Biomedical subjects

Thomas Paul

Publications and source records attributed to Thomas Paul.

At least 19 recordsLinked to original sources

PubMed2007

[Compulsory treatment in anorexia nervosa].

Anorexia nervosa is a psychiatric disorder with a very high mortality rate. If the eating disorder reaches life-threatening severity, for example through a body mass index lower than 13 kg/m (2), the possibility of compulsory treatment has to be considered. However, civil commitment of patients and forced feeding against their will may reduce self confidence and self esteem. This impedes the important goal of motivating patients to undergo psychotherapy. Furthermore, compulsory treatment is regarded as a contravention of the patient's physical inviolability as enshrined in the German Constitution. Up to now only a few studies about the use of guardianship legislation for anorexia nervosa have been published. The present paper reviews psychiatric literature and significant judgements of German courts on this topic. It finishes by examining clinical issues on forced feeding and possible consequences for psychotherapy.

Anorexia Nervosa↗

PubMed2006

Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.

Adult↗

PubMed2006

Interventional atrial septal defect closure using a totally bioresorbable occluder matrix: development and preclinical evaluation of the BioSTAR device.

OBJECTIVES: We sought to test the hypothesis that interventional atrial septal defect (ASD) closure can be performed safely and effectively using a bioresorbable occluder matrix. BACKGROUND: The ideal septal occluder scaffold should promote the healthiest and most complete healing response while eventually facilitating the full resorption of the material and leaving "native" tissue behind, thus minimizing the potential for future complications from chronic foreign body and maintaining the possibility for later unobstructed transseptal access to the left atrium. METHODS: The STARFlex occluders (NMT Medical Inc., Boston, Massachusetts) were modified by substituting the conventional polyester fabric for a bioengineered, acellular type-I collagen matrix derived from porcine submucosa with a heparin-coated surface (BioSTAR occluder, NMT Medical Inc.). Comparative transcatheter closure of ASDs was performed in young sheep (n = 36). Gross pathology and histopathology were obtained after follow-up periods ranging from 7 days to 2 years. RESULTS: The STARFlex (control) devices were encapsulated time-dependently by ingrown fibrous tissue. Histology showed a mild but chronically persisting foreign body reaction. By contrast, BioSTAR devices exhibited a mild-to-moderate transient cellular immune response. Heparin coating of the BioSTAR surface improved the biocompatibility of the device by reducing surface thrombogencity. A remodeling process of the collagen scaffold, starting after 30 days in vivo, resulted in the full replacement of the matrix by host tissue after 2 years of follow-up. CONCLUSIONS: The BioSTAR device is the first septal occluder with a totally bioresorbable matrix that is fully replaced by host tissue during the healing process. The promising results of this study support testing of the BioSTAR device in clinical trials.

Absorbable Implants↗

PubMed2006

Gene expression of the Na-Ca2+ exchanger, SERCA2a and calsequestrin after myocardial ischemia in the neonatal rabbit heart.

BACKGROUND: Neonatal hearts are less susceptible to developing myocardial dysfunction after hypoxia and/or ischemia than adult hearts. Differences in intracellular calcium homeostasis may be responsible for reduced calcium overload of the immature myocardium leading to the observed protection against ischemia. OBJECTIVE: To assess differences in baseline and post-ischemic gene expression of calcium handling proteins after ischemia in neonatal and adult rabbit hearts. METHODS: We used isolated antegrade perfused rabbit hearts (age 2 days, 28 days, n = 32), which were exposed to ischemia and hypothermia simulating myocardial stunning comparable to neonatal asphyxia. Gene and protein expression of the sodium-calcium exchanger (NCX), the sarco-endoplasmatic reticulum Ca2+-ATPase 2a (SERCA) and calsequestrin (CSQ) were measured using quantitative real-time PCR and Western blotting. RESULTS: After ischemia and reperfusion in neonatal and adult hearts, a significant decrease in myocardial performance was recorded. At the mRNA level, significant differences in the baseline expression of NCX, SERCA and CSQ between neonatal and adult hearts were observed. In neonatal post-ischemic hearts, NCX and CSQ expression were significantly higher at the mRNA level than in controls. In contrast, SERCA expression remained unchanged in neonatal hearts and decreased in adult hearts compared to the non-ischemic controls. CONCLUSION: These findings suggest that changes in gene expression of calcium handling proteins may be involved in the different susceptibility of neonatal compared to adult hearts to developing myocardial dysfunction after ischemia.

Animals↗

PubMed2006

Test-retest reliability of the Eating Disorder Inventory 2.

OBJECTIVE: This study reports on findings concerning the test-retest reliability of the Eating Disorder Inventory 2 (EDI-2). METHODS: Three hundred twenty-seven female inpatients who met the DSM-IV criteria for eating disorders (anorexia nervosa, bulimia nervosa, or eating disorders not otherwise specified) and 209 inpatients with a diagnosis of depression, obsessive-compulsive disorder, anxiety disorder, or somatoform disorder took part in the study. The EDI-2 was administered to the patients at the beginning of inpatient therapy and a second time 7 days later. RESULTS: All 11 EDI-2 subscales showed significant test-retest correlations ranging from .81 to .89 in the eating disorder group and from .75 to .94 in the group with other diagnoses. DISCUSSION: The test-retest reliabilities for the EDI-2 subscales are relatively high, indicating a good and acceptable stability over time. These results provide further evidence that the EDI-2 is an instrument with good reliability for the assessment of eating disorder symptoms.

Adult↗

PubMed2006

ICD Implantation in infants and small children: the extracardiac technique.

BACKGROUND: There is no clear methodology for implantation of an internal cardioverter-defibrillator (ICD) in infants and small children. The aim of this study was to assess efficacy and safety of an extracardiac ICD implantation technique in pediatric patients. PATIENTS AND METHODS: An extracardiac ICD system was implanted in eight patients (age: 0.3-8 years; body weight: 4-29 kg). Under fluoroscopic guidance a defibrillator lead was tunneled subcutaneously starting from the anterior axillar line along the course of the 6th rib until almost reaching the vertebral column. After a partial inferior sternotomy, bipolar steroid-eluting sensing and pacing leads were sutured to the atrial wall (n = 2) and to the anterior wall of the right ventricle (n = 8). The ICD device was implanted as "active can" in the upper abdomen. Sensing, pacing, and defibrillation thresholds (DFTs) as well as impedances were verified intraoperatively and 3 months later, respectively. RESULTS: In seven of eight patients, intraoperative DFT between subcutaneous lead and device was <15 J. In the eighth patient ICD implantation was technically not feasible due to a DFT >20 J. During follow-up (mean 14.5 months) appropriate and effective ICD discharges were noted in two patients. DFT remained stable after 3 months in four of six patients retested. A revision was required in one patient due to lead migration and in another patient due to a lead break. CONCLUSIONS: In infants and small children, extracardiac ICD implantation was technically feasible. Experience and follow-up are still limited. The course of the DFT is unknown, facing further growth of the patients.

Arrhythmias, Cardiac↗

PubMed2005

Determinants of plasma adiponectin levels in patients with anorexia nervosa examined before and after weight gain.

OBJECTIVE: To examine the determinants of adiponectin levels (i) in 23 women with anorexia nervosa (mean BMI 15.0 +/- 1.2) and 43 healthy normal weight females (mean BMI 22.3 +/- 2.3; cross-sectional design) as well as (ii) after six and twelve weeks of weight gain in subgroups of 18 and 11 anorectic patients (mean weight gain 5.8 kg; longitudinal design). Plasma adiponectin and leptin concentrations were measured and their relationships to body composition (fat mass by bioelectrical impedance analysis and anthropometrics), different hormones and metabolic parameters (insulin, ACTH, cortisol, glucose, FFA, lipid profile) were investigated. RESULTS: In anorectic patients, adiponectin levels were higher (+29 %) and leptin levels were lower (-75 %) than in control subjects. There was a high variance in adiponectin levels in patients ranging from 2.6 to 18 nM. Combining patients and controls, an inverse linear correlation was observed between adiponectin levels and fat mass (r = -0.36, p < 0.05), while a positive exponential relation was found between leptin levels and fat mass (r = 0.82, p < 0.001). In anorectic patients, there were no significant correlations between adiponectin and hormonal or metabolic parameters. Weight gain resulted in increasing leptin (+0.17 +/- 0.12 nM; p < 0.001) and a nonsignificant decrease in adiponectin concentrations (-1.12 +/- 2.51 nM). Changes in leptin levels were mainly explained by a gain in fat mass (r = 0.85, p < 0.001). In contrast, changes in adiponectin levels were closely linked to initial adiponectin levels (r = -0.84, p < 0.001) but not to changes in fat mass or BMI. CONCLUSION: Cross-sectionally serum adiponectin concentration followed a linear inverse function with fat mass when patients and controls were combined. Longitudinally gain in fat mass was not associated with changes in adiponectin levels suggesting other yet unidentified influences on adiponectin secretion in anorexia nervosa.

Adiponectin↗

PubMed2005

Changes in expression levels of genes involved in fatty acid metabolism: upregulation of all three members of the PPAR family (alpha, gamma, delta) and the newly described adiponectin receptor 2, but not adiponectin receptor 1 during neonatal cardiac development of the rat.

UNLABELLED: During neonatal cardiac development, the heart changes its substrate preference from glucose to fatty acids. The aim of this study was to investigate the changes in mRNA expression levels of genes involved in the control of cardiac fatty acid metabolism in the transition from neonatal to adult life. METHODS: mRNA expression levels for peroxisome proliferator activated receptor (PPAR) alpha, gamma and delta, PPARgamma co-factor 1 alpha and beta (PGC-1 alpha and beta), 9-cis retinoc-acid-activated receptor alpha, beta and gamma (RXR alpha, beta, gamma), 5'-AMP activated protein kinase (AMPK) alpha1 and alpha2, adiponectin receptor 1 and 2 (AR 1 and AR 2) were measured in heart tissue of neonatal 0-day, 7-day and 21- day old rats. RESULTS: mRNA expression of all three members of the PPAR family were upregulated significantly from day 0 to day 21 (alpha +117%, gamma +133%, delta +203%). In addition, m-RNA expression of all RXR isoforms increased from day 0 to day 7 (alpha +125%, beta +69%; gamma +41%). AR 2 exhibited a small but significant increase in mRNA expression (+ 46%). CONCLUSIONS: We were able to demonstrate for the first time that in addition to PPARalpha, also PPARgamma and delta, as well as all RXR isoforms and AR 2 are upregulated in the heart during neonatal development.

Animals↗

PubMed2005

Retrograde use of the Cardioseal/Starflex occluder device.

The Cardioseal/Starflex septal occluder is usually deployed through a long transvenous sheath for closure of atrial septal defects, persistent foramen ovale, and, less commonly, ventricular septal defects. We describe two patients with residual left-to-right shunting after surgical palliation of congenital heart defects and illustrate the successful use of the double-umbrella device in these situations using a retrograde transarterial approach. This is exemplified by two previously not described interventions: retrograde closure of a large muscular ventricular septal defect in a patient after a palliative Mustard operation and a transcatheter closure of a Waterston-Cooley anastomosis. Effective and safe closure of left-to-right shunting can be achieved by retrograde use of the Cardioseal/Starflex device in selected adolescents and grown-ups with congenital heart disease.

Adolescent↗

PubMed2005

Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery.

BACKGROUND: Leptin has been considered a starvation hormone, but its role in malnourished patients is unknown. OBJECTIVE: We aimed to characterize the role of leptin in metabolic adaptation in women with anorexia nervosa (AN). DESIGN: In a cross-sectional study, 57 women with AN [mean (+/-SD) body mass index (kg/m(2)) on admission: 15.2 +/- 1.5] were compared with 49 healthy, normal-weight women (mean body mass index: 22.3 +/- 2.3). Nineteen patients were reinvestigated during weight gain 43 and 84 d after baseline. We measured serum concentrations of leptin, soluble leptin receptor, insulin, ghrelin, and thyroid hormones [thyrotropin, triiodothyronine (T(3)), and thyroxine]; fat mass (FM) and fat-free mass (FFM); resting energy expenditure (REE); energy intake; and eating behavior. RESULTS: Compared with values in the control women, leptin, T(3), REE, FM, and FFM were lower in the women with AN, but the leptin secretion rate was not significantly different. Leptin correlated with FM (r = 0.83, P < 0.001), T(3) (r = 0.68, P < 0.001), respiratory quotient (r = -0.47, P < 0.001), and REE (r = 0.58, P < 0.001). The association with REE weakened after adjustment for FFM and disappeared after further adjustment for T(3). Hunger and appetite had positive, whereas satiety and restraint had negative, associations with leptin. During weight gain (9.0 +/- 3.3 kg in 84 d), serum leptin and the leptin secretion rate increased. Changes in leptin secretion were associated with energy intake and REE. The initial changes in the leptin secretion rate (ie, the difference between baseline and 43 d) were negatively associated with changes in body weight from 43 to 84 d. CONCLUSIONS: Leptin contributes to metabolic adaptation in women with AN. The leptin response is associated with weight gain.

Adolescent↗

PubMed2005

Efficacy and safety of cryoenergy in the ablation of atrioventricular reentrant tachycardia substrates in children and adolescents.

INTRODUCTION: Cryoenergy has evolved as a safe and effective alternative for ablation of arrhythmia substrates in adult patients. Due to two specific features, cryomapping and cryoadhesion, this technique appears very attractive for pediatric patients minimizing complications and fluoroscopy time. The aim of the study was to investigate efficacy and safety of cryoenergy in the ablation of supraventricular tachycardia (SVT) substrates in pediatric patients. PATIENTS AND METHODS: Thirty-two patients (mean age: 10.1 +/- 3.5 years) with SVT (accessory pathways: n = 19; atrioventricular nodal reentrant tachycardia (AVNRT): n = 13) underwent electrophysiological study under the guidance of the LocaLisa system. Cryomapping at -30 degrees C was performed to predict cryoablation outcome and to ascertain AV conduction. Cryoenergy was delivered subsequently at the same spot (cryoablation at -70 degrees C) as verified by the LocaLisa system. RESULTS: Successful cryoablation was achieved in 24 of 32 patients (75%). A median of two (1-10) cryoablations were delivered. In the remaining 8 patients, radiofrequency (RF) current application was effective in 5 resulting in an overall success rate of 90.6%. In 4 patients with an accessory pathway cryomapping was not predictive for successful cryoablation (negative predictive value 66.6%). In 3 additional patients with AVNRT transient high-grade AV block occurred during cryoablation despite previous "safe" cryomapping at the same location. No other major complications were noted. CONCLUSION: Cryoablation of SVT substrates in pediatric patients was associated with a lower success rate compared to RF catheter ablation. Cryomapping decreased the number of permanent lesions but did not predict cryoablation outcome in all tachycardia substrates.

Adolescent↗

PubMed2005

L-tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain.

OBJECTIVE: We aimed to define the effect of L-3,5,3'-tri-iodothyronine (T(3)) on metabolic adaptation in underweight patients with anorexia nervosa (AN) as well as during weight gain. METHODS: This involved clinical investigation of 28 underweight patients with AN, who were compared with 49 normal-weight controls. A subgroup of 17 patients was followed during weight gain. Resting energy expenditure was measured by indirect calorimetry. Body composition was measured by anthropometry as well as bioelectrical impedance analysis. Energy intake (EI) was assessed by a 3-day dietary record. Plasma concentrations of thyroid hormones (thyroxine (T(4)), T(3) and thyrotropin (TSH)) were analyzed by enzyme immunoassays. RESULTS: When compared with normal-weight women, underweight patients with AN had reduced fat mass (FM) (-71.3%), fat-free mass (FFM) (-13.1%), resting energy expenditure (REE) (-21.8%), T(3)- (-33.4%) and T(4)-concentrations (-19.8%) at unchanged TSH. REE remained reduced after adjustment for FFM (-24.6%). T(3) showed a close association with REE. This association remained after adjustment of REE for FFM. Treatment of underweight AN patients resulted in a mean weight gain of 8.3 kg. This was mainly explained by an increase in FM with small or no changes in FFM. REE and T(3) also increased (+9.3% and +33.3% respectively) at unchanged TSH and T(4). There was a highly significant association between weight gain-induced changes in T(3) and changes in adjusted REE (r = 0.78, P < 0.001, based on Pearson's correlation). An increase in plasma T(3) concentrations of 1.8 pmol/l could explain an increase in REE of 0.6 MJ/day (that is, a 32% increase in T(3) was associated with a 13% increase in REE). CONCLUSIONS: Our data provide evidence that the low T(3) concentrations add to metabolic adaptation in underweight patients with AN. During weight gain, increases in T(3) are associated with increases in REE, which is independent of FFM. Both results are evidence for a physiologic role of T(3) in modulation of energy expenditure in humans.

Adaptation, Physiological↗

PubMed2004

Specificity of self-concept disturbances in eating disorders.

OBJECTIVES: The current study examined self-concept deficits among three diagnostic groups of eating-disordered patients, evaluated the relationship between self-concept deficits and depression, and addressed the specificity of self-concept deficits in eating-disordered patients. METHOD: Three groups of eating-disordered patients (anorexia nervosa, N = 33; bulimia nervosa, N = 38; binge eating disorder, N = 28) were first compared to three matched healthy control groups and then to two psychiatric comparison groups (patients with anxiety disorders, N = 37; patients with depressive disorders, N = 37). RESULTS: All three groups of eating-disordered patients displayed lower self-esteem and higher feelings of ineffectiveness compared with the healthy controls, even after controlling for depression. Differences in self-esteem and ineffectiveness were also found between eating-disordered patients and psychiatric controls. However, not all of the differences were significant. In addition, the psychiatric controls also exhibited lower self-esteem than normative samples. DISCUSSION: Findings suggest that self-concept deficits are more pronounced in eating-disordered patients but cannot be regarded as highly specific.

Adult↗

PubMed2004

Radiofrequency catheter ablation in small children: relationship of complications to application dose.

Little data exists to support the use of procedural modifications during radiofrequency catheter ablation (RFCA) in small children. A single institution database was reviewed for patients under 15 kg undergoing RFCA from January 1998 to August 2001. Of 268 RFCA procedures, 18 were done in 14 patients under 15 kg (median weight 5.7 kg, 3.5-13.7; age 5.8 months, 1.2-19.8). Six patients had normal hearts, 4 had congenital heart disease, and 4 patients had cardiomyopathy. Diagnoses were orthodromic reciprocating tachycardia (ORT) in nine patients/nine studies, chaotic atrial tachycardia (CAT) in one patient/two studies, and VT in four patients/seven studies. RFCA variables included maximum temperature (69 degrees C, 50-78), total applications (10, 2-21), applications > 20 seconds (5, 0-15), and total application time (331 s, 26-1,006 s). Complications were pericardial effusion in 1 patient, mild mitral regurgitation in 1, and myocardial infarction in 1 patient. When indexed for weight, the number of applications with a duration > 20 seconds in the ORT group was significantly greater in complicated versus uncomplicated procedures (0.7 applications/kg vs 0.16 applications/kg, P = 0.05). In addition, for the ORT subgroup, the indexed total application time trended higher in complicated versus uncomplicated procedures (40.6 s/kg, vs 6.6 s/kg, P = 0.1). RFCA success was 9/9 in ORT, 6/7 in VT, and 0/2 in CAT. RFCA can be successful in small children; however, complications appear to be related to RF dose indexed for body size. Thus, the decision to proceed with RFCA, and the application duration and number should be guided by patient size, balanced against the risks of the arrhythmia, and reserved for dire circumstances.

Body Weight↗

PubMed2004

High incidence of appropriate and inappropriate ICD therapies in children and adolescents with implantable cardioverter defibrillator.

Appropriate and inappropriate therapies of implantable cardioverter defibrillators have a major impact on morbidity and quality of life in ICD recipients, but have not been systematically studied in children and young adults during long-term follow-up. ICD implantation was performed in 20 patients at the mean age of 16 +/- 6 years, 11 of which had prior surgical repair of a congenital heart defect, 9 patients had other cardiac diseases. Implant indications were aborted sudden cardiac death in six patients, recurrent ventricular tachycardia in 9 patient, and syncope in 5 patients. Epicardial implantation was performed in 6 and transvenous implantation in 14 patients. Incidence, reasons and predictors (age, gender, repaired congenital heart disease, history of supraventricular tachycardia, and epicardial electrode system) of appropriate and inappropriate ICD therapies were analyzed during a mean follow-up period of 51 +/- 31 months range 18-132 months. There were a total 239 ICD therapies in 17 patients (85%) with a therapy rate of 2.8 per patient-years of follow-up. 127 (53%) ICD therapies in 15 (75%) patients were catagorized as appropriate and 112 (47%) therapies in 10 (50%) patients as inappropriate, with a rate of 1.5 appropriate and 1.3 inappropriate ICD therapies per patient-years of follow-up. Time to first appropriate therapy was 16 +/- 18 months. Appropriate therapies were caused by ventricular fibrillation in 29 and ventricular tachycardia in 98 episodes. Termination was successful by antitachycardia pacing in 4 (3%) and by shock therapy in 123 episodes (97%). Time to first inappropriate therapy was 16 +/- 17 months. Inappropriate therapies were caused by supraventricular tachycardia in 77 (69%), T wave oversensing in 19 (17%), and electrode defect in 16 episodes (14%). It caused shocks in 87 (78%) and only antitachycardia pacing in 25 episodes (22%). No clinical variable could be identified as predictor of either appropriate or inappropriate ICD therapies. There is a high rate of ICD therapies in young ICD recipients, the majority of which occur during early follow-up. The rate of inappropriate therapies is as high as 47% and is caused by supraventricular tachycardia and electrode complications in the majority of cases. Prospective trials are required to establish preventative strategies of ICD therapies in this young patient population.

Adolescent↗

PubMed2003

Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study.

OBJECTIVE: To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation. DESIGN: Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO(2)/FIO(2) at 48 h, secondary endpoints: PaO(2)/FIO(2) at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant. SETTING: Multicenter study in 19 reference centers for ARDS. PATIENTS: Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12-120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study. INTERVENTIONS: Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO(2)/FIO(2) ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO(2)/FIO(2) did not increase by 20%). A second equivalent dose within 48 h was permitted. RESULTS: In the pilot study the PaO(2)/FIO(2) increased by a mean of 100 at 48 h (n=19). A higher PaO(2)/FIO(2) ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO(2)/FIO(2) in favor of surfactant at 48 h was found in the subgroup with an initial PaO(2)/FIO(2) ratio higher than 65 and in patients without pneumonia. CONCLUSIONS. Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO(2)/FIO(2) ratio higher than 65

Acute Disease↗

PubMed2003

Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival.

Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from nonmetastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.

Adult↗

PubMed2003

Oxidative damage to a supercoiled DNA by water soluble peroxyl radicals characterized with DNA repair enzymes.

Earlier work (Paul, T., et al. (2000) Biochemistry 39, 4129-4135) has demonstrated that the water soluble positively charged peroxyl radical, (H(2)N)(2)(+)CC(CH(3))(2)OO(*) ((+)AOO(*)), caused direct strand scission of the Escherichia coli plasmid supercoiled DNA, pBR 322, with ca. 50% scission occurring at a (+)AOO(*)/base pair (bp) ratio of 0.2. There was no measurable direct scission with a negatively charged peroxyl ((-)BOO(*)) at (-)BOO(*)/bp = 24, nor with a neutral peroxyl (COO(*)) at COO(*)/bp = 5. Base modification (BM) of the same DNA by the same peroxyls has now been investigated using four base excision repair (BER) glycosylases. At (+)AOO(*)/bp = 0.04, there is 10% direct strand scission, and the Fpg protein recognized an additional 25% BM, while endonuclease (Endo) IV recognized an additional 20% BM and the other two BER enzymes did not give statistically significant BMs. None of the BER enzymes showed BMs in the DNA treated with -BOO(*). However, Fpg and Endo IV showed that at COO(*)/bp = 3.4 there was a BM comparable to that observed at (+)AOO(*)/bp = 0.04. Thus, COO(*) radicals are only ca. 1.2% as reactive toward the DNA's bases as (+)AOO(*). These results underline the importance of Coulombic forces in DNA reactions. It is also proposed that (+)AOO(*) has a higher intrinsic reactivity in H-atom abstractions and electron transfer processes than (-)BOO(*) or COO(*) radicals.

Amidines↗