Analysis of known crystals to design polymorph prediction strategies.

Computational analysis of known crystals was used to provide insight into polymorph prediction strategies. It was hypothesized that intermolecular crystalline interactions are inadequately accounted for in current computational strategies. The QEq method of partial charge assignments was applied to the crystal milieu (CMc) and to the isolated molecule (IMc). For 90 known crystal structures, these two partial charging methods showed that the unit cell energy was almost always lower (more stable) with CMc partial charge assignments. In simulations on a model drug, the CMc charging re-ranked the unit cell energies of possible polymorphs in a way that aided the identification of physically reasonable packings more easily than IMc. Decomposing the unit cell energy for known crystals showed that the cohesive IMc deviation from CMc was dominant. On the other hand, for simulations, the corresponding IMc conformational component of unit cell energy dominates when conformational adaptive strategies (CA) are used; this was not apparent with rigid-body simulations (RB). Furthermore, evidence is presented that polymorph strategies that use unit cell energy for optimizing are especially prone to this undesired conformational bias. Suggestions are made for polymorph strategies that might enhance the probability of identifying physically relevant polymorphs in the future.

Assessment of reflection pulse wave in patients with cardiomyopathy: evaluation of noninvasive measurement of wave intensity.

OBJECTIVE: We assessed the reflection pressure wave using noninvasive measurement of wave intensity (WI) in patients with cardiomyopathy. METHODS AND RESULTS: Subjects included 8 patients with hypertrophic cardiomyopathy (HCM group) and 10 patients with dilated cardiomyopathy (DCM group). Twelve healthy subjects were used as a control group. By using a combined Doppler and echo-tracking system, changes in vascular diameter (dD) and blood flow velocity (dV) were recorded simultaneously at the common carotid artery and dD x dV was measured as WI. In the components of WI, the positive component of early systolic phase (FE) and the negative component following FE (B) were significantly reduced in the DCM group. There was a significant positive correlation between FE and B in all 3 groups. The appearance time of B was significantly shorter in the HCM group and significantly longer in the DCM group compared with the control group. CONCLUSIONS: It was suggested that the value of the reflection pressure wave was influenced by the left ventricular contractility, and that the effect of the reflection pressure wave appeared earlier in patients with HCM and later in patients with DCM compared with the control subjects.

Heart failure in 3 patients with acromegaly: echocardiographic assessment.

We evaluated 3 patients with acromegaly who developed heart failure. Heart failure appeared to be due to acromegalic cardiomyopathy in 2 patients who did not have hypertension or evidence of coronary artery disease, and it was possibly due to acromegalic cardiomyopathy combined with familiar hypertrophic cardiomyopathy in 1 patient. The common echocardiographic findings in the present three cases were: 1) enlargement of the left atrium, 2) markedly dilated left ventricular cavity with diffuse hypokinesis, 3) decrease of indices of the left ventricular systolic function, and 4) no evidence of left ventricular hypertrophy. Echocardiographic findings in acromegaly with congestive heart failure resemble those of idiopathic dilated cardiomyopathy.

Assessment of left atrial appendage function after cardioversion of atrial fibrillation: relation to left atrial mechanical function.

Although several flow patterns in the left atrial appendage have been described, mechanical determinants of its function have not been elucidated in human beings. We attempted to investigate changes in left atrial appendage function after cardioversion of atrial fibrillation and examine the potential relation between appendage function and left atrial mechanical function. Twenty patients without mitral valvular disease underwent transesophageal and transthoracic echocardiography at 24 hours and 1 week after cardioversion of atrial fibrillation. Left atrial appendage function was assessed by the pulsed Doppler measurements of left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively. Left atrial mechanical function was evaluated by the transmitral A-wave velocity, percent atrial contribution of the total left ventricular filling (percent atrial filling), and the pulmonary venous A-wave velocity. Left ventricular function was also estimated with conventional M-mode echocardiography. The late appendage emptying and filling velocities markedly increased during 1 week after cardioversion (p < 0.0001, respectively). This finding was associated with an increase in left atrial mechanical function. Changes in the late emptying and filling velocities significantly correlated with changes in the transmitral A-wave velocity (r = 0.59, p < 0.01), percent atrial filling (r = 0.61, p < 0.005), and the pulmonary venous A-wave velocity (r = 0.56, p < 0.05). In contrast, little change was observed in the early emptying and filling velocities. There was no relation between the indexes of left ventricular function and those of appendage function. In conclusion, unless there was an alteration of the loading conditions, left atrial appendage function improved over several days after cardioversion, and its function was related to left atrial mechanical function.

[Assessment of allergenic activity of heated and ovomucoid-depleted egg white].

We investigated allergenic activity of heated and ovomucoid (OM)-depleted egg white by RAST inhibition tests, skin tests and and oral challenge tests. Freeze-dried egg white, OM and ovalbumin (OA) were coupled with CNBr-activated paper discs. Freeze-dried, heated, and heated and OM-depleted egg white antigens were used as inhibitors in RAST inhibition tests. Freeze-dried egg white significantly inhibited the IgE-binding to freeze-dried egg-white-, OM- and OA-discs. Heated egg white showed a significant inhibition against only OM-disc, but heated and OM-depleted egg white didn't effectively suppress IgE-binding to all discs. Fifty-six patients were subjected for skin tests and 27 patients for oral challenge tests with freeze-dried egg white, heated egg white and heated and OM-depleted egg white. Eighteen of 25 subjects with positive prick tests results to freeze-dried egg white showed negative results to heated egg white. Four of 7 cases with positive prick test results to heated egg white gave negative results to heated and OM-depleted egg white. 20-minutes patch tests showed almost similar results to prick tests. Four of 8 subjects showing positive oral challenge tests with freeze-dried egg white were negative to heated egg white. All of 4 with positive oral challenge tests by heated egg white were negative results to heated and OM-depleted egg white. These evidence indicated that heated and OM-depleted egg white was more hypoallergenic than heated egg white.

Gender equality and sustainable human development are key issues.

PIP: In a message to the Indochina Women's Parliamentarians Meeting, Hirofumi Ando, Deputy Executive Director of the United Nations Family Planning Association (UNFPA), encouraged participants to link gender equality and development issues. Ando noted that many of the goals of the 1994 International Conference on Population and Development imply recognition of the need to redress gender inequalities and empower women. The Program of Action adopted in Cairo requires countries to achieve universal access to primary education and reproductive health care services. Parliamentarians in attendance were urged to mobilize the financial resources and political will necessary to implement programs in these areas.^ieng

Assessment of preload reserve in myocardial ischemia--the relation between preload reserve and ischemic size differs between anterior descending and circumflex coronary artery occlusions in a canine model.

The role of changes in preload in maintaining stable hemodynamics during coronary obstruction was assessed in the presence of myocardial ischemia due to occlusions of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. Changes in preload (mean left atrial pressure) to maintain a constant stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed sonomicrometrically. Ventricular function curves relating left atrial pressure to stroke volume were assessed during a control state and after 1 min of coronary occlusion. The extent of preload reserve after coronary occlusion was examined on the ventricular function curves and was defined as the change in mean left atrial pressure required to maintain stroke volume at the level of the control state under conditions of regional ischemia. Ischemic size was determined by a stereo-angiogram after the animals were sacrificed. The extent of preload reserve (X) was linearly related to the ischemic size (Y) in both LAD (Y = 0.90 + 0.16X, r = 0.76, p < 0.001) and LCX (Y = -1.79 + 0.19X, r = 0.79, p < 0.001) occlusions. The slopes of the regression lines in LAD and LCX occlusions were the same. The X intercepts of these lines were -5.6% and 9.4% of the left ventricular weight in LAD and LCX ischemia (p < 0.001), respectively. Thus, the presence of systolic wall motion abnormalities due to coronary occlusion can be compensated for hemodynamically by changes in the preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)