Biomedical subjects
Publications and source records attributed to M Binder.
Chicken CITED3 (cCITED3) is a novel gene, which is expressed in the pre-somitic mesoderm, the mesonephric tubules, the Wolffian ducts and collecting tubules of the developing urogenital system and in the cranial sensory ganglia. Sequence analysis revealed that cCITED3 encodes a protein which contains two conserved domains that have been described for members of the CITED family.
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BACKGROUND: Digital epiluminescence microscopy (DELM) has been reported to be a useful technique for the follow-up of melanocytic nevi. One of the promises of this technique is to identify modifications over time that indicate impending or incipient malignancy and to facilitate surveillance of melanocytic skin lesions, particularly in patients with multiple clinically atypical nevi. OBJECTIVE: Our purpose was to report on patterns of modifications over time observed in benign melanocytic skin lesions and melanoma. METHODS: A total of 1862 sequentially recorded DELM images of melanocytic lesions from 202 patients (mean age, 36.1 years; 54.0% female patients) with multiple clinically atypical nevi were included in the analysis. The median follow-up interval was 12. 6 months. Melanocytic lesions with substantial modifications over time (enlargement, changes in shape, regression, color changes or appearance of ELM structures known to be associated with melanoma) were excised and referred to histopathologic examination. RESULTS: A total of 75 melanocytic skin lesions (4.0%) from 52 patients (mean age, 33.3 years; 63.5% female patients) showed substantial modifications over time and were excised and referred to histopathologic examination. Eight changing lesions were histologically diagnosed as early melanomas. These lesions frequently showed focal enlargement associated with a change in shape as well as appearance of ELM structures that are known to be associated with melanoma. In contrast, the majority of benign changing lesions (common and atypical nevi) showed symmetric enlargement without substantial structural ELM changes. Six of the 8 patients in whom melanoma developed were unaware of the fact that the lesion had changed over time. CONCLUSION: We demonstrate that follow-up of melanocytic lesions with DELM helps to identify patterns of morphologic modifications typical for early melanoma. DELM may therefore serve as a useful tool to improve the surveillance of patients with multiple atypical nevi.
OBJECTIVES: Recent data indicate an increased vascular reactivity due to an overactivity of the sympathetic nervous system in women with pre-eclampsia. We therefore evaluated whether this increased vascular reactivity can be detected prior to the clinical manifestation of preeclampsia by the use of a physiological stimulus. DESIGN: Prospective data collection. SETTING: Clinic of Obstetrics and Gynecology in a 2000 bed tertiary care hospital. PARTICIPANTS: One hundred and twenty-three pregnant women between the 16th to 20th week of gestation. INTERVENTIONS: A cold pressor test was performed by positioning an ice-bag on the forehead of the woman for 3 min. Blood pressure and heart rate were monitored by a continuous, noninvasive blood pressure measurement device during the stimulus and after removal of the icebag. A clinical follow-up was carried out by review of the charts after delivery to identify those women who have developed pre-eclampsia. RESULTS: Ten (8%) out of 123 pregnant women developed pre-eclampsia. During the cold pressor test systolic as well as diastolic blood pressure increased significantly and was more pronounced in women developing pre-eclampsia compared with healthy pregnant women (systolic blood pressure: 14.2 +/- 5.5 versus 8.5 +/- 7.2 mmHg, P= 0.02; diastolic blood pressure: 7.3 +/- 4.9 versus 3.9 +/- 4.7 mmHg, P=0.03). The change in heart rate was similar between both groups (8 +/- 2.6 versus 10.4 +/- 6.4 beats/min, not significant). CONCLUSIONS: An increased vasoconstrictive response to a physiological stimulus is present in women with pre-eclampsia as a sign of an increased vascular reactivity prior to clinical manifestation of the disease. The cold pressor test may be a suitable diagnostic tool to identify women, who will develop pre-eclampsia. However, future studies in larger cohorts are required to establish the final value of this test.
Early melanoma is often difficult to differentiate from benign pigmented skin lesions (PSLs). Digital epiluminescence microscopy (DELM) and automated image analysis could represent possible aids for inexperienced clinicians. We designed an automated computerized image analysis system that has the potential for use as an additional tool for the differentiation of melanoma from dysplastic naevi and common naevi. The PC-based pilot system was attached to a common DELM system as the image source. Digital images of PSLs were automatically segmented and a panel of 107 morphological parameters were measured. Additionally, seven clinical parameters were evaluated and used as an additional source of information. Neural networks were then trained to distinguish melanoma from benign PSLs. One class of networks was trained solely based on the morphometric features, whereas the second class of networks was trained on the combination of morphometric and clinical features. The automatic segmentation algorithm was correct in 96% of cases. Using three-way receiver operating characteristic (ROC) analysis, for networks trained solely on morphometric features the volume under surface (VUS) was 0.617 (SD 0.036). The performance was significantly better for networks trained on the combination of both morphometric and clinical features (VUS = 0.682, SD 0.035). In a dichotomous model, distinguishing benign lesion (common naevi + dysplastic naevi) from melanoma, the area under the curve (AUC) from two-way ROC analysis was 0.942 (SD 0.018) for networks trained solely on morphometric features and 0.968 (SD 0.012) for those trained on the combination of clinical and morphometric data (P= NS). Automated feature extraction from PSLs and the training of neural networks as classifiers has thus shown satisfactory performance in a large scale experiment. The addition of clinical data significantly increases the diagnostic performance for distinguishing three classes of lesions (i.e. common naevi, dysplastic naevi and melanoma). Such integrated systems hold promise as a decision aid for the diagnosis of PSLs.
BACKGROUND: Dermatologists need to interpret an increasing number of research studies and diagnostic tests. Understanding the techniques for interpreting test results and making decisions based upon those tests represent important tools for decision making for both clinicians and researchers. OBJECTIVE: This article focuses briefly on the key parameters of diagnostic tests: sensitivity, specificity, prevalence, predictive values, likelihood ratios, and the concept of receiver-operating-characteristic (ROC) curves. A simple example is presented in a step-by-step manner. CONCLUSION: The principles of interpreting test results are easy to learn and applicable in daily clinical routine. Therefore, dermatologists should be familiar with the concepts outlined in this paper.
Human 2,4-dienoyl-CoA reductase (2,4-reductase; DECR) and rat monofunctional Delta(3)-Delta(2)-enoyl-CoA isomerase (rat 3, 2-isomerase; ECI) are thought to be mitochondrial auxiliary enzymes involved in the beta-oxidation of unsaturated fatty acids. However, their function during this process has not been demonstrated. Although they lack obvious peroxisomal targeting signals (PTSs), both proteins have been suggested previously to also occur in the mammalian peroxisomal compartment. The putative function and peroxisomal location of the two mammalian proteins can be examined in yeast, since beta-oxidation of unsaturated fatty acids is a compartmentalized process in Saccharomyces cerevisiae requiring peroxisomal 2,4-dienoyl-CoA reductase (Sps19p) and peroxisomal 3, 2-isomerase (Eci1p). A yeast sps19Delta mutant expressing human 2, 4-reductase ending with the native C-terminus could not grow on petroselinic acid [cis-C(18:1(6))] medium but could grow when the protein was extended with a PTS tripeptide, SKL (Ser-Lys-Leu). We therefore reason that the human protein is a physiological 2, 4-reductase but that it is probably not peroxisomal. Rat 3, 2-isomerase expressed in a yeast eci1Delta strain was able to re-establish growth on oleic acid [cis-C(18:1(9))] medium irrespective of an SKL extension. Since we had shown that Delta(2,4) double bonds could not be metabolized extra-peroxisomally to restore growth of the sps19Delta strain, we postulate that rat 3,2-isomerase acted on the Delta(3) unsaturated metabolite of oleic acid by replacing the mutant's missing activity from within the peroxisomes. Immunoblotting of fractionated yeast cells expressing rat 3, 2-isomerase in combination with electron microscopy supported our proposal that the protein functioned in peroxisomes. The results presented here shed new light on the function and location of human mitochondrial 2,4-reductase and rat monofunctional 3,2-isomerase.
PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.
Insufficient conserved home-made products are the main cause of botulism in Denmark. We present a case of botulism caused by a commercially produced vegetable pie conserved by traditional bottling without addition of preservatives. Clostridium botulinum was grown from faeces of the index case indicating an intestinal infection. An action plan set up by the medical and veterinarian authorities functioned well and further spread of the disease was avoided. More cases of botulism may be seen in the future, if procedures ensuring proper conservation in food production are not adhered to.
Consistent chromosomal rearrangements are found in a large number of hematopoietic tumors. In many cases, these rearrangements disrupt genes whose normal function is required for the proper development of blood cells. Excellent examples are the chromosomal rearrangements t(8;21)(q22;q22), t(12;21)(p13;q22), and inv(16)(p13q22) that disrupt two of the genes encoding a small family of heterodimeric transcription factors, core-binding factors (CBFs). CBFs consist of a DNA-binding CBFalpha subunit and a non-DNA-binding CBFbeta subunit. The t(8;21), associated with de novo acute myeloid leukemias, disrupts the CBFA2 (AML1) gene, which encodes a DNA-binding CBFalpha subunit. The t(12;21), the most common translocation in pediatric acute lymphocytic leukemias, also disrupts CBFA2. The CBFB gene, which encodes the non-DNA-binding subunit of the CBFs, is disrupted by the inv(16) in de novo acute myeloid leukemias. All chromosomal rearrangements involving the CBFA2 and CBFB genes create chimeric proteins, two of which have been unequivocally demonstrated to function as transdominant negative inhibitors of CBF function. Both the Cbfa2 and Cbfb genes are essential for normal hematopoiesis in mice, because homozygous disruption of either gene blocks definitive hematopoiesis. Recent data suggest that Cbfa2 and Cbfb are required for the emergence of definitive hematopoietic stem cells in the embryo from a putative definitive hemangioblast precursor. The transdominant negative inhibitor of CBF created by the inv(16), when present from the beginning of embryogenesis, also blocks the emergence of definitive hematopoietic cells in the embryo. On the other hand, chromosomal translocations involving the CBFA2 and CBFB genes in leukemias block hematopoiesis at later steps. This may reflect a difference in the timing at which translocations are acquired in the leukemias, which presumably is subsequent to emergence of the definitive hematopoietic stem cell. The cumulative data suggest that although the earliest requirement for Cbfa2 and Cbfb is for emergence of definitive hematopoietic stem cells, both genes are also required at later stages in the differentiation of some hematopoietic lineages.
In order to produce sophorolipids from whey, thereby lowering the lactose content and biological oxygen demand, a two-step batch cultivation process was developed including medium sterilization by filtration. In the first step, whey was sterilized by a combination of crossflow and sterile filtration. Because the sophorolipid-producing yeast Candida bombicola ATCC 22214 was not able to use lactose as a carbon source directly, the oleaginous yeast Cryptococcus curvatus ATCC 20509 was grown on deproteinized whey concentrates (DWC). With 1:1 diluted DWC-20, lactose was consumed as the carbon source and biomass (24 g/l dry weight content) as well as single-cell oil (SCO, 10 g/l) were produced. The cultivation broth was disrupted with a glass bead mill and it served as medium for growth (29 g cell dry mass/l) and sophorolipid production (12 g/l) of the yeast C. bombicola.
A 32-year-old man presented with a chronic rosacea-like dermatitis of the facial skin and the eyelids. The skin disorder had been present for 4 years and was unresponsive to multiple previous treatment attempts. Skin scrapings and a histologic examination of a biopsy specimen from the affected area revealed the presence of numerous Demodex mites. The patient was treated with oral ivermectin and subsequent topical permethrin resulting in complete and rapid clearing of the folliculitis. We believe that this case supports the view that Demodex mites may be pathogenic when they are present in large numbers. Oral treatment with 200 microg/kg ivermectin with subsequent weekly topical permethrin showed impressive treatment efficacy in a case refractory to conventional treatment.
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BACKGROUND: Epiluminescence microscopy (ELM) provides for increased accuracy in the clinical diagnosis of pigmented skin lesions (PSL). It is based on pattern analysis of ELM criteria, which requires experience. The recently introduced application of the ABCD score to ELM facilitates this by permitting lesion evaluation on the basis of predefined clinical criteria. OBJECTIVE: The present study was performed to evaluate the diagnostic performance of the ABCD rule for ELM in pigmented skin lesions testing dermatologists with varying skills from novice to expert. METHODS: Two hundred fifty electronic images of randomly selected, histologically proven PSL including 41 early melanomas (16.4%) were presented to the raters, and each image was scored according to the rules of the ABCD score and rated without the guidance of a scoring system on a scale from 1 = definitely benign to 5 = definitely melanoma. RESULTS: Our data show that the application of the ABCD rule significantly enhances diagnostic ability in less experienced dermatologists compared with rating without the guidance of a scoring system. In contrast, the diagnostic accuracy of dermatologists who are moderately to greatly experienced is not improved by use of the ABCD rule. CONCLUSION: Our experiments indicate that the application of the ABCD rule to ELM introduced by Stolz et al represents a useful enhancement for diagnosis of pigmented skin lesions in less experienced users. However, the method does fail to detect melanomas with 100% accuracy. Therefore further effort has to be made to make the diagnosis of melanoma easier and more accurate.
BACKGROUND: Epiluminescence microscopy (ELM) significantly increases the early diagnosis of pigmented skin lesions (PSL) using established criteria and pattern analysis. The ABCD rule for dermatoscopy (ie, ELM) provides a simplified approach to the interpretation of ELM images on the basis of asymmetry (A), border (B), color (C), and dermatoscopic structure (D). OBJECTIVE: We set out to determine whether the diagnostic accuracy of the ABCD scoring algorithm can be significantly improved by incorporating information about morphologic changes of the lesion observed and provided by the patient. METHODS: We prospectively collected 356 small pigmented skin lesions (< 1 cm) including 73 (20.5%) melanomas. Before excision all patients were asked whether the lesion had changed in size, color, or shape within the last year or whether they experienced any sign of ulceration or spontaneous bleeding. ELM images of the lesions were evaluated according to the ABCD rule for dermatoscopy to yield a semiquantitative score. Accuracy of diagnosis was evaluated in terms of sensitivity, specificity, and area under receiver operating characteristic curves (AUC). RESULTS: The frequency of reported changes was significantly higher for melanomas than benign PSL (65.8% vs 29.7%, P < .001). In a multivariate model morphologic change was a significant independent predictor of malignancy (odds ratio = 3.17, 95% confidence interval [CI]: 1.96 to 5.14, P < .001). The mean final score achieved when using the enhanced ABCD-E criteria including morphologic change (E) was significantly higher for melanomas (5.7, 95% CI: 5.3 to 6.0) than benign PSL (2.9, 95% CI: 2.8 to 3.1, P < .001). Diagnostic accuracy was significantly higher when the lesions were evaluated by the enhanced ABCD-E criteria as compared with the standard ABCD score (AUC(ABCD) = 0.87 vs AUC(ABCD-E) = 0.90; P = .006). CONCLUSION: Information about morphologic changes of PSL as reported by the patient is a useful extension of the ABCD rule for dermatoscopy.
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AIM: This study was conducted in order to evaluate the attention capacity during the school day and week, taking school life and others factors into account in 10,000 children (8 to 11 years old) in public Parisian schools. MATERIAL AND METHODS: The test used to measure attention was a paper and pencil test validated from the Zazzo test. The children answered a questionnaire before each test to obtain information concerning the time and day of the test, and concerning also the different life styles of children, particularly quantity and quality of sleep and composition of breakfast. The evaluation was performed four times in the morning and four times in the afternoon every day, to measure exactly the fluctuations of attention. This study lasted four weeks. The last evaluation week took place after the summer time change. RESULTS: The results showed the existence of an ultradian fluctuation of attention during the day, with the lowest level between 08.00 a.m. and 09.30 a.m. and the highest level between 04.00 p.m. and 04.30 p.m. The attention levels on Monday and Thursday, after a day without school, were not lowered. Furthermore, after a 2 days weekend the attention level was higher than after a 1 day and half weekend. The summer time change also worsened the attention capacity of children all along the next week. Finally, there was a statistical relationship between children attention capacity and their sleep practice. CONCLUSION: These results confirm the ultradian fluctuation of attention capacity and show the importance of the regularity in the child's life style with respect to their mental functioning.
In a prospective, randomised trial, 75 patients scheduled for routine surgery were randomly allocated to one of three groups to evaluate trauma and postoperative complications after insertion of the Combitube, tracheal tube or laryngeal mask airway. Insertion of the Combitube was associated with a higher incidence of sore throat (48% vs. 16% vs. 12% [p < 0.01]) and dysphagia (68% vs. 12% vs. 8% [p < 0.01]) compared with tracheal intubation or insertion of the laryngeal mask airway, respectively. Hoarseness was significantly less common in both the Combitube and the laryngeal mask groups (both 12%) than in the tracheal tube group (44%; p < 0.01). Haematoma occurred in 36% of the Combitube group compared with 4% in both the laryngeal mask and the tracheal tube groups (p < 0.01). The higher incidence of complications should be considered when using the Combitube.