In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39 weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67-1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

[Case report of an osseous (and lymphogenic) thymic carcinoma in an adult]. / Kasuistik eines ossär (und lymphogen) metastasierten Thymuskarzinoms beim Erwachsenen.

A Thymic carcinoma in adults is rare. We present the case of a 47-year-old man, who was treated conservatively for spondylolisthesis L5/S1 in our institution for several years. In the further course, the patient complained about pain exacerbation with acute lower back pain. Cross-sectional scanning showed a tumor of the lumbar vertebral body three. A biopsy of this mass revealed a metastatic thymic carcinoma of the squamous cells. After palliative therapy, the patient died 9 months after initial diagnosis.

Structure property relationships affecting the proton conductivity in imidazole loaded Al-MOFs.

The structures of the imidazole loaded derivatives of Al-MIL-53 [Al(OH)(1,4-BDC-(CH3)x)] (x = 0, 1, 2) and CAU-11 ([Al(OH)(SDBA)]) (1,4-H2BDC = terephthalic acid; H2SDBA = 4,4'-sulfonyldibenzoic acid) were determined from powder X-ray diffraction data. Impedance spectroscopy measurements were carried out to evaluate their proton conductivities under anhydrous conditions at temperatures up to 110 °C. In Al-MIL-53-(CH3)x_HIm (x = 0, 1, 2) the formation of hydrogen bonds between the framework and the guest molecules results in a decrease in proton conductivity (x0 = 1.7 × 10-6, x1 = 1.9 × 10-8 and x2 = 1.7 × 10-9 S cm-1 at 110 °C and Eact = 0.42, 0.41 and 0.46 eV, for 0, 1 and 2 CH3-groups, respectively). The highest conductivity has been measured for CAU-11_HIm with 3.0 × 10-4 S cm-1 at 110 °C (Eact = 0.19 eV), where no host-guest hydrogen bonding interactions are observed.

Free radical release and HSP70 expression in two human immune-relevant cell lines after exposure to 1800 MHz radiofrequency radiation.

The goal of this study was to investigate whether radiofrequency (RF) electromagnetic-field (EMF) exposure at 1800 MHz causes production of free radicals and/or expression of heat-shock proteins (HSP70) in human immune-relevant cell systems. Human Mono Mac 6 and K562 cells were used to examine free radical release after exposure to incubator control, sham, RF EMFs, PMA, LPS, heat (40 degrees C) or co-exposure conditions. Several signals were used: continuous-wave, several typical modulations of the Global System for Mobile Communications (GSM): GSM-non DTX (speaking only), GSM-DTX (hearing only), GSM-Talk (34% speaking and 66% hearing) at specific absorption rates (SARs) of 0.5, 1.0, 1.5 and 2.0 W/kg. Heat and PMA treatment induced a significant increase in superoxide radical anions and in ROS production in the Mono Mac 6 cells when compared to sham and/or incubator conditions. No significant differences in free radical production were detected after RF EMF exposure or in the respective controls, and no additional effects on superoxide radical anion production were detected after co-exposure to RF EMFs+PMA or RF EMFs+LPS. The GSM-DTX signal at 2 W/kg produced a significant difference in free radical production when the data were compared to sham because of the decreasing sham value. This difference disappeared when data were compared to the incubator controls. To determine the involvement of heat-shock proteins as a possible inhibitor of free radical production, we investigated the HSP70 expression level after different RF EMF exposures; no significant effects were detected.

Hsp70 expression and free radical release after exposure to non-thermal radio-frequency electromagnetic fields and ultrafine particles in human Mono Mac 6 cells.

The contemporary urban environment has become increasingly complex in its composition, leading to discussions regarding possible novel health effects. Two factors that recently have received considerable attention are ultrafine particles (UFP; <0.1 microm) produced by combustion processes and emissions from wireless communication devices like mobile phones that emit in the radio-frequency (RF) part of the spectrum. Several studies have shown biological effects of both these exposures in various cell systems. Here we investigate if exposure to UFP (12-14 nm, 100 microg/ml) and RF-electromagnetic fields (EMF; 2 W/kg specific absorption rate (SAR); continuous wave (CW) or modulated (217Hz or GSM-nonDTX)), alone or in combination influences levels of the superoxide radical anion or the stress protein heat-shock protein (Hsp70) in the human monocyte cell line Mono Mac 6. Heat treatment (42-43 degrees C, 1h) was used as positive control for both stress reaction and for heat development in the RF exposure setup. Our results clearly show that Mono Mac 6 cells are capable to internalise UFP, and that this phagocytic activity is connected to an increased release of free radicals. This increase (40-45% above negative control) is stronger than the effect of heat treatment. On the other hand, none of the employed RF exposures showed any effects on free radical levels. Co-exposure of RF and UFP did not potentiate the UFP effect either. Our investigations showed a significantly increased Hsp70 expression level by heat treatment in a time-dependent manner, whereas UFP, RF, or UFP+RF were without any effect. Therefore, we conclude that in the investigated Mono Mac 6 cells, RF exposure alone or in combination with UFP cannot influence stress-related responses.

[Improvement of protection given by vaccination for socially underprivileged groups on the basis of "key persons approach" -- results of an intervention based on cultural and language aspects for children of immigrants in Altlander Viertel provided by the Health Department of Stade]. / Verbesserung des Impfschutzes für sozial benachteiligte Gruppen unter Mitarbeit von Vertrauenspersonen - Ergebnisse einer kultur- und sprachsensiblen Intervention des Gesundheitsamtes Stade und des Ethno-Medizinischen Zentrums für Migrantenkinder im Altländer Viertel.

In January 2002, a vaccination campaign against measles, mumps and rubella was carried out in the Altlander Viertel, a district in Stade, Germany. The campaign was directed towards children of immigrants, a group often at a disadvantage in terms of health. This campaign was organised and carried out by the public health department in Stade for the first time in September 2002. During regular health screenings when children were enrolled for school it was found that they children were poorly protected by vaccination against measles, mumps and rubella. Since several attempts to improve the situation, for example by organising information events, had not been successful, it was decided to develop special measures for this particular group in order to improve their health. Together with the Ethno-Medical Centre in Hanover the concept of a vaccination campaign considering the special situation of immigrants was developed. The core measures were to find, train and use key persons within the groups of immigrants are living in the Altlander Viertel in Stade. These key persons helped to inform and motivate the immigrants to go to the vacciantion stations set up in the district. In this way it was possible to carry out a successful intervention (vaccination campaign).

[Improved osseointegration of titanium implants of different surface characteristics by the use of bone morphogenetic protein (BMP-3): an animal study performed at the metaphyseal bone bed in dogs]. / Verbesserte Osseointegration von Titanprüfkörpern unterschiedlicher Oberflächenbeschaffenheit durch Beschichtung mit Bone Morphogenetic Protein (BMP-3)--eine tierexperimentelle Studie im metaphysären Knochenlager des Hundes.

AIM: Aim of this study was to determine whether coating of titanium implants of various surfaces with BMP-3 would improve the osseous integration of the implants into the orthotopic bony implant bed. METHOD: In this experimental study 190 micro g per implant of highly purified bone morphogenetic protein 3 (BMP-3) precipitate isolated from porcine bone were available for the coating of each of 24 cylindrical test implants (12 with hydroxyapatite and 12 with plasmapore surface). The remaining 24 test implants with the same surface makeup served as negative controls. Implantation sites were randomly assigned for the 4 versions of implants available and all implants were embedded into the medial or lateral femoral condyle of both legs of 12 German shepherds. The drilling holes were performed in such a matter that after embedding the cylindrical devices a gap of 1 mm surrounding the implants remained. A biomechanical testing and histological evaluation was performed on the explants 42 days after surgery. RESULTS: In biomechanical testing forces necessary to extract the implants from the explanted bones in BMP-3 coated devices were up to 70% higher compared to the ones in the non-coated reference groups. Quantitative histomorphometric examination showed in BMP-3-coated implants an increasing formation of new bone close to their own surface (gap-healing) which was higher than in the corresponding non-coated controls (hydroxyapatite + BMP-3 32.1%, hydroxyapatite controls 20.3%, plasmapore + BMP-3 30.2%, plasmapore controls 13.1%). The extent of direct bone implant contact as percentiles of the corresponding implants perimeter (ongrowth) was also significantly higher in the BMP-3-coated implants compared to the non-coated controls (hydroxyapatite + BMP-3 37.7%, hydroxyapatite controls 22.4%, plasmapore + BMP-3 15.3%, plasmapore controls 6.4%). CONCLUSION: In this study it was proven the first time that implants of various surface textures as used in endoprosthetics are able to be coated by the osteoinductive growth factor BMP-3. In that way metallic implants can achieve osteogenic properties which have positive effects in osseointegration.

[Histologic and histomorphometric follow-up observations of osseointegration of corundum-blasted BMP-3 coated titanium test implants (Ti6Al4V) at orthotopic site in the giant rabbit]. / Histologische und histomorphometrische Verlaufsbeobachtungen zur knöchernen Integration von korund-gestrahlten BMP-3-beschichteten Titanprüfkörpern (Ti-6Al-4V) im orthotopen Lager des Riesenkaninchens.

AIM: To establish whether the additional coating of titanium implants with Bone Morphogenetic Protein-3 (BMP-3) might enhance osseous integration. METHOD: Each of 15 cylindrical titanium test implants (Ti-6AI-4V) was coated using 230 micrograms porcine BMP-3. A further 15 implants with identical (corundium-blasted) surface served as negative controls. An uncoated and a BMP-3-coated test object were implanted into the femurs of 15 adult giant rabbits. New formation of bone around the implants was examined microscopically and histomorphometrically on postoperative days 14, 35 and 56. RESULTS: Coated implants revealed superior osseointegration with statistical evaluation using the t-test for matched samples showing a significantly higher volume of new bone 5 weeks after surgery. Microscopic examination revealed osseointegration with no connective tissue membrane around the surface of the implants. CONCLUSIONS: Our results indicate that composite metal implants are suitable carriers for BMP-3 and that improved fixation of the implants can be achieved.

Immunological detection of Nitrospira-like bacteria in various soils.

Chemolithotrophic nitrite oxidizers were enriched from five different soils including freshwater marsh, permafrost, garden, agricultural, and desert soils and monitored during the cultivation procedure. Immunoblot analysis was used to identify the nitrite oxidizing organisms with monoclonal antibodies, which recognize the key enzyme of nitrite oxidation in a genus-specific reaction [Bartosch et al. (1999) Appl Environ Microbiol 65:4126-4133]. The morphological characteristics of the enriched nitrite oxidizers were additionally studied using transmission electron microscopy (TEM) and fluorescence microscopy. By means of the antibodies and TEM analysis Nitrospira could be clearly identified in enrichment cultures derived from freshwater marsh and from permafrost soil. Nitrospira cells were enriched simultaneously with cells of the genus Nitrobacter when nitrite concentrations of 0.2 g of NaNO2 L(-1) were used. However, in enrichment cultures containing 2 g of NaNO2 L(-1) Nitrobacter was exclusively detected. During fluorescence microscopic observations of DAPI stained samples microcolonies were found in enrichment cultures from freshwater marsh, permafrost, garden, and agricultural soil. They had a similar morphology to Nitrospira-like microcolonies from activated sludge. In conclusion, Nitrospira seems to be not only a common aquatic but also a usual soil bacterium.

[Osteogenetic activity of BMP-3-coated titanium specimens of different surface texture at the orthotopic implant bed of giant rabbits]. / Osteogene Aktivität BMP-3-besichichteter Titanprüfkörper unterschiedlicher Oberflächenbeschaffenheit im orthotopen Lagen des Riesenkaninchens.

INTRODUCTION: The successful combination of osteoinductive factors with current materials used in both endoprosthetics and implantology improves bony ingrowth and long-term stability of the chosen implants. The aim of the present experimental animal study was to clarify in what way faster bony integration can be achieved through additional BMP-3-coating of titanium test implants of different surface textures (hydroxy-apatite-coated or corundum-blasted). METHODS: Thirty of 60 cylindrical titanium test implants with a hydroxy-apatite or corundum-blasted surface were coated with 230 microg porcine, high-purified BMP-3-precipitate per implant to check their osteoinductive potential in a bioassay. In each case a BMP-3-coated and an uncoated control-device were implanted with a gap formation of 1 mm into the femoral part of the patellofemoral joint of the right and left leg of 30 adult giant rabbits. Serial saw slices of all explanted specimens were prepared, and the osseous integration of the implant and time-dependent bone neoformation were analyzed microscopically and histomorphometrically 14, 35, and 56 days after implantation. RESULTS: Coating of TiAl4V6-test devices with BMP-3 led in both groups after gap implantation to an improved osseointegration, that was histomorphological and histomorphometrical verifiable. Statistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of new formed bone of the BMP-3-coated corundum-blasted or hydroxy-apatite-coated TiAl4V6 test devices compared to the non-coated controls of the same type (P < 0.01). Light microscopy demonstrated osseointegration without connective tissue membrane around the surface of the implants after 2, 5, and 8 weeks. Better osseointegration was achieved in the hydroxy-apatite-coated implants than in the corundum-blasted implants. CONCLUSIONS: Our results indicate that composite metal implants, as used in endoprosthetics and implantology, are suitable carriers for BMP-3 and improved fixation of the implants can be achieved.

Delivering health care benefits: staying focused on real solutions.

All signs point to an explosion of new approaches to financing, delivering, managing and purchasing health care. However, before employers abandon the current model, they need to verify that the alternatives will be truly advantageous and that new approaches will not place employees at greater risk than they are today. A through assessment of the advantages and risks of various approaches will equip employers to make the best business decisions and to be articulate participants in the coming debate.

Malignant transformation of a multiple cartilaginous exostosis--a case report.

A patient is reported who had multiple cartilaginous exostoses with malignant transformation of a pelvic osteochondroma.

Ectopic bone formation by composites of BMP and metal implants in rats.

Disc-shaped implants of titanium alloy (Ti-6Al-4V) were treated on one side by corundum-blasting (CB) or by coating with hydroxyapatite (HA) or pure titanium (Ti) using plasma spraying. Half of the implants were additionally coated with purified swine BMP-3. The composites and the uncoated controls were implanted into abdominal wall-muscle pouches of rats. 25 days after implantation, ectopic bone formation could be observed macroscopically and histologically in a high frequency in all 3 groups of BMP-coated implants, whereas the controls were constantly inactive. The volumes of induced bone were similar for BMP-3-coated pure Ti and HA implants, while CB implants were significantly less active. Our findings indicate that the bone formation process is influenced by the chemical composition and by the structure of the implant surface.

The Wagner revision stem in alloarthroplasty of the hip.

Forty-one Wagner revision stems were implanted at the Orthopedic Department of the University of Tübingen between July 1990 and January 1993. We report the results of 37 patients at an average follow-up of 27 months (13-48 months) postoperatively. The main indication was stem loosening with considerable loss of bone. In addition, we used the implant 4 times in primary arthroplasty. At follow-up examination 33 patients (89%) were satisfied with the postoperative outcome. According to the Merle D'Aubigné score (12-point scale), 32 patients showed a poor functional result of less than 6 points preoperatively. Postoperatively, the results of 36 patients could be classified as very good to good. To categorise the radiological destruction of the implant bed, we used the femoral shaft defect classification of the DGOT (Deutsche Gesellschaft für Orthopädie und Traumatologie) in conjunction with the classification of Pak and Paproski [5, 11]. Twenty patients presented with trochanteric and calcar defects, and 11 patients with a combination of a calcar and shaft defect. We found a circular shaft defect in 2 patients. In 7 cases we assessed the bone remodelling postoperatively as very good, with strong newly formed bone structures, and in 25 cases as good, with remodelling of the old stem bed and bony structuring of the osteolyses. A secondary sinking in of the Wagner stem was seen in 7 cases. Only one stem had to be revised because of pain symptoms and loosening; in all other cases a secondary stabilisation of the revision-stem took place. With the Wagner revision stem, there is the possibility of achieving mechanical stability even in situations with massive bone loss. The evacuation of bone cement and granulation tissues is facilitated by the transfemoral approach, bony remodelling is accelerated, and bone grafting is often not necessary. As our short-term results show, the concept is a promising one. Nevertheless, we will be very careful in following these patients in the long term, as we have noticed stem sinkage in a small percentage of cases.

Operative release of the impingement syndrome. Indication, technique, results.

We examined the long-term results of two different methods of shoulder decompression (Neer acromioplasty and resection of the coracoacromial ligament) after an average observation period of 8 years. Clinical and radiological features were evaluated in 48 patients with 50 treated shoulders, as was the subjective result of the treatment in 58 patients with 61 operated joints. Pain was substantially eased in 93% (acromioplasty) and 100% (ligamentary resection), mobility improved in 76% and 83%, respectively. A favourable result was achieved in 86% of the acromioplasty cases and in 75% of the ligament resection cases. In one-third of the shoulders, an increasing degeneration of joint structures could be demonstrated radiologically; the degree depended on the severity of the initial rotator cuff injury, not on the method of shoulder decompression. The differences between both surgical methods examined were not statistically significant, but acromioplasty provides a superior extension of the subacromial space and protection for the reconstructed rotator cuff tendons. Our results compare favourably with other published studies. The methods described are suitable for the treatment of subacromial impingement.

[Intraoperative assessment of leg length in alloplastic hip joint replacement]. / Die intraoperative Bestimmung der Beinlänge beim alloplastischen Hüftgelenkersatz.

A new measuring device has been developed at the Orthopedic Clinic of the University of Tübingen. Its task is to ensure that the right length of leg is selected intraoperatively. The method of measurement can be used in all approaches for alloplastic hip replacement when the patient is in the supine position. Measurement is quick, non-invasive, and can be carried out in a direct comparison to the contralateral leg, using measuring points at the iliac crest and the upper edge of the patella. In a prospective randomized study we were able to demonstrate on 53 patients that the use of this newly-developed measuring device improves the accuracy of the length of the operated leg as compared to the contralateral leg, so that the difference is only +/- 0.5 cm (post-operative difference in length of leg without use of the measuring device 1.1 cm on average, with the measuring device 0.5 cm; p < 0.05).

[Osseointegration of titanium test bodies of different surface properties in metaphyseal bone sites of the dog--a biomechanical and histological analysis]. / Das Einwachsverhalten von Titan-Prüfkörpern unterschiedlicher Oberflächenbeschaffenheit im metaphysären Knochenlager des Hundes--eine biomechanische und histologische Analyse.

The alternative to the anchoring of an endoprosthesis by means of cement is the biological fixation by an ingrowth of bone into the implant surface (osseointegration). We examined the implant fixation properties of titanium experimental devices with 3 different surface structures after press-fit implantation into the bony bed of 12 dogs. One third of the 48 implants had a micro-structured surface roughened by grit-blasting, one third a roughened surface with an additional macro-groove structure (combination surface), and the remaining third a porous hydroxyapatite (HA) coating. Twelve weeks after implantation the bony ingrowth was evaluated biomechanically by measuring the force required to pull out the implant from the surrounding bone and histologically by morphometric assessment of microradiographs. In the pull-out-experiment the shearing forces were significantly lower (p < 0.01) in the devices with a roughened surface in comparison to the devices with a micro- and macro-structured surface and the HA surface. Thus, there was no significant difference between the forces required to pull out the devices with the porous HA surface and those with the combination surface. The histomorphometric assessment of bone density in the immediate vicinity of the implant and the extent of the direct contact surface of the bone implant resulted in no significant difference in all 3 groups. We did not find an interposing layer of fibrous tissue at the interface. We can demonstrate that roughening of the surface in combination with a groove structure creates a better bond between implant and bone than a roughening alone.(ABSTRACT TRUNCATED AT 250 WORDS)

[Double-contrast arthro-CT in diagnosis of shoulder instability]. / Doppelkontrast-Arthro-CT zur Diagnostik von Schulterinstabilitäten.

Timeless and lesion-related treatment are important in the different shoulder instabilities in order to get a good functional result. Within the step-by-step programme of diagnostic possibilities the double contrast computerised arthrotomography is particularly indicated in recurrent posttraumatic and habitual dislocations, in subluxations as well as for clarification of causes of postoperative recurrence. Besides the documentation of skeletal changes (Hill-Sachs-lesion, Bankart defect), double-contrast arthro-CT offers the possibility to identify detachments of the joint capsule or labral tears. Between 11/90 and 9/93 we performed 38 double contrast arthro-CTs for recurrent shoulder instabilities. 35 men and 3 women were examined. The mean age of the sportive patients were 29 years. Preoperatively we diagnosed in 21 cases a recurrent posttraumatic, in 7 cases a habitual shoulder instability. Apart from one multidirectional and three posterior instabilities we found two cases of subluxation. In the meantime 24 patients were treated with an open stabilising operation of the shoulder. The operative findings were compared with the results of double contrast arthro-CT. In a total of 38 performed arthro-CTs we found labral tears in 4 cases, 14 labral dissections, and 10 times a complete labral discontinuity. 8 of 9 labrum dissections found intraoperatively were correctly identified on CT. One dissection was not even seen retrospectively on arthro-CT. Six of nine complete labrum discontinuities were seen on arthro-CT, three described as a dissection. All capsular detachments and bony Bankart lesions found on CT were confirmed intraoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)