Application of a new segmentation tool based on interactive simplex meshes to cardiac images and pulmonary MRI data

RATIONALE AND OBJECTIVES: Medical image segmentation is still very time consuming and is therefore seldom integrated into clinical routine. Various three-dimensional (3D) segmentation approaches could facilitate the work, but they are rarely used in clinical setups because of complex initialization and parametrization of such models. MATERIALS AND METHODS: We developed a new semiautomatic 3D-segmentation tool based on deformable simplex meshes. The user can define attracting points in the original image data. The new deformation algorithm guarantees that the surface model will pass through these interactively set points. The user can directly influence the evolution of the deformable model and gets direct feedback during the segmentation process. RESULTS: The segmentation tool was evaluated for cardiac image data and magnetic resonance imaging lung images. Comparison with manual segmentation showed high accuracy. Time needed for delineation of the various structures could be reduced in some cases. The model was not sensitive to noise in the input data and model initialization. CONCLUSIONS: The tool is suitable for fast interactive segmentation of any kind of 3D or 3D time-resolved medical image data. It enables the clinician to influence a complex 3D-segmentation algorithm and makes this algorithm controllable. The better the quality of the data, the less interaction is required. The tool still works when the processed images have low quality.     

Co-morbid health conditions at mid-life in the Iowa adoptees

Adverse health effects due to alcohol and illicit drug abuse and dependence have been well documented. This study examines the effect of substance misuse on five major groups of health conditions using a sample of well characterized adoptees. The sample consisted of 742 adoptees interviewed in the last wave of the Iowa Adoption Studies. Death rate analyses included an additional 34 participants who had died prior to the last follow-up. Substance use patterns and medical history were assessed using the SSAGA-II (Bucholz, K. K., Cadoret, R. J., Cloninger, C. R., Dinwiddie, S. H., Hesselbrock, V. M., Nurnberger, J. L., Jr., et al. (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol, 55 (2), 149-158). Subjects were divided into three groups according to DSM-IV diagnostic criteria, controls, alcohol abuse or dependence only (alcohol only), and the Alcohol-Drug group (abuse or dependence diagnosis on at least one illicit substance with or without alcohol diagnosis). Incidence rates of various diseases were measured using logistic regression. Survival analyses were used to examine whether substance abusers developed cardiovascular or metabolic disease at an earlier age than control subjects. Diagnostic grouping made no difference in the incidence rates or age of onset of health conditions. The amount of alcohol consumed by males significantly predicted higher number of overall health complaints as well as higher incidence rates of cardiovascular disease. The amount of illicit drug exposure did not predict an earlier age of diagnosis for cardiovascular or metabolic disease. Individuals in the Alcohol-Drug group had an increased incidence of deaths than either the alconly or the control groups.     

Effects of inpatient rehabilitation on health-related quality of life in breast cancer patients.

BACKGROUND: Major endpoint for the assessment of a complex inpatient rehabilitation program is the health-related quality of life. In a prospective longitudinal study we evaluated the subjective well-being of breast cancer patients by different methods. PATIENTS AND METHODS: 183 breast cancer patients were asked to complete six different questionnaires at three different time points: t1: start of treatment, t2: end of treatment, t3: 3 months after t2. RESULTS: In the Hospital Anxiety and Depression Scale (HADS-D) we observed high mean scores for anxiety (8.73) and depression (5.55), as compared to a healthy control population (5.8 and 3.34, respectively). There was a significant improvement for both scores at t2 (6.84 and 4.77, respectively) and for anxiety at t3 (7.68). This was confirmed by the FBK questionnaire showing a significant decrease of the psychological distress in the t1/t2 and t1/t3 time periods as well. The global health score of the QLQ-C30 instrument increased significantly at the end of the rehabilitation and was maintained at the 3-month follow-up. This was true for most of the functional subscales as well. Older widowed women with 3-4 accompanying diseases had the most profit from the program. Using the Perceived Adjustment to Chronic Illness Scale (PACIS), we observed significantly less effort of coping with the illness at t2 and t3. CONCLUSIONS: At the end of a complex rehabilitation program for breast cancer patients, the health-related quality of life improved in several domains. While after a 3-month follow-up the scores were still better than before the treatment, anxiety and depression increased again. Therefore, the good results of the rehabilitation program should be maintained by continuous ambulatory treatment.     

Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia

Background: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3‐ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3‐ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. Patients and methods: We retrospectively analysed the prevalence of NPM1 and Flt3‐ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60–85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow‐up of surviving patients was 600 d. Results: Sixty‐seven patients were tested negative for NPM1 and Flt3‐ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3‐ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2, P = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log‐rank test P = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3‐ITD mutation had a significant worse overall survival compared to wildtype patients (P = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%, P = 0.91). Conclusion: As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose‐reduced conditioning) should be considered for these patients in first CR.     

Mechanobiological oscillators control lymph flow

The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, “emergent” behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled—at least in part—by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca²⁺-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca²⁺ and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function.Flow of fluid within the lymphatic system is central to many aspects of physiology, including fluid homeostasis and immune function, and poor lymphatic drainage results in significant morbidity in millions of patients each year (1). Although it is known that various mechanical and chemical perturbations can affect lymphatic pumping, there are still no pharmacological therapies for lymphatic pathologies. A fundamental understanding of how various signals coordinate lymphatic vessel function is a necessary first step toward development of treatments to restore fluid balance and enhance immunosurveillance.The lymphatic system consists of fluid-absorbing initial lymphatic vessels that converge to collecting lymphatic vessels, which transport lymph through lymph nodes and back to the blood circulation (2). The collecting lymphatic vessels actively transport fluid via contractions of their muscle-invested walls. Unidirectional flow is achieved by intraluminal valves that limit back flow. Unfortunately, lymphatic pumping is not always operational, and this can lead to lymphedema and immune dysfunction (3, 4).Much is known about the mechanisms responsible for the contractions of the vessel wall. As in blood vessels, the muscle cells that line lymphatic vessels respond to changes in Ca²⁺ concentration. Membrane depolarization results in an influx of Ca²⁺ to initiate the contractions, and this process can be modulated by neurotransmitters (5) or inflammatory mediators, which generally alter the frequency and amplitude of lymphatic pumping (4, 6). Many studies have also reported that physical distension, either by applying isometric stretch or by pressurizing the vessel can affect the phasic contractions (7–10). Interestingly, endothelial (11) and smooth muscle cells (12) have stretch-activated ion channels that can initiate Ca²⁺ mobilization in response to mechanical stresses. Thus, stretch may constitute an important trigger for the contraction phase of a pumping cycle.There are also complementary mechanisms for tempering the Ca²⁺-dependent contractions. The most notable is nitric oxide (NO), a vasodilator that acts at multiple points in the Ca²⁺-contraction pathway to modulate Ca²⁺ release and uptake, as well as the enzymes responsible for force production (13). Blocking or enhancing NO activity can dramatically affect pumping behavior (4, 14–17). Furthermore, lymphatic endothelial cells produce NO in response to fluid flow (16, 18, 19). Importantly, NO dynamics are faster than observed pumping frequencies, so flow-induced NO production is another potential mechanosignal involved in lymphatic regulation (20).     

Relation between N-terminal pro-brain natriuretic peptide values and invasively measured left ventricular hemodynamic indices

BACKGROUND:

Pro-brain natriuretic peptide (proBNP) is synthesized in the left ventricle. In response to transmural pressure, it is secreted into the circulation and consequently cleaved to yield the active hormone BNP and its N-terminal fragment (NT-proBNP). Determination of NT-proBNP is used as an aid in the diagnosis of left ventricular dysfunction.

METHODS:

We analyzed NT-proBNP-levels before left-heart catheterization in 115 patients. At the end of the study, we compared the NT-proBNP values to the invasively measured hemodynamic indices (left ventricular ejection fraction, maximum change in pressure over time [dP/dt_max] and left ventricular end-diastolic pressure) and the clinically observed New York Heart Association (NYHA) classifications.

RESULTS:

A significant (P=0.008) increase of the NT-proBNP values was observed in cases of low ejection fraction (less than 41%). Furthermore, a significant (P=0.03) increase of the NT-proBNP values was measured in cases of heavily reduced dP/dt_max (less than 1500 mmHg/s). The increase of NT-proBNP values in cases of high end-diastolic pressures was distinct but not significant. In the clinical observation (NYHA classification), a significant increase of NT-proBNP levels corresponded to increasing severity of heart failure. However, a large standard deviation was seen in all groups.

CONCLUSION:

Concerning low ejection fractions, a high end-diastolic pressure and strong reduced dP/dt_max in all cases an increase of pro-BNP-values was seen. However, the partly reported strong correlation of the BNP value to the left ventricular ejection fraction, dP/dt_max and left ventricular end-diastolic pressure results was not found in the cases of middle and moderate heart failure, in contrast to the clinical observation. Regarding the large standard deviation, it may be possible to discriminate an unfavourable course of heart failure in an early stage.     

Right ventricular obstruction in various types of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is most probably a genetically transmitted disease with different clinical and hemodynamic features. In hypertrophic obstructive cardiomyopathy (HOCM) the obstruction is predominantly in the left ventricular outflow tract (IHSS). In a minority of cases the obstruction is strictly located in midventricle (midventricular obstruction, MO). Hypertrophic nonobstructive cardiomyopathy (HNCM) includes asymmetric septal hypertrophy (ASH) and apical hypertrophy (AH). Right ventricular hypertrophic obstruction (RVHO) is an uncommon type of HCM and is almost always combined with other types of left ventricular HCM. We describe in the present report 1 case of RVHO with IHSS, 2 cases with MO and, to our knowledge, the first case with AH.     

Metabolism of sulfur-containing amino acids in the dermatophyte Microsporum gypseum. I. Neutral amino acids

The dermatophyte Microsporum gypseum was cultivated on a glucose-arginine medium to which on out of six sulfur-containing amino acids was added (L-cystine, L-djenkolic acid, DL-lanthionine DL-homocystine, L-methionine, or L-methionine-sulfone at a concentration of 5 mM with respect to sulfur content). The addition of these substances did not stimulate the growth and some amino acids (djenkolic acid and particularly methionine and methionine-sulfone) were inhibitory. All tested compounds were utilized during the growth not only as sulfur source but as a source of carbon and nitrogen as well. In four substrates excess sulfur was excreted after oxidation into the medium in the form of sulfate. Small amounts of sulfite were also observed. It usually reacted with remaining disulfides in the medium forming S-sulfo compounds (R-S.SO3H). Cystine and djenkolic acid were oxidized rapidly and completely. In contrast, lanthionine and particularly homocystine were oxidized slowly and only after a longer adaptation. To some extent lanthionine was already oxidized extracellularly in the medium. With methionine and its sulfone, excess sulfur was not removed by oxidation but by demethiolation to methane thiol and further volatile products.     

Chronic traumatic tricuspid insufficiency

Isolated tricuspid insufficiency (TI) is relatively uncommon and mostly of traumatic origin. We report clinical noninvasive and invasive findings and surgical results in 5 cases. All patients had complete clinical, noninvasive and invasive studies including right and left catheterization, and coronary angiographies in 3 patients. All but 1 patient had nonpenetrating trauma. All had large jugular V waves, right precordial impulse, systolic liver pulse, positive Carvallo sign documented also by noninvasive techniques. Right heart failure was present in 3 patients. Chest x-ray showed prominent right atrium and distended vena cavae. Electrocardiogram showed normal sinus rhythm in 4 patients and atrial fibrillation in 1. Two patients had right bundle-branch block, and 2 presented RSR'-pattern. Echocardiogram showed large right atrium (RA) (6-10 cm), floppy tricuspid valve (TV) in all, dilated right ventricle (RV) in 2 patients. Findings of left heart were normal in all. Three patients had right-to-left shunt. In RA A waves were 4-8, Y waves 1-3, and V waves 12-22 mmHg, respectively (mean RV and PA pressures were 23/3 and 23/10 mmHg, respectively). Four patients had anuloplasty, 2 of them repair of valve and chordae. Surgical results were good in 2 patients with valve repair, satisfactory in 1; there was significant TI resistance in 1 case. We conclude that TI has distinctive clinical findings and must be ruled out in all patients with chest trauma. Surgery must include not only anuloplasty, but, cusps and chordae must also be evaluated and reconstructed if necessary.