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Attention to resource utilization has led to increased scrutiny of the appropriateness of initial diagnostic imaging studies on the basis of current guidelines. Far less attention has been paid to examining the lack of appropriate follow-up studies.A retrospective cross-sectional analysis was performed of 3,781 consecutive outpatients referred for transthoracic echocardiography (TTE) from July to December 2008. Data from the electronic medical records were extracted to see if patients with at least moderate left-sided valvular stenosis or regurgitation underwent subsequent echocardiographic studies within 60 days of the period recommended by the 2006 American College of Cardiology and American Heart Association valve guidelines document.Of 342 outpatients with at least moderate valve dysfunction, 38 (11%) were excluded for reasons that precluded the need for a follow-up study (e.g. death, surgery). Of the remaining 304 patients, only 179 (59%) underwent follow-up echocardiography within the recommended period. Rates of timely follow-up TTE were higher when ordering physicians were cardiologists or cardiovascular surgeons (65%) compared with primary care physicians or internal medicine specialists (45%) (P.01). Follow-up rates were significantly different for aortic stenosis (77%), mitral stenosis (67%), aortic regurgitation (49%), and mitral regurgitation (49%) (P.01). Patients receiving timely follow-up TTE were younger (66 ± 15 vs 71 ± 15 years, P = .002) and more likely to be male (odds ratio, 1.79; 95% CI, 1.12-2.85; P = .01).To the authors' knowledge, this is the first study demonstrating low rates of compliance with guideline-recommended monitoring TTE in patients with at least moderate valve dysfunction. Cardiac practitioners have significantly better compliance. Strategies are needed to improve timely follow-up care in this population.

Higher hemoglobin A1c (HbA1c) is associated with lower cognitive function in type 2 diabetes. To determine whether associations persist at lower levels of dysglycemia in patients who have established cardiovascular disease, cognitive performance was assessed in the Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL-CVD) trial.The age-adjusted relationships between HbA1c and cognitive performance measured by the Mini-Mental State Examination, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency were assessed in 226 men with metabolic syndrome and established stable coronary artery disease.Of the participants, 61.5% had normoglycemia, 20.8% had impaired fasting glucose, and 17.7% had type 2 diabetes. HbA1c was associated with cognitive function tests of Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency (all P.02), but not the Mini-Mental State Examination. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA1c value was associated with a 5.9 lower Digit Symbol Substitution Test score (95% confidence interval [CI], -9.58 to -2.21; P.0001); a 2.44 lower Rey Auditory Verbal Learning Test score (95% CI, -4.00 to -0.87; P.0001); a 15.6 higher Trail Making Test score (95% CI, 5.73 to 25.6; P.0001); and a 3.71 lower Categorical Verbal Fluency score (95% CI, -6.41 to -1.01; P.02). In a multivariate model adjusting for age, education, and cardiovascular covariates, HbA1c remained associated with cognitive function tests of Rey Auditory Verbal Learning Test (R(2) = 0.27, P.0001), Trail Making Test (R(2) = 0.18, P.0001), and Categorical Verbal Fluency (R(2) = 0.20, P.0001), although association with the Digit Symbol Substitution Test was reduced.Higher HbA1c is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health.

Objective To develop a simplified method to quantify liver fat using computed tomography (CT) fat % index (CT FPI ) compared to liver spleen method (CT L/S , CT L−S ). Methods Noncontrast CT of the liver was performed in 89 patients (overweight, obese, severely obese) to quantify fat, using the following: CT FPI =[(65−patient HU)/65]×100, normal live r =65 HU. Results There was a strong linear correlation between CT FPI and the standard method of assessing liver fat using CT L/S ( r =−0.901), CT L−S ( r =−0.911). Hepatic HU and CT FPI were significantly different in the severely obese group compared to other two groups ( P Conclusion Significant correlation indicates equal diagnostic accuracy of the two methods in appropriately calibrated scanners.

Objectives The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes. Background No study has examined the effects of these genetic variants on CHD in diabetic patients. Methods We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects). Results Five single-nucleotide polymorphisms, rs4977574 ( CDKN2A/2B ), rs12526453 ( PHACTR1 ), rs646776 ( CELSR2-PSRC1-SORT1 ), rs2259816 ( HNF1A ), and rs11206510 ( PCSK9 ) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p Conclusions Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.

Background: Obesity is a risk factor for left ventricular (LV) hypertrophy and excess cardiovas- cular disease and mortality. Substantial weight loss is associated with a decrease in cardiovascular mortality. Using volumetric cardiovascular magnetic resonance (CMR) imaging, we studied changes in cardiac anatomy and systolic function in women undergoing substantial weight loss in a university hospital. Methods: A total of 17 women (body mass index (BMI) 44.1 4.2 kg/m 2 ; age 44 11 yr) scheduled for bariatric surgery underwent volumetric CMR imaging before and 3 and 17 months after surgery. Results: The body weight declined by 37.2 10.5 kg (32%) with a decrease in BMI to 29.9 4.7 kg/m 2 (32%, P.004) during 17 months of observation. The LV mass decreased from 120 23 g to 82 11 g (32%, P.004), with a linear relationship between the decrease in BMI and decrease in LV mass (P.008) for the duration of the observation period. After adjustment for systolic and/or diastolic blood pressure, the relationship remained significant (P.001). The right ventric- ular (RV) mass declined from 31.7 6.7 g preoperatively to 26.6 4.5 g at 3 months (16%, P .001) but without additional changes at 17 months. No change was found in the LV or RV end-diastolic volume or ejection fraction. Conclusion: In morbidly obese women, substantial weight loss was associated with a reduction of LV and RV mass. The decrease in LV mass was linearly related to the reduction in BMI, independent of changes in blood pressure, and might partially explain the reduction in cardiovas- cular mortality associated with substantial weight loss. The BMI was a predictor of LV mass in this population. (Surg Obes Relat Dis 2009;5:648-652.) © 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Objectives We sought to evaluate radiofrequency (RF) ablations lesions in atrial fibrillation (AF) patients using cardiovascular magnetic resonance (CMR), and to correlate the ablation patterns with treatment success.

Catheter ablation of atrial fibrillation (AF) involves extensive radiofrequency ablation (RFA) of the left atrium (LA) around the pulmonary veins. The effect of this therapy on LA function is not fully characterized.The purpose of this study was to determine whether catheter ablation of AF is associated with a change in LA function.LA and right atrial (RA) systolic function was assessed in 33 consecutive patients with paroxysmal or persistent AF referred for ablation using cardiovascular magnetic resonance (CMR) imaging. Steady-state free precession ECG cine CMR imaging was performed before and after (mean 48 days) AF ablation. All patients underwent circumferential pulmonary vein isolation using an 8-mm tip RFA catheter. High spatial resolution late gadolinium enhancement CMR images of LA scar were obtained in 16 patients.Maximum LA volume decreased by 15% (P.001), and LA ejection fraction decreased by 14% (P.001) after AF ablation. Maximum RA volume decreased by 13% (P = .018), but RA ejection fraction increased by 5% (P = .008). Mean LA scar volume was 8.1 +/- 3.7 mL. A linear correlation was observed between change in LA ejection fraction and scar volume (r = -0.75, P.001).Catheter ablation of AF is associated with decreased LA size and reduced atrial systolic function. This change strongly correlates with the volume of LA scar. This finding may have implications for postprocedural thromboembolic risk and for procedures involving more extensive RFA.

This article highlights the technical challenges and general imaging strategies for coronary MRI. This is followed by a review of the clinical results for the assessment of anomalous CAD, coronary artery aneurysms, native vessel integrity, and coronary artery bypass graft disease using the more commonly applied MRI methods. It concludes with a brief discussion of the advantages/disadvantages and clinical results comparing coronary MRI with multidetector CT (MDCT) coronary angiography.

The aim of this study was to assess, using cardiovascular magnetic resonance (CMR), whether morphologic right ventricular (RV) abnormalities are present in patients with hypertrophic cardiomyopathy (HC). Left ventricular hypertrophy has been considered the predominant phenotypic expression of HC. Whether structural abnormalities of the right ventricle are also present in HC is unknown. CMR provides complete coverage of both ventricles with high spatial resolution. CMR was applied to study RV morphology in HC. CMR was performed on 46 subjects with HC (mean age 39 +/- 16 years; 70% men) free of pulmonary hypertension and 22 healthy subjects (mean age 44 +/- 16 years; 50% men). Mass, wall thickness, chamber volume, the ejection fraction, and fibrosis were assessed for both ventricles. Maximum RV wall thickness was increased in patients with HC compared with referent controls (7 +/- 2 vs 5 +/- 1 mm, p0.001), including 15 (33%) with maximum wall thicknessesor =8 mm (or =2 SDs higher than the mean for controls) and 4 (9%) with extreme hypertrophy (or =10 mm). RV hypertrophy was predominantly a diffuse process involving the entire or a significant proportion of the RV wall in most patients (n = 8 [53%]). The RV wall mass index was also increased in patients with HC (28 +/- 9 vs 22 +/- 4 g, p0.001). A significant correlation was found between maximum RV and left ventricular wall thickness (R(2) = 0.4, p0.001) and between RV and left ventricular mass (R(2) = 0.4, p0.001). Only 1 (2%) patient with HC had evidence of RV wall fibrosis. In conclusion, morphologic RV abnormalities are present in a substantial proportion of patients with HC.

Objectives We examined whether delayed-enhancement cardiovascular magnetic resonance (DE-CMR) coronary artery wall imaging correlated with atherosclerosis detected by using multislice computed tomography (MSCT) and quantitative coronary angiography (QCA). Background The use of DE-CMR coronary vessel wall imaging may provide a noninvasive method to assess diseased coronary vessel walls. Methods We performed DE-CMR coronary artery wall imaging in 14 patients with cardiovascular risk factors and 6 healthy subjects without risk factors. Results A greater prevalence of strong DE was noted with greater MSCT evidence of disease, with DE in 2 (7%) of 30 coronary segments with no plaque by MSCT, in 1 (10%) of 10 segments with noncalcified plaque on MSCT, and in 16 (36%) of 44 segments with calcifications by MSCT (p = 0.009, adjusted p = 0.035). Delayed enhancement was observed in 8 (53%) of 15 segments with >20% coronary artery stenosis by QCA but also in 12 (15%) of 80 segments without angiographically apparent coronary disease (p = 0.004, adjusted p = 0.01). Conclusions The use of DE-CMR allowed us to identify areas of DE that correlate with severity of atherosclerosis by MSCT and QCA. This novel approach may be useful for the assessment of coronary vessel wall in patients with suspected coronary artery disease.

The “law of approach to saturation” is a well-known mathematical model for describing the behavior of ferromagnets at high magnetic field strengths which has the additional advantage that it can be linked to anisotropy through one of the terms in the mathematical expression of the law. In this paper, two recent and more comprehensive models of the magnetization process are compared with the law of approach and with each other in terms of their capability to describe the dependence of the magnetization curve in the high field regime. The comparison leads to relations between these two models and the interpretation of certain aspects of the models in terms of anisotropy. It is shown that the effects of anisotropy can be incorporated directly into these models without any additional assumptions.

Amiodarone use for the prevention of recurrent atrial fibrillation or atrial flutter requires drug loading over a period of several days to weeks, whereas class 1C agents do not. Three hundred thirty-nine patients were evaluated during drug loading with amiodarone or class 1C agents, and it was found that recurrent arrhythmia was common, usually not persistent, and frequently asymptomatic. Recurrent arrhythmia was not more common with amiodarone.

Elongated ferromagnetic nanoparticles have been formed by heavy ion irradiation of paramagnetic YCo2 thin films. The fluence affects both anisotropy and spontaneous magnetization. The measured effect on the shape of the hysteresis curve, for example initial susceptibility and coercivity, is predicted by the energetic model.

A new passive and wireless magneto-optical rotational velocity sensor is described. It is based on measuring the intensity oscillations of linearly polarized light transmitted through an orthoferrite plate and an analyzer. The plate is subjected to the action of the magnetic field of a disc whose angular velocity has to be measured. Thanks to the high velocity and smooth reproducible character of the domain wall motion in the orthoferrite plate, one can continuously measure angular velocities in a very wide range—from ultralow to the MHz range.

The non-linear dependence on history of magnetic field and magnetization in ferromagnetic materials is described by statistical domain behaviour using phenomenological parameters. These parameters are related to macroscopic hysteresis features (as coercivity, initial susceptibility, saturation, and remanence), which allows fast and easy identification. Consequently, these parameters are related to spontaneous magnetization, magnetocrystalline anisotropy, magnetostriction, and microstructure geometry, using dimensionless microscopic constants. This step allows correct interpretations of the parameter dependence and the macroscopic hysteresis on stress, temperature, and direction of magnetization. Examples of model applications are the prediction of the magnetic behaviour of thin films in magnetoresistive sensors, stress dependence of magnetization in amorphous ribbons, and Barkhausen noise.

Summary At the afforested overburden heap “Langteichhalde” (lignite mining district Berzdorf, Eastern Germany) a long-term study of the soil fauna (since 1961) was completed by new investigations between 1996–1999 taking microfauna, mesofauna and macrofauna into consideration. Detailed information about the present development of testate amoebae, nematodes, lumbricids, spiders and harvestmen, oribatids, centipedes, millipedes, apterygotes, ants, carabid and staphylinid beetles are briefly compared with the earlier succession of these groups. Generally, both the species inventory as well as diversity points to a change from open landscape communities to woodland associations, albeit in a more or less poor condition. Differences of the settlement depending on deciduous or coniferous afforestation type and surface profile (crests, troughs) are discussed. The contribution of soil organisms to organic matter decomposition was studied by bait lamina tests, the minicontainer technique, and by calculating the potential zootic decomposition level. At the deciduous afforestation the overall soil biological activity reaches the level of natural woodland soils very quickly (after 10– 20 years), even though based upon the continuing development of soil faunal entities. Primarily coniferous afforestations show an impeded decomposing activity, even if developing in a mixed wood. During succession of the mine site community an interesting interrelationship between parts of the soil fauna, especially between lumbricids and microarthropods, can be demonstrated.

The immunodominant regions of the gp41 from 13 HIV-1 subtype O strains from Cameroon, 11 from France and one from Germany were sequenced. The amino acid sequences were compared to those of the 3 published HIV-1 subtype O isolates, ANT70, MVP-5180 and VAU. All HIV-1 subtype O isolates had a very conserved amino acid sequence in this region and showed a subtype O specific structure. Within the cysteine loop there was a positive charge of two basic amino acids, arginine and lysine. Only two strains (CM.6778 and CM.8161) showed an acidic amino acid in this loop. None of the isolates showed the same amino acid sequence in this immunodominant region. A 25 residue peptide from the immunodominat domain of gp41 of the MVP-5180 strain was synthesized, cycled to form the cysteine-loop and coated to microtiter plates. Antibody binding was detected by indirect ELISA using an enzyme labeled anti-human IgG. Out of 111 anti-HIV-1 positive specimens, collected mainly from Cameroonian HIV infected patients, only 10 were not reactive in this assay. The 42 anti-HIV-1 subtype O positive specimens gave all a reaction above cut off. Despite the diversity found in the amino acid sequences within the 25 isolates a peptide-based indirect ELISA representing the immunodominant epitope of the strain MVP-5180 successfully detected all the anti-HIV-O sera so far tested, pointing to the importance of adding such a peptide for correct identification of HIV-1 subtype O infected patients, while some assays without HIV-O specific antigens partially fail to detect all anti-HIV-O specimens.

Neuroendocrine cells are present in various organ systems. These widely distributed cells as well as their histogenetically related tumours can produce various peptides and peptide hormones. From 1984 to 1993, 349 neuroendocrine tumours were found among 511,382 histological diagnoses at the Institute of Pathology of the Medical School of the Karl Franzens University in Graz. In 30% carcinoid of the appendix was diagnosed, in 16% carcinoid of the colorectum, in 9% carcinoid of the small intestine and in 2% duodenal carcinoid. Carcinoid of the stomach was detected in 14%. Seven of these cases showed microcarcinoidosis and five of them were combined with an adenocarcinoma. Carcinoid of the oesophagus was present in 1%, neuroendocrine pancreatic tumours in 6%. Neuroendocrine tumours of the bronchial system were found in 12%, medullary thyroid cancer in 5%. In 1% a Merkel-cell tumour was diagnosed. Other more rare localizations of neuroendocrine tumours were the uterus, ovary, breast, testes, epididymis, anal region and the upper respiratory tract.

Sudden cardiac death (SCD) due to ventricular arrhythmia remains a common cause of death. Several studies have demonstrated a survival benefit with implantable cardioverter-defibrillator (ICD). Unfortunately, a majority of patients receiving an ICD for primary prevention fail to utilize the device.

Hypertrophic cardiomyopathy (HCM) is the most common, heritable cardiovascular disorder and the most frequent cause of sudden cardiac death (SCD) in young adults. Gender disparities with regards to clinical outcomes among HCM patients are not well-defined. We investigated the relationship between

Objectives: In the present study, we retrospectively analyzed a cohort of 455 adult patients (222 males, 233 females) with acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (SCT) between 2000 and 2010 in Austria. Methods: The median age at time of SCT was 46 years with a range from 18 to 76 years. Conditioning therapy consisted of a myeloablative regimen (264/455 patients) or reduced intensity conditioning (RIC) (191/455 patients). In 397/455 peripheral blood stem cells (PBSC) were transplanted, 38 patients received bone marrow (BM), in 3 cases both were used, and in 17 patients a umbilical cord blood transplantation (UCBT) was performed. Results: Patients were followed up with a median observation time of 27 months. Overall survival (OS) for the entire cohort was 37%, with a median survival time of 25 months. Post-transplant relapse was documented in 134/455 patients, and 106 patients died due to the recurrence of AML resulting in a disease-free survival of 59%. Acute Graft-vsHost-Disease (GvHD) was documented in 177/360 patients. In multivariate Cox regression analysis the EBMT score was a statistical significant parameter for OS, as well as age and type of conditioning. Conclusions: Following our results, we conclude that for patients 40 years RIC should be considered.

Utilizing the dark field method, parts of different brightness within domain walls of yttrium orthoferrite have been observed. Dark segments between these parts and the dependence of their positions on an applied magnetic field indicate the presence of Bloch lines.

To the Editor: Myocardial perfusion imaging (MPI) is unique in that patients administered radioactive pharmaceuticals continue to emit radiation following study completion, with potential radiation exposure to others. Despite the wealth of data regarding increasing radiation exposure in patients

The noninvasive evaluation of the coronary arteries has been a major goal of cardiovascular imaging. This has been difficult to accomplish because the coronary arteries are small, have similar imaging characteristics to the surrounding myocardium and cardiac veins, and are in constant motion. Two

The application of a hysteresis model to the prediction of the efficiency of a high-frequency micro-transformer, operating at 5 MHz, is described. The core of the micro-transformer consists of electroplated thin films of nickel iron alloy. Measurements were carried out on both toroidal magnetic core and micro-transformers in order to validate the model.

more albumin (p < 0.01) and fibrinogen (p < 0.001) than that grown in WME. Fibronectin was secreted by NPCs in abundance and was intimately associated with EpCAM cells in vivo. EpCAM LPCs expressed fibronectin-binding integrins alpha4beta1 and alpha5beta1, suggesting fibronectin might be an important mediator for hepatocyte maturation. Conclusions: This study indicates that factor(s) secreted by NPCs play an important role in LPC proliferation and differentiation and will be useful for the development of clinically applicable cell therapy.

The use of airbags has decreased the morbidity and mortality from traffic accidents when used in conjunction with lap and shoulder seat belts [1–4]. However, case reports of injuries due to the deployment of airbags such as corneal abrasions, facial erythema, contusions, abrasions, fractures, aortic transections, heart valve injuries and loss of hearing have also been noted [5]. We report the case of an elderly front seat passenger who sustained a rupture of the inferior thyroid artery when the airbag deployed during a front-to-sideon collision. To our knowledge, this has not been previously reported.

Understanding pulmonary vein (PV) anatomy is important for the planning and execution of PV isolation for the treatment of atrial fibrillation, screening for PV stenosis after the procedure, and investigating the pathophysiology of atrial fibrillation. We hypothesized that significant changes in PV size occur during the cardiac cycle and sought to identify the relationship of data obtained with conventional non-electrocardiogram (ECG)-gated methods compared with ECG-gated measures of PV size using cardiovascular magnetic resonance.A consecutive series of 14 patients in sinus rhythm were evaluated with non-ECG-gated contrast-enhanced magnetic resonance angiography and ECG-gated cine cardiovascular magnetic resonance of the PV. Pulmonary vein diameter, perimeter, and cross-sectional area (CSA) were measured using both methods.Maximum diameter, perimeter, and CSA occurred simultaneously in all PV. The timing of the maximum size varied but generally occurred in ventricular diastole (101 +/- 112 milliseconds after mitral valve opening). The timing of minimum PV size also varied but generally occurred in ventricular systole (212 +/- 90 milliseconds before mitral valve opening). The difference between the maximum and minimum PV size was 15% +/- 8% for diameter, 15% +/- 7% for perimeter, and 27% +/- 12% for CSA (P.001 for all). Contrast-enhanced magnetic resonance angiography correlated best with the ECG-gated maximum PV size (R20.48, P.001 for all) and was greater than the minimum and average PV sizes (P.05 for all).All measures of PV size vary significantly during the cardiac cycle. Contrast-enhanced magnetic resonance angiography PV measurements correlate best with maximum PV size.

We sought to establish the safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications (AAMs) for the maintenance of sinus rhythm in patients with atrial fibrillation (AF) or atrial flutter (AFl). AAMs are frequently utilized to maintain sinus rhythm in patients with AF or AFl. Although they are often initiated in an outpatient setting, there is little prospective evidence for the safety of this approach. Patients with a history of AF or AFl were prospectively monitored with an event recorder during 409 AAM initiation trials. All AAMs were initiated in sinus rhythm. Patients transmitted a recording (30 seconds) once daily for 10 consecutive days. Amiodarone was used for 212 patients (51.8%), 127 (31.1%) received a type 1C AAM, 37 (9.0%) received sotalol, and 33 (8.1%) received a type 1A AAM. Adverse events occurred in 17 patients (3 died, 3 had bradycardia that required permanent pacemaker implantation, and 11 had bradycardia requiring a decrease in the dose of antiarrhythmic or rate-controlling medication). Most events were due to bradycardia in patients who received amiodarone. There was a significant association between amiodarone-associated bradycardia and women. The only event that occurred during the first 48 hours was an episode of bradycardia in a patient who received amiodarone and was managed as an outpatient. The outpatient initiation of AAMs for patients with a history of AF or AFl while in sinus rhythm is associated with significant risk. Most adverse events occurred beyond the usual time period for in-hospital monitoring of the initiation of AAMs.

The interaction of phosphatidylserine dispersions with “hydrophobic”, organic cations (acetylcholine, tetraethylammonium ion) is compared with that of simple inorganic cations (Na+, Ca2+); differences in the hydration properties of the two classes of ions exist in the bulk phase as evident from spin-lattice relaxation time T1, measurements. It is shown that the reaction products (cation-phospholipid) differ markedly in their physicochemical behaviour. With increasing concentration both classes of ions reduce the ζ-potential of phosphatidylserine surfaces, the monovalent inorganic cations being only slightly more effective than the hydrophobic cations. Inorganic cations cause precipitation of the lipid once the surface charge of the bilayer is reduced to a certain threshold value. This is not the case with the organic cations. The difference is probably associated with the different hydration properties of the resulting complexes. Thus binding of Ca2+ causes displacement of water of hydration and formation of an anhydrous, hydrophobic calcium-phosphatidylserine complex which is insoluble in water, whereas the product of binding of the organic cations is hydrated, hydrophilic and water soluble. The above findings are consistent with NMR results which show that the phosphodiester group is involved in the binding of both classes of cations as well as being the site of the primary hydration shell. Besides affecting interbilayer membrane interactions such as those involved in cell adhesion and membrane fusion, the binding of both classes of cation can affect the molecular packing within a bilayer.

The formation of small (100 nm) unilamellar vesicles induced by increasing the pH of dispersions of phosphatidic acid and mixtures of this with other phospholipids has been described [22]. Here it is shown that this method of vesiculation also produces small unilamellar vesicles from mixtures of phosphatidic acid with phosphatidylcholine and cholesterol, with monoolein and with monomyristin. Further, the proposal [32] that lipids that show, so called, unlimited swelling form unilameltar vesicles in excess water is confirmed. The disruption of the formation of multilamellar vesicles from egg phosphatidylcholine by the inclusion of charged amphiphiles (cholic acid, dodecyltrimethylammonium bromide and chlorpromazine) in the bilayers was followed by the decrease in light scattering and the increase in vesicles not sedimented by centrifugation. Both these changes correlate with the formation of unilamellar vesicles that can be demonstrated by electron microscopy.

Utilizing differential scanning calorimetry and x-ray diffraction, 1,2-dimyristoyl-L-glycero-3-phospho-L-serine (DMPS) was shown to form hydrated bilayer membrane structures exhibiting a gel leads to liquid crystalline transition at 39 degrees C (delta H = 7.2 kcal/mol). Addition of up to molar concentrations of the alkali halides NaCl, KCl, Rl Cl, and CsCl produced relatively minor changes in DMPS bilayer structure or stability. For example, in the presence of 0.5 M NaCl, the transition temperature (Tc = 42 degrees C) and transition enthalpy (delta H = 7.0 kcal/mol) show only minor changes. In marked contrast, addition of LiCl results in "'crystallization" of the DMPS bilayer membrane structure. At 0.5 M LiCl, the crystalline DMPS exhibits a bilayer gel leads to liquid crystal transition at 89 degrees C accompanied by a high enthalpy change, delta H = 16.0 kcal/mol. Thus, Li+ induces an isothermal crystallization of DMPS bilayers, the hydrocarbon chains adopting a more ordered packing mode than the "hexagonal" arrangement of the gel state. In view of the widespread use of lithium in the treatment of manic-depressive illness, we also raise the possibility that interaction of Li+ with anionic membrane phospholipids could play a role in its pharmacological action.

The structural organization of free and esterified cholesterol in human high density lipoproteins has been studied by high-field 1H and 13C NMR. The measurements are consistent with free cholesterol being present in at least two different environments. Part of the free cholesterol is oriented in the outer surface layer of the high density lipoprotein particle in contact with phospholipid or apoprotein, or both. The rest is probably present in the liquid, hydrophobic core of the HDL particle.

In the presence of lanthanides both lipids have similar polar group conformations; the glycerylphosphorylcholine group is extended approximately parallel to the hydrocarbon chains. The packing of the lysolecithin molecules in the spherical micelles is different in the absence and presence of lanthanides. In the former case the staggered packing (see Fig. 5a) is energetically favored, enabling the formation of intermolecular, electrostatic, and hydrogen bonds. In the presence of lanthanide ions the packing is dominated by the interaction of the phosphodiester group with the cation producing an arrangement of the lysolecithin molecules typical for that observed in lecithin bilayers.

The equilibrium spreading pressures (πe) of a series of glycerides and phospholipids have been determined at various temperatures. Pure mono, di- and triglycerides and phosphatidylethanolamines can spread spontaneously from the crystal to form monomolecular films at the air—water interface, whereas phosphatidylcholines (lecithins) only spread from the liquid-crystal (i.e., at temperatures above the crystal or gel to liquid crystal transition temperature, Tc). Film pressures of up to 50 mN m−1 can be attained. Glycerides and phosphatidylcholines form liquid expanded monolayers in equilibrium with the bulk lipid while phosphatidylethanolamines can form both condensed and liquid expanded films. Liquid expanded monolayers are stable with respect to the bulk, lipid phase when π πe leads to collapse and formation of bulk, lipid phase without significant overcompression. Condensed monolayers of phosphatidylcholine are metastable (πe = 0 when T < Tc) and significant overcompression is observed before collapse to the gel or the monohydrate occurs. The equilibrium spreading pressures increase linearly with temperature until changes in physical state of the bulk lipid occur. On fusion or transition to a liquid crystalline state, the temperature coefficient of the equilibrium spreading pressure changes sign. The enthalpies and entropies of spreading are used to gain information on the structure of the lipid monolayers. The entropy of spreading and thus the order in the resulting monolayer is about midway between that of the crystal and the melt, depending on whether the compound spreads to a condensed or liquid expanded monolayer.