[Penile paraffinoma-Treatment strategies]. / Penile Paraffinome ­ therapeutische Strategien.

BACKGROUND: Penile paraffinomas are a consequence of an injection of mineral oils for augmentation. As an result of the foreign body reaction local complications regularly occur, which require a plastic reconstructive intervention. So far 8 cases have been treated in our clinic over the last 20 years. OBJECTIVE: Presentation of the operative treatment techniques for penile paraffinoma as well as the indications and complications. MATERIAL AND METHODS: After reviewing the relevant literature, we analyzed the data of our own patient cohort. Since 1999 a total of 8 patients with lipogranuloma underwent surgical treatment at the St. Antonius Hospital in Eschweiler. RESULTS: The choice of a plastic reconstructive treatment depends on the extent of the paraffinoma. If it is limited to the foreskin, a radical circumcision is sufficient but if it extends to the skin of the penile shaft, a plastic defect coverage with a mesh graft, a full skin graft or a scrotal skin flap is required. In cases with additional pathologies, such as urethral fistulas, auxiliary reconstructive procedures should be performed. CONCLUSION: For optimal cosmetic and functional results, the surgeon must master a broad spectrum of plastic reconstructive techniques. In selected complex cases an interdisciplinary approach consisting of urologists and plastic surgeons can be necessary.

Vacuum-compatible photon-counting hybrid pixel detector for wide-angle x-ray scattering, x-ray diffraction, and x-ray reflectometry in the tender x-ray range.

A vacuum-compatible photon-counting hybrid pixel detector has been installed in the ultra-high vacuum reflectometer of the four-crystal monochromator beamline of the Physikalisch-Technische Bundesanstalt at the electron storage ring BESSY II in Berlin, Germany. The setup is based on the PILATUS3 100K module. The detector can be used in the entire photon energy range accessible at the beamline from 1.75 keV to 10 keV. Complementing the already installed vacuum-compatible PILATUS 1M detector used for small-angle x-ray scattering (SAXS) and grazing incidence SAXS, it is possible to access larger scattering angles. The water-cooled module is located on the goniometer arm and can be positioned from -90° to 90° with respect to the incoming beam at a distance of about 200 mm from the sample. To perform absolute scattering experiments, the linearity, homogeneity, and angular dependence of the quantum efficiency, including their relative uncertainties, have been investigated. In addition, the first results of the performance in wide-angle x-ray scattering, x-ray diffraction, and x-ray reflectometry are presented.

Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. METHODS: 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. RESULTS: Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. CONCLUSIONS: We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

The impact of depressive symptoms on health-related quality of life in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Health-related quality of life (HRQOL) is an important issue in the context of dementia care. The purpose of this study was to investigate the association between HRQOL and depressive symptoms in patients with subjective cognitive decline (SCD) and subtypes of mild cognitive impairment (MCI) and Alzheimer´s disease (AD). METHODS: In this cross-sectional, observational study, a control group and four experimental groups (SCD, non-amnestic MCI, amnesticMCI, AD) were compared. Neuropsychological measurers (NTBV) and psychological questionnaires were used for data collection. RESULTS: The control group scored higher than patients with SCD, naMCI, aMCI, or AD for the Mental Health Component Score (MHCS) of the Short Form of the Health Survey (SF-36). The Physical Health Component Score (PHCS) of the SF-36 differed only between some groups. Furthermore, cognitive variables were more strongly associated with the physical aspects of HRQOL, whereas depressive symptoms were more strongly related with the mental aspects of HRQOL. CONCLUSIONS: HRQOL and depressive symptoms are closely related in patients with cognitive impairments. Therefore, it is of great importance to assess patients with subjective impairment carefully in terms of depressive symptoms.

Facial emotion recognition and its relationship to cognition and depressive symptoms in patients with Parkinson's disease.

BACKGROUND: Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST). RESULTS: Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER. CONCLUSIONS: The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.

The electronic structure of perfluorodecalin studied by soft X-ray spectroscopy and electronic structure calculations.

Fluorine and carbon K absorption and emission spectra of liquid perfluorodecalin are presented and analyzed in terms of density functional calculations-configuration interaction. A comprehensive view of the electronic structure is given, and site-specific intramolecular interactions are investigated in detail. It is found that, while the outer fluorine atoms have excess charge in the ground state, the lowest excitations must be associated with charge transfer towards the inner carbon atoms.

Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers.

The pharmacokinetics and pharmacodynamics of a highly concentrated cyclodextrin-based intranasal (i.n.) midazolam formulation containing the absorption-enhancer chitosan were studied in 12 healthy volunteers and compared with intravenous (i.v.) midazolam. The pharmacodynamic (PD) effects were assessed using quantitative electroencephalography (EEG). Maximal plasma concentrations of 63 and 110 ng/ml were reached at 8.4 and 7.6 min after 3 and 6 mg i.n. midazolam, respectively. After 5 mg i.v. and 6 and 3 mg i.n. midazolam, the times to onset of significant EEG effects in the ß2 band (18-25 Hz) were 1.2, 5.5, and 6.9 min, respectively, and the times to loss of response to auditory stimuli were 3.0, 8.0, and 15.0 min, respectively. A sigmoid maximum-effect (E(max)) model indicated disequilibrium between plasma and effect-site concentrations, with equilibration half-lives of 2.1-4.8 min. The observed pharmacokinetic-PD (PK-PD) properties suggest that i.n. midazolam deserves to be evaluated as an easy and noninvasive method of administering a first benzodiazepine dose, e.g., in out-of-hospital emergency settings with no immediate i.v. access.

Early infant diet in children at high risk for type 1 diabetes.

Infant diet affects health and development. The aim of our study was to investigate WHO infant feeding compliance in children who have a first degree family history of type 1 diabetes (T1D). One hundred and fifty children who were first degree relatives of patients with T1D were intensively followed from birth in the BABYDIET intervention study. Infant feeding, infections, and medication were recorded daily by participating families. Weight and length of children were obtained from paediatric records. Only 5% of the families followed the WHO recommendations for infant feeding that include full breastfeeding for at least 6 months (18.8% of children) and introduction of complementary foods under continued breastfeeding thereafter (22.2% of children). Maternal age in the first quartile (<29 years; p<0.0001), and maternal smoking (p<0.0001) were associated with an earlier introduction of solid food and reduced breastfeeding. Full breastfeeding > or =6 months was associated with reduced frequency of gastrointestinal infections (12 vs. 38%, p=0.02) and antibiotic treatment (24 vs. 48%, p=0.04). Our findings indicate that WHO infant feeding recommendations were poorly followed by families with a family history of T1D. Action to improve levels of infant feeding behaviour is essential, especially among young mothers with T1D.

Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk.

AIMS/HYPOTHESIS: Our aim was to determine the relationships between autoantibodies to zinc transporter 8 (ZnT8), genotypes of the ZnT8-encoding gene SLC30A8 and type 1 diabetes risk. METHODS: ZnT8 autoantibodies (ZnT8A) were measured in sera of 1,633 children with a first-degree family history of type 1 diabetes and who were prospectively followed from birth. Antibodies were measured by Protein A-based radiobinding assays and COOH-terminal (R325, W325 or Q325 variants) or NH(2)-terminal constructs of human ZnT8. SLC30A8 genotyping at single-nucleotide polymorphism (SNP) rs13266634 was performed on 1,170 children. RESULTS: Antibodies against COOH-terminal ZnT8 constructs (ZnT8A-COOH) developed in 58 children as early as 9 months of age (median 3 years). They were detected in 55 of 128 (43%) children with autoantibodies to insulin, GAD and/or insulinoma-associated protein 2 and 34 of 42 (81%) who progressed to diabetes. The additional presence of ZnT8A-COOH stratified diabetes risk in islet autoantibody-positive children (p < 0.0001). SLC30A8 genotype strongly influenced ZnT8A type and diabetes risk in ZnT8A-COOH-positive children. Antibody binding against the ZnT8 R325 variant was strictly correlated with the number of the corresponding SLC30A8 R325-encoding alleles, whereas binding against the W325 variant was highest in children who had SLC30A8 W325-encoding alleles (p = 0.001). Moreover, ZnT8A-COOH-positive children who carried homozygous SLC30A8 SNP rs13266634 genotypes progressed faster to diabetes than those who were heterozygous (59% [95% CI 42.3-75.7%] vs 22% [95% CI 0-44.3%] within 5 years; p = 0.01). CONCLUSIONS/INTERPRETATION: Autoimmunity against the COOH-terminal region of ZnT8 is a highly relevant prognostic feature in childhood type 1 diabetes. Risk stratification in ZnT8A-COOH-positive children is further improved by SLC30A8 genotyping.

[Effect of breastfeeding on the risk of becoming overweight in offspring of mothers with type 1 diabetes]. / Einfluss des Stillens auf das Risiko für Ubergewicht bei Kindern von Müttern mit Typ-1-Diabetes.

BACKGROUND AND OBJECTIVE: Breastfeeding is considered to be a protective factor against obesity in healthy children. But previous studies about the effect of breastfeeding in the offspring of diabetic mothers have provided inconsistent results. It was the aim of this study to assess the effect of breastfeeding on the risk of becoming overweight at two years of age in children of these mothers. METHODS: In a prospective cohort study data on exclusive or partial breastfeeding habits, were obtained from questionnaires given to 816 mothers, aged between 17 and 43 years, with type 1 diabetes. Weight and height of their children was obtained from their pediatric records. Children with a BMI > or = 90th percentile were classified as being overweight. RESULTS: 77.9 % of all mothers started breastfeeding after the child's birth. Six months later 33.1 % were still breast-feeding. 14.5 % of all children were overweight at two years of age. After adjusting for smoking in pregnancy and the child's gender and birth weight, there was a risk reduction for overweight of 60 % (OR=0.405; 95%-CI: 0.211-0.779) for breastfeeding duration of 12 to 25 weeks. A similar positive association was found for predominant breastfeeding for a duration of at least four months (OR=0.500; 95%-CI: 0.282-0.887). Protective effects were already present when the duration of breastfeeding was four weeks or more. CONCLUSIONS: Mothers with type 1 diabetes breastfed less and for a shorter duration than those in the general population. Breastfeeding duration of at least four weeks was associated with a reduced risk for overweight at two years of age. Special needs regarding diabetes management have to be taken into account.

Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA(1c).

AIMS/HYPOTHESIS: The risk of type 1 diabetes is reduced in the children of mothers with type 1 diabetes compared with children of fathers with type 1 diabetes. We asked whether children of mothers with type 1 diabetes also have a decreased risk of developing islet autoantibodies, and which factors associated with maternal diabetes contribute to a reduced islet autoantibody risk in offspring. METHODS: Singleton offspring of a mother (n = 1,008) or father with type 1 diabetes (n = 578) from the BABYDIAB study were included. Children were followed from birth for the development of islet autoantibodies defined as two or more autoantibodies to insulin, glutamic acid decarboxylase or insulinoma antigen 2 in two or more blood samples. RESULTS: Islet autoantibody risk was lower in children of mothers with type 1 diabetes (5 year risk, 3.2% vs 5.7% in children of fathers with type 1 diabetes; p = 0.04). Among factors that differed between pregnancies from mothers with and without type 1 diabetes, birthweight was associated with islet autoantibody risk. Risk was reduced in children with birthweights in the lower (adjusted HR 0.33; 95% CI 0.14-0.75; p = 0.009) and upper (HR 0.45; 95% CI 0.21-0.97; p = 0.04) tertiles compared with the middle tertile. A sub-analysis of maternal HbA(1c) suggested that moderately elevated third trimester maternal HbA(1c) was also associated with a reduced islet autoantibody risk in children of mothers with type 1 diabetes (5.7-7%; HR 0.38; 95% CI 0.15-0.96; p = 0.04 vs children of mothers with HbA(1c) < 5.7%). CONCLUSIONS/INTERPRETATION: The risk of islet autoimmunity is modified by maternally influenced events such as birthweight.

The Basel early-detection-of-psychosis (FEPSY)-study--design and preliminary results.

UNLABELLED: Early detection and therapy of schizophrenic psychoses have become broadly accepted aims in psychiatry, recently even in very early stages of the disorder when clear diagnostic criteria are not yet fulfilled. However, reliable and widely applicable methods do not yet exist. This study aims at contributing to the improvement of the early assessment of psychosis. METHOD: Individuals potentially at risk are identified by a newly developed stepwise screening procedure. Identified subjects are then examined extensively and followed-up for at least 5 years to detect actual transition to psychosis. RESULTS: Of 50 subjects who have been followed up for 1-5 years by now, 16 have progressed to frank psychosis, 12 of them during the first 12 months of follow-up. CONCLUSION: At this stage, our approach seems to be promising for the early detection of psychosis. Further results from this ongoing study will hopefully permit us to optimize the assessment procedure.

Early detection and treatment of schizophrenia: how early?

OBJECTIVE: Whereas early detection and therapy of schizophrenic psychoses until some time ago concentrated on frank schizophrenia, during the last years some centres have also started to treat patients even before a clear diagnosis could be established. This paper attempts to discuss if and when this is justified in the light of recent research. METHOD: Mini review of literature. RESULTS: The rationale for early detection and treatment of schizophrenia is based on several observations: diagnosis and treatment of schizophrenia are often seriously delayed. Consequences of the disease are severe already in the early undiagnosed phase of the disorder and early treatment seems to improve the course of the disease. It can therefore be stated quite safely that patients should be treated as early as possible. However, the question of how early has not been sufficiently answered up to now. CONCLUSION: We are at the moment in an ethical dilemma between either diagnosing and treating this disorder too late or too early. The only way and prerequisite for solving this dilemma is a more reliable identification of individuals at risk and the beginning disease process.

Radiological findings in individuals at high risk of psychosis.

OBJECTIVE: To assess the prevalence of radiological magnetic resonance imaging (MRI) findings in individuals at high risk of schizophrenia. METHODS: MRI scans from individuals at high risk of schizophrenia (HR; n = 37) were assessed by a radiologist blind to group status and compared with scans from patients with first episode psychosis (FE; n = 30), depressive controls (DC; n = 17), and healthy controls (HC; n = 26). RESULTS: There was a significantly higher proportion of radiological findings in individuals at high risk of schizophrenia (35%) and patients with first-episode psychosis (40%) than in patients with depression (18%) or healthy controls (12%). These differences were specific to findings regarded as potentially clinically significant as opposed to normal variants; however, there was no indication for medical treatment. CONCLUSIONS: The results suggest that a large proportion of those at high risk of psychosis have radiological findings on MRI scanning, and that the prevalence of radiological findings in this group is similar to that in patients with first episode psychosis.

Validation of a newly developed mini-knemometer for premature infants.

A newly developed knemometric device for lower leg length measurement in premature and newborn infants is presented and validated. The present study was performed to establish a standardized method of use of this instrument. Two independent observers obtained 10 subsequential readings per measurement in three infants over 43 days, after which analysis showed that 5 subsequential readings per measurement gave comparable technical errors. Thirty-one premature infants were assessed by knemometry by two independent observers. The correlation coefficient of all measurements was 0.998. The acquired technical error (mean Standard Deviation (SD) of 5 sequential readings) over a total observation period of 294 days in all studied infants was 0.06 and 0.05 mm, respectively. By a mean lower leg length growth velocity of 0.52 mm per day the technical error amounted to 11% of daily bone growth. The described mini-knemometer is an accurate device for the detection of daily individual growth. A learning period of 21 days is necessary to obtain reliable results.

Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans.

The objective of the present study was to evaluate the effects of EMD 61753 (asimadoline), a kappa-opioid receptor agonist with restricted access to the central nervous system, on postoperative pain in patients who underwent knee surgery and on nociceptive thresholds and inflammation in rats treated with Freund's complete adjuvant. Patients treated with EMD 61753 (10 mg p.o.) tended to report an increase in pain, as evaluated by a visual analog scale and by the time to the first request for and the total amount of supplemental analgesic medication. The global tolerability of EMD 61753 was assessed as significantly inferior to that of a placebo by the investigator. In rats, the bilateral intraplantar (i.pl.) injection of EMD 61753 (0.1-3.2 mg) resulted in dose-dependent antinociception in both inflamed and noninflamed paws, with a peak at 5 min after injection, as evaluated by the paw pressure method. However, at later time points (1 h-4 days), a significant decrease in the paw pressure threshold was observed, confirming its tendency toward a hyperalgesic action in humans. This was accompanied by an increase in paw volume and paw temperature, with a peak at 6 h after injection. EMD 61753 (1.6 mg)-induced analgesia was blocked by the peripheral opioid receptor antagonist naloxone methiodide (2.5-10 mg/kg s.c.) and by the kappa receptor antagonist nor-binaltorphimine (0.1 mg; i.pl.). In contrast, EMD 61753 (1.6 mg)-induced hyperalgesia and increases in paw volume and paw temperature were blocked neither by naloxone methiodide (10-40 mg/kg s.c.) nor by dizocilpine maleate (0.003-0.009 mg i.pl.), a N-methyl-D-aspartic acid receptor antagonist. These data show differentially mediated peripheral actions of EMD 61753: kappa-opioid receptor-induced analgesia and nonopioid, non-N-methyl-D-aspartic acid hyperalgesic and proinflammatory effects.

[Distal femoro-popliteal bypass using Esmarch tourniquet ischemia]. / Der distale femoro-popliteale Bypass unter Verwendung der Esmarchschen Blutleere.

The Esmarch bandage is an effective substitute for vascular clamps in distal femoro-popliteal or tibial bypass surgery. Intimal trauma caused by clamping is avoided, vasa vasorum are preserved due to only semicircumferential dissection of vessels. This method is particularly suitable for heavy calcified rigid vessel walls. We demonstrate this technique, which was employed in 8 patients (10 bypasses). The use of this technique requires neither a longer operation- nor clamping time. The postoperative course of all but one patients develops normally and the technique does not provoke any pathological results in the area of operation. Advantages of the procedure compared to conventional techniques will be discussed.

Influence of nutrition on growth in premature infants: assessment by knemometry.

Lower leg length measurements in 19 healthy preterm infants were obtained by knemometry to assess short term growth. Eight infants received fortified human milk and 11 infants commercially available preterm formulas. Two independent observers measured lower leg length in each infant daily during the study period, weight was measured daily with a neonatal scale. While weight gain showed linearity in all infants, lower leg length growth showed mini growth spurts of 5 +/- 1.7 days, growth periods of 20 +/- 11 days or both types of short term growth. The overall weight gain was 35 +/- 5.6 g/day in infants fed human milk and 33 +/- 7 g/day in infants fed preterm formula. The overall lower leg length growth velocity was 0.51 +/- 0.04 mm/day versus 0.54 +/- 0.09 mm/day, respectively. Both groups had comparable weight and length increments. No correlation existed between the type of nonlinear lower leg length growth (mini growth spurts versus growth periods) and the feedings received by the infants.

No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.

Pain treatment with centrally acting opiates is limited by tolerance. Tolerance is a decreasing effect of a drug with prolonged administration of that drug or of a related (e.g., endogenous) compound acting at the same receptor. This is often associated with a downregulation of receptors. In peripheral inflamed tissue, both locally expressed opioid peptides and morphine can produce powerful analgesia mediated by similar populations of opioid receptors. We hypothesized that the chronic presence of endogenous opioids in inflamed joints might convey downregulation of peripheral opioid receptors and tolerance to the analgesic effects of intraarticular morphine. We assessed these effects after arthroscopic surgery in patients with and without histologically verified synovial cellular infiltration, and we examined synovial opioid peptides and opioid receptors by immunocytochemistry and autoradiography, respectively. We found that, despite an abundance of opioid-containing cells in pronounced synovitis, morphine is at least as effective as in patients without such cellular infiltrations, and there is no major downregulation of peripheral opioid receptors. Thus, opioids expressed in inflamed tissue do not produce tolerance to peripheral morphine analgesia. Tolerance may be less pronounced for peripherally than for centrally acting opioids, which provides a promising perspective for the treatment of chronic pain in arthritis and other inflammatory conditions.