses. Receiver operator characteristic analyses were employed to compare the prognostic value of Apgar scores and umbilical blood pHs independently of cutoffs used. RESULTS: Scores and umbilical blood pH showed a strong association with early neonatal morality. The relative risk of early neonatal mortality in term infants with scores 0 - 3 yields a relative risk of 1193 (95 % confidence interval = 801 - 1778) compared with babies born with scores 7 - 10. Scores at 1, 5, and 10 minutes were superior in predicting early neonatal mortality compared to umbilical blood pH, independent of cutoffs used. CONCLUSIONS: Scores remain essential in the prediction of early neonatal survival. Umbilical blood pH is also strongly and significantly associated with early neonatal death, even though it is much less pronounced than the score. DISCUSSION: The poor mortality prediction of umbilical blood pH sampling in Hesse compared with umbilical blood pH sampling in a large American delivery unit with a highly standardized measuring routine may be explained by a lower proportion of extremely acidotic infants or may be attributable to a decreased proportion of or to a less unified or less reliable measurement of the umbilical blood pH in Hesse.

Resistance gene homologues in Theobroma cacao as useful genetic markers.

Resistance gene homologue (RGH) sequences have been developed into useful genetic markers for marker-assisted selection (MAS) of disease resistant Theobroma cacao. A plasmid library of amplified fragments was created from seven different cultivars of cacao. Over 600 cloned recombinant amplicons were evaluated. From these, 74 unique RGHs were identified that could be placed into 11 categories based on sequence analysis. Primers specific to each category were designed. The primers specific for a single RGH category amplified fragments of equal length from the seven different cultivars used to create the library. However, these fragments exhibited single-strand conformational polymorphism (SSCP), which allowed us to map six of the RGH categories in an F(2) population of T. cacao. RGHs 1, 4 and 5 were in the same linkage group, with RGH 4 and 5 separated by less than 4 cM. As SSCP can be efficiently performed on our automated sequencer, we have developed a convenient and rapid high throughput assay for RGH alleles.

Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma.

BACKGROUND: Immunotoxins (ITs) consist of cell binding ligands coupled to toxins or their subunits. Hodgkin's lymphoma (HL) is an excellent target for ITs since lymphocyte activation markers such as CD25 and CD30 are expressed in large numbers. The ITs RFT5.dgA (anti CD25) and Ki-4.dgA (anti CD30) were constructed by linking the monoclonal antibodies RFT5 and Ki-4 to deglycosylated ricin A-chain (dgA). Both ITs showed potent specific activity against HL cells in vitro and in vivo in animal models, and were subsequently evaluated in phase I/II clinical trials in humans. PATIENTS AND METHODS: In two separate trials, the ITs were administered i.v. four times every other day over 4 h. The objectives of the phase I trials included the determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, antitumor activity and immune response against the IT. RESULTS: Twenty-seven patients with refractory HL were included in the phase I/II study of RFT5.dgA and 17 patients were included in the phase I study of Ki-4.dgA. The MTD of RFT5.dgA was 15 mg/m(2), whereas that of Ki-4.dgA was 5 mg/m(2). DLTs were related to vascular leak syndrome, consisting of edema, tachycardia, dyspnea, weakness and myalgia. Measurement of serum levels of RFT5.dgA demonstrated a C(max) of 0.2-9.7 micro g/ml with a half-life (t()) varying from 4 to 10.5 h. Peak serum concentration of Ki-4.dgA ranged from 0.23 to 1.7 micro g/ml. In both trials approximately 60% of patients developed human anti-mouse and/or anti-dgA antibodies. Seventeen of 18 patients treated at the MTD of RFT5.dgA were evaluable for clinical response. Responses included two partial remissions (PR), one minor response (MR) and five stable diseases (SD). Fifteen of 17 patients treated with Ki-4.dgA were evaluable for clinical response. Responses included one PR, one MR and two SD. CONCLUSIONS: RFT5.dgA and Ki-4.dgA showed moderate efficacy in heavily pretreated refractory patients with HL. Ki-4.dgA was less well tolerated than RFT5.dgA. This might be due, at least in part, to the formation of Ki-4.dgA/sCD30 complexes.

[Assessing the impact of delivery unit size on neonatal survival: estimation of potentially avoidable deaths in Hessen, Germany, 1990-2000]. / Hat die Grösse der Geburtsklinik Einfluss auf das neonatale Uberleben? Schätzung von "vermeidbaren" Todesfällen in Hessen 1990-2000.

BACKGROUND AND OBJECTIVE: There are only few analyses from Germany on the impact of delivery unit size on neonatal outcome. The objective of this study was to evaluate the influence of delivery unit size on neonatal survival in Germany. PATIENTS AND METHODS: Data from the perinatal birth register for Hessen for 1990-2000 comprising 640554 births, and the Neonatal Survey for 1989-1997 in Hessen were used. Potentially avoidable deaths were assessed according to delivery unit size and birth weight category. Additionally trend analyses and an extrapolation to potentially avoidable deaths in all of Germany were performed. RESULTS: Compared to large delivery units, smaller ones showed higher risk adjusted mortality rates. Calculation of potentially avoidable deaths gave an estimate of 257 early neonatal deaths in 11 years. Although trend analyses revealed a decline of potentially avoidable deaths, an extrapolation of such deaths for all of Germany still yielded an estimate of more than 300 potentially avoidable deaths per year using data from 1997-2000 only. CONCLUSION: A valid inference as to the magnitude of the observed effect remains even in the face of a very cautious interpretation of our results. During the study period of 11 years, more than 200 neonatal deaths could be attributed to the fact that births in Hessen are dispersed among many small hospitals. If this pattern of births in small units is common throughout Germany, it suggests that several hundred neonatal deaths per year may be attributed to this risk factor when extrapolating these results nationally. Further research is necessary to describe the nation-wide magnitude of this problem and to identify the role of underlying causal risk factors more precisely. Additionally policy discussions regarding structural changes in obstetrical care should be undertaken in the meantime, aimed at reducing the observed mortality rates.

[Hodgkin's lymphoma in nuclear medicine: diagnostic and therapeutic aspects]. / Nuklearmedizinische Aspekte in der Diagnostik und Therapie des Hodgkin-Lymphoms.

Today, diagnostic and therapeutic strategies of Hodgkin lymphoma (HL) with positron emission tomography and radioimmunotherapy include state-of-the-art nuclear medicine which require the cooperation between oncology and nuclear medicine. The benefit of FDG-PET in HL patients with residual tumor masses consists of its high negative predictive value in the therapy control of the disease. The concept of waitful watching in patients with PET-negative residual masses after BEACOPP-chemotherapy will be evaluated in a large multicenter trial of the GHSG (German Hodgkin Study Group). Radioimmunotherapy has been performed in patients with CD20-positive Non-Hodgkin lymphoma for 10 years with promising results. HL is also an excellent target for immunotherapy due to the expression of antigens such as CD25 and CD30. Thus, a new radioimmunoconstruct consisting of the murine anti-CD30 antibody Ki-4 labeled with iodine-131 was developed for patients with relapsed or refractory HL.

Mitochondrial DNA restriction map for the Caribbean fruit fly, Anastrepha suspensa, and occurrence of mitochondrial DNA diversity within highly inbred colonies.

A restriction map has been constructed for Anastrepha suspensa mitochondrial DNA. One HaeIII site was found to be polymorphic among individuals in highly inbred colonies and a feral population. Based on mapping information, the polymorphic site was determined to be in the ATPase 6 gene. Primers TK-J-3804 and C3-N-5460 amplified this region. The amplicon was cut by HaeIII in flies of one haplotype and not cut in flies of the other haplotype. From 30 to 43% of the individual flies studied had this additional HaeIlI site. After cloning of the approximately 5200 bp XbaI fragment, the two mitotypes were identified. A 988 base fragment, coding for the entire tRNA-Lys(AAG), tRNA-Asp(GAC), and ATPase 8genes, and a partial ATPase 6gene was sequenced Four silent mutations, including the one at the informative site were located. The HaeIII polymorphism and other sequence differences may prove useful as a diagnostic for identification of the origin of introduced fruit flies.