Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.     

Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 microns average microbubble size, concentration 8 x 8(8)/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial blood flow changes and showed a significant correlation with radiolabeled microspheres (r = 0.65, p = 0.0001).     

Association of plasma renin activity and echocardiographic left ventricular hypertrophy with frequency of new coronary events and new atherothrombotic brain infarction in older persons with systemic hypertension

In older hypertensive persons, male gender, prior coronary artery disease, prior atherothrombotic brain infarction (ABI), and echocardiographic left ventricular (LV) hypertrophy are independent risk factors for new coronary events; age, prior ABI, and echocardiographic LV hypertrophy are independent risk factors for new ABI. The data suggest that high plasma renin activity in hypertensive older persons is associated with a high risk of new coronary events and of new ABI through its association with echocardiographic LV hypertrophy.     

Parsalmide: a new anti-inflammatory agent. III. Study of the analgesic and anti-inflammatory activity

When human chorionic gonadotropin (hCG) was treated with a 20-fold molar excess of N-acetylimidazole in aqueous solution, two tyrosyls were acetylated, resulting in a 50% reduction in in vivo biological activity. With increased quantities of reagent, the number of tyrosyls acetylated increased but with no further decrease in the biological activity. In vitro biological activity (binding to hCG receptors) of the hormone was not affected at all. Acetylation in urea increased tyrosyl modification, accompanied by acetylation of some lysyls, yielding a product in which all seven tyrosyls were acetylated and both in vivo and in in vitro biological activities were completely abolished. Deacylation with hydroxylamine partially restored biological activity of some but not all of the modified products. When individual hCG subunits were treated with the same reagent, the number of tyrosyls acetylated in each subunit again increased with increasing amounts of reagent, up to three in the alpha subunit and two in the beta subunit in the absence of urea. The tyrosyls in the beta subunit appeared less reactive to the reagent than those in the alpha subunit. Subunits modified to these extents retained ability to recombine as examined by gel electrophoresis, but the recombined products varied considerably in both in vivo and in vitro biological activities. A completely tyrosyl-acetylated product of hCG-alpha did not combine with intact hCG-beta, while fully modified hCG-beta did with intact hCG-alpha.     

Paraplane analysis from precordial three-dimensional echocardiographic data sets for rapid and accurate quantification of left ventricular volume and function: a comparison with magnetic resonance imaging

OBJECTIVES: Three-dimensional echocardiography (3DE) calculates left ventricular volumes (LVV) and ejection fraction (EF) without geometric assumptions, but prolonged analysis time limits its routine use. This study was designed to validate a modified 3DE method for rapid and accurate LVV and EF calculation compared with magnetic resonance imaging (MRI). METHODS: Forty subjects included 15 normal volunteers (group A) and 25 patients with segmental wall motion abnormalities and global hypokinesis caused by ischemic heart disease (group B) who underwent 3DE with precordial rotational acquisition technique (2-degree interval with electrocardiographic and respiratory gating) and MRI at 0.5 T, electrocardiogram (ECG)-triggered multislice multiphase T1-weighted fast field echo. End-diastolic and end-systolic LVV and EF were calculated from both techniques with Simpson's rule by manual endocardial tracing of equidistant parallel left ventricular short-axis slices. Slicing from the 3DE data sets were done by both 2.9-mm slice thickness (method 3DE-A) and by 8 equidistant short-axis slices (method 3DE-B); for MRI analysis, 9-mm slice thickness was used. RESULTS: Analysis time required for manual endocardial tracing of end-diastolic and end-systolic short-axis slices was 10 minutes for the 3DE-B method compared with 40 minutes by the 3DE-A method. For all 40 subjects the mean +/- SD of end-diastolic LVV (mL) were 181 +/- 76, 179 +/- 73, and 182 +/- 76; for end-systolic LVV (mL), 120 +/- 76, 120 +/- 75, and 122 +/- 77; and for EF (%), 39 +/- 18, 38 +/- 18, and 38 +/- 18 for MRI, 3DE-A, and 3DE-B methods, respectively. The differences between 3DE-A and 3DE-B with MRI for calculating end-diastolic and end-systolic LVV and EF were not significant for the whole group of subjects as well as for the subgroups. The 3DE-B method had excellent correlation and close limits of agreement with MRI for calculating end-diastolic and end-systolic LVV and EF: r = 0.98 (-1.3 +/- 26.6), 0.99 (-1.6 +/- 21. 2), and 0.99 (0.2 +/- 5.2), respectively. The correlation between 3DE-A and MRI were r = 0.97, 0.98, and 0.98, and the limits of agreement were -1.4 +/- 36, -0.6 +/- 26, and 0.6 +/- 8 for calculating end-diastolic and end-systolic LVV and EF, respectively. In addition, excellent correlation and close limits of agreement between 3DE-A and 3DE-B with MRI for LVV and EF calculation was also found for the subgroups. Intraobserver and interobserver variability (SEE) of MRI for calculating end-diastolic and end-systolic LVV and EF were 6.3, 4.7, and 2.1; and 13.6, 11.5, and 4.7; respectively, whereas that for 3DE-B were 3.1, 4.4, and 2.2; and 6.2, 3.8, and 3. 6; respectively. Comparable observer variability was also found for the A and B subgroups. CONCLUSIONS: The 3DE-A and 3DE-B methods have excellent correlation and close limits of agreement with MRI for calculating LVV and EF in both normal subjects and cardiac patients. The 3DE-B method by paraplane analysis with 8 equidistant short-axis slices has observer variability similar to MRI and reduces the 3DE analysis time to 10 minutes, therefore offering a rapid, reproducible, and accurate method for LVV and EF calculation.     

Functional and bioenergetic consequences of postinfarction left ventricular remodeling in a new porcine model. MRI and 31 P-MRS study

BACKGROUND: The underlying mechanisms by which left ventricular remodeling (LVR) leads to congestive heart failure (CHF) are unclear. This study examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal model. METHODS AND RESULTS: Remodeling was induced by circumflex coronary artery ligation in young pigs. LV mass, volume, ejection fraction (EF), the ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simultaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized 31P-nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during pyruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coronary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 normal animals. EF decreased from 55.9 +/- 5.6% in normals to 34.6 +/- 2.3% in the LVR group (P < .05) and 24.2 +/- 2.8% in the CHF group (P < .05 versus LVR). The infarct scar was larger in CHF hearts than in LVR hearts (P < .05). In normals, LV myocardial creatine phosphate (CP)/ATP ratios were 2.10 +/- 0.10, 2.06 +/- 0.16, and 1.92 +/- 0.12 in subepicardium (EPI), mid myocardium (MID), and subendocardium (ENDO), respectively. In LVR hearts, the corresponding ratios were decreased to 1.99 +/- 0.13, 1.80 +/- 0.14, and 1.57 +/- 0.15 (ENDO P < .05 versus normal). In CHF hearts, CP/ATP ratios were 1.41 +/- 0.14, 1.33 +/- 0.15, and 1.25 +/- 0.15; (P < .05 versus LVR in EPI and MID). The calculated myocardial free ADP levels were significantly increased only in CHF hearts. CONCLUSIONS: Bioenergetic abnormalities in remodeled myocardium are related to the severity of LV dysfunction, which, in turn, is dependent on the severity of the initiating myocardial infarction.     

Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this Multicenter Study

Reproductive aging in women is closely tied to the loss of ovarian follicles through atresia. The sentinel endocrinologic finding is the monotropic FSH rise, associated with a decline in ovarian inhibin B secretion. Fertility becomes significantly compromised long before overt clinical signs occur, such as cycle irregularity. Compromised fertility is primarily related to oocyte dysfunction. As women with regular cycles near the end of the reproductive years, the following changes are usually manifested: 1) the selection and development of a dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a short follicular phase and total cycle length; and 4) ovarian steroid secretion is normal. The relationships, if any, between the monotropic FSH rise, accelerated follicular atresia, shortened follicular phase, and oocyte quality remain to be determined. The next phase of reproductive aging is the perimenopause. Lack of predictability is the rule with regard to the nature and duration of the perimenopause. Long cycles are interspersed with short ones, and intermittent ovulatory cycles are intermingled with periods that are hormonally indistinct from the postmenopausal state. Even after the last menstrual period, evidence of intermittent ovarian estradiol production may still be detected. Although fertility is severely compromised during the perimenopause, ovulation may occur without warning and contraception must be practiced if pregnancy is not desired. Further studies are needed to elucidate the factors contributing to oocyte abnormalities in women of advanced reproductive age, as well as the factors that determine the rate of follicle atresia and the length of the reproductive life span.     

Biotransformation of 10-(3-quinuclidinylmethyl)phenothiazine (LM 209), a new anti-allergy agent and the distribution and excretion of its metabolites

1. Metabolism of 10-(3-quinuclidinylmethyl)phenothiazine and the distribution and excretion of the metabolites, especially the sulphoxides, were studied in rat and dog after oral and intravenous administration. 2. Urine and bile contained relatively little unchanged drug. The sulphoxide, sulphone, N-oxide and N-oxide sulphoxide derivatives were identified as well as glucuronide and sulphate conjugates, suggesting the formation of hydroxylated products. Faeces contained mainly unchanged drug but also some sulphoxide and N-oxide. In the lung, brain and cerebro spinal fluid only unchanged drug and traces of sulphoxide were found, whereas in liver sulphone and N-oxide were also present. 3. After administration of the 35S-labelled sulphoxide, the distribution of radio-activity was very different from that observed with LM 209. The biological half-life (t0-5) of SM 209 was 3 to 4 times higher than that of the sulphoxide. LM 209 is better absorbed and its diffusion in the organism is superior. 4. Metabolism of LM 209 by liver microsome preparation was more rapid than metabolism of the sulphoxide. 5. These findings indicate that the activity of LM 209 is due more to the molecule itself than to its major metabolite.     

In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mold pathogens

The in vitro activity of voriconazole was compared with that of itraconazole. Eighty-six isolates of pathogenic molds belonging to 23 species were tested by an agar dilution method in High Resolution medium. Voriconazole was more active than itraconazole against a number of hyaline molds, including several Fusarium spp. and Scedosporium prolificans. Voriconazole and itraconazole showed comparable good activity against several hyaline molds, including Penicillium marneffei and Scedosporium apiospermum, and a number of dematiaceous molds, including Bipolaris australiensis, Cladophialophora bantiana, several Exophiala spp., and several Fonsecaea spp. Our results suggest that voriconazole could be effective against a wide range of mold infections in humans.     

Interactions of a bicyclic analog of colchicine with beta-tubulin isoforms alphabeta(II), alphabeta(III) and alphabeta(IV)

In this study we have investigated the occurrence of cytochrome P450 isoforms and of related cytochrome P450 reductase in human hepatic stellate cells (hHSC), a type of cell having relevant roles in physiopathological conditions of the liver. By performing immunoblotting of hHSC microsomes and immunofluorescence analysis associated to confocal laser microscopy we detected only P450 enzymes belonging to the cytochrome P450 3A subfamily (CYP3A) as well as cytochrome P450 reductase. The presence of CYP3A was further indicated by detection of testosterone 6beta-hydroxylase activity in hHSC microsomes. Other important human P450 forms were either undetectable (CYP1A2, CYP2E1, CYP2C8/9/19 and CYP4A) or bearly detectable (CYP1A1) in hHSC. This is the first study showing existence of active cytochrome P450 isoforms in human HSC.     

Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer

PURPOSE: We study toxicity and efficacy of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or high risk superficial bladder cancer compared to the use of intravesical mitomycin C alone. MATERIALS AND METHODS: Patients with intermediate and high risk papillary superficial bladder cancer and carcinoma in situ were randomized after transurethral resection between 4 weekly instillations with 40 mg. mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or 10 weekly instillations with mitomycin C (group 2, 92 patients). RESULTS: The frequency of bacterial and chemical cystitis, and other local side effects was similar in both groups. Allergic reactions, including skin rash, were more frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p = 0.08), and other systemic side effects were more frequent in the sequential group (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of 92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70) were similar in both groups. CONCLUSIONS: We did not find any major differences in toxicity or treatment efficacy with intravesical mitomycin C and the sequential use of BCG or mitomycin C for intermediate and high risk superficial papillary bladder cancer.     

Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphonacetyl)-L-aspartate in patients with advanced colorectal cancer. Results of a phase II study

Methotrexate (MTX) and N-phosphonacetyl-L-aspartate acid (PALA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU). A phase II study was initiated to evaluate the feasibility, toxicity and efficacy of PALA/MTX and 5-FU in patients with metastatic colorectal cancer. 26 patients received PALA 250 mg/m2 as an intravenous 15-min infusion plus MTX 200 mg/m2 as a 30-min intravenous (i.v.) infusion on day 1 and 5-FU 600 mg/m2 as i.v. push on day 2. Cycles were repeated every 14 days and the 5-FU dose was escalated in the individual patient in steps of 100 mg/m2 for the third, fifth and seventh cycle in the absence of toxicity. 7 patients had received prior 5-FU-based chemotherapy while 19 patients were chemotherapy naive. Objective responses occurred in 23% of patients (1 CR, 5 PR of which 2 were pretreated), no change in 13 patients (50%) and tumour progression (6 patients) or toxic death (one patient) in 27%. Responses lasted for a median of 7 months (range 6-9), the median time to progression was 4 months and median survival 13 months. Toxicity was mainly gastrointestinal with diarrhoea and mucositis, and severe or life threatening in only 3 patients. In 3 patients an increase in serum glucose levels occurred while being treated with PALA/MTX and 5-FU. 2 patients with insulin-dependent diabetes had a 33% increase in insulin requirement and 1 patient with dietary-controlled diabetes died due to a ketoacidotic coma. PALA/MTX/5-FU in this dose and schedule is active in patients with colorectal cancer. Hyperglycaemia may be a potential side-effect of PALA-containing regimens especially in patients with diabetes. Careful monitoring of serum glucose levels in these patients is indicated.     

Metals extraction with carboxylic acids. II. Effect of temperature on the extraction of Cu,Ni, Co(II), Zn,Fe(III) and Co(III)

The relation between the extraction temperature and the coefficient of distribution of various metals between aqueous phases and kerosene solutions of Versatic acid has been investigated.Using a mathematical procedure, it was established that with increasing temperature the distribution coefficient changes if the composition of the metal-Versatic complex is temperature-dependent. In the case of trivalent iron a reversible increase in distribution coefficient occurs when the temperature is raised. It is suggested that this is due to a reversible depolymerization of the complex. The distribution coefficient of trivalent cobalt also increases with temperature, but here the increase is irreversible, possibly because the number of covalently bound carboxylate groups changes.In general, the distribution coefficient of metals which do not show variations in the composition of their complexes with Versatic, such as Cu, Ni, Co(II) and Zn, does not change appreciably with temperature.     

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.     

DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), a new noradrenaline neurotoxin, and stimulus conditions affecting acquisition of two-way active avoidance.

Several CS and UCS variables known to affect the rate of acquisition of the 2-way active avoidance task were investigated in rats treated with the novel selective noradrenaline neurotoxin DSP4 (50 mg/kg, ip). 234 male Sprague-Dawley rats were used in 6 experiments. Although the DSP4 Ss did not demonstrate the linear relation between CS duration and avoidance acquisition to the same extent as controls, their avoidance performance was as drastically disrupted as that of the controls both by preexposure to the CS and by increasing levels of shock intensity. DSP4 Ss also evidenced fear retention for the shuttle box cues previously associated with inescapable shocks to as marked a degree as control Ss. Biochemical data indicated profound noradrenaline depletion in the cortex and hippocampus and a lesser depletion in the hypothalamus. Findings offer a behavioral characterization of the consistent DSP4-induced impairment of 2-way active avoidance acquisition. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comment on: A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the the Danish Head and Neck Cancer Study (DAHNCA) Protocol 5-85

Colonic adenocarcinoma was diagnosed by surgical biopsy in a domestically raised 3-yr-old male corn snake (Elaphe guttata guttata). The snake presented with a history of constipation. Several masses were palpated in the distal coelomic cavity. On proctoscopy, a nodular firm white mass encircled the distal colon proximal to the cloaca. The histologic diagnosis was transmural mucinous colonic adenocarcinoma with scirrhous reaction. Resection of the affected region alleviated intestinal obstruction for at least 4 mo, after which the snake was lost to follow-up.     

Use of maintenance intravesical bacillus Calmette-Guérin (BCG), with or without intradermal BCG, in patients with recurrent superficial bladder cancer. Long-term follow-up of a randomized phase 2 study

Current suicide statistics only represent a portion of suicides committed by the elderly. Indirect self-destructive behaviors (ISDBs) cause many more deaths than direct methods yet they often are ignored, misinterpreted, or unidentified. Medical noncompliance is identified as a form of ISDB, leading to diminished quality of life and an expedited death. While noncompliance occurs for a variety of reasons, it is a form of self-destruction for a portion of the elderly population. The nurse practitioner is in a unique role to identify ISDBs, as well as risk factors for developing these behaviors, and to construct methods for intervening and supporting those who wish to continue life.     

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.     

Characterization,crystal structure and luminescence properties of a new europium（Ⅲ） complex with macrocyclic ligand derived from 2,6-diformyl-4-methylphenol and diethylenetriamine

The title compound （13,27-dimethyl-3,6,9,17,20,23-hexaazatricyclo-[23.3.1.1^11,15]-triaconta-1 （29）,2,9,11,13,15（30）, 16,23,25,27- decaene-29,30-diol-N^3, N^6, N^9, O^29, O^30）-bis （nitrato-O,O＇）-europium （Ⅲ） nitrate hydrate （[EuL（NO3）2]（NO3）·H2O, L denotes the macrocyclic ligand） was prepared and characterized by elemental analysis, infrared spectra, and electrospray mass spectra. Its crystal and molecular structure was determined by X-ray diffraction. The crystal crystallized in the monoclinic system, space group C2/c with a=2.3757 （4） nm, b=1.4302（3） nm, c=1.9584（3） nm, β=91.654（5）°, M=818.60, V=6.651（2） nm^3, Z=8, D=1.635 g/cm, F（000）=3312, R=0.0542, wR=0.1045. The central ion Eu^3＋ was nine-coordinated in the coordinaton geometry of a distorted tricapped trigonal prism. The macrocycle was coordinated through two oxygen and three nitrogen atoms. Two nitrate are chelate in the opposite positions of the macrocycle, the third nitrate being ionic. At room temperature, excitation of the title complex gave rise to the characteristic emissions of the Eu^3＋ ion.     

Studies on new process procedures in plasma fractionation and industrial scale. III. Removal of precipitates by filtration through a horizontal leaf filter with centrifugal cleaning (Funda filter) as an alternative to tubular-bowl centrifuges

To study the eyes' role in maintaining the circadian rhythm in pituitary-adrenal function, 24-h patterns of corticosterone levels were compared in intact and blinded adult female rats. Rats were blinded by optic enucleation at approximately 80 days of age. Nonstress plasma corticosterone levels were determined fluorometrically in serial blood samples obtained from a tail vein at 4-h intervals for 44-h periods, 3 and 10 weeks after surgery. At 3 weeks after surgery, blinded and intact rats demonstrated comparable rhythms in corticosterone levels. At 10 weeks, steroid fluctuations in individual blinded rats still had an approximate 24-h periodicity. However, these fluctuations were no longer synchronized with the light-dark cycle or with those of other rats. These findings suggest that rats blinded as adults have a free-running pituitary-adrenal circadian rhythm.