Fast method for 1D non-cartesian parallel imaging using GRAPPA.

MRI with non-Cartesian sampling schemes can offer inherent advantages. Radial acquisitions are known to be very robust, even in the case of vast undersampling. This is also true for 1D non-Cartesian MRI, in which the center of k-space is oversampled or at least sampled at the Nyquist rate. There are two main reasons for the more relaxed foldover artifact behavior: First, due to the oversampling of the center, high-energy foldover artifacts originating from the center of k-space are avoided. Second, due to the non-equidistant sampling of k-space, the corresponding field of view (FOV) is no longer well defined. As a result, foldover artifacts are blurred over a broad range and appear less severe. The more relaxed foldover artifact behavior and the densely sampled central k-space make trajectories of this type an ideal complement to autocalibrated parallel MRI (pMRI) techniques, such as generalized autocalibrating partially parallel acquisitions (GRAPPA). Although pMRI can benefit from non-Cartesian trajectories, this combination has not yet entered routine clinical use. One of the main reasons for this is the need for long reconstruction times due to the complex calculations necessary for non-Cartesian pMRI. In this work it is shown that one can significantly reduce the complexity of the calculations by exploiting a few specific properties of k-space-based pMRI.     

Drug analysis with polarographic methods. 33. Electroanalytic studies of a new benzodiazepine: [6(o-chlorophenyl)-2,4-dihydro-2-[(4-methyl-1-piperazinyl) methylene]-8-nitro-1H-imidazol[1,2-a][1,4]benzodiazepine-1-one (WHO) (loprazolam,1)] and content determination its drug forms

Loprazolam (1) is a tricyclic benzodiazepine containing a new butazadiene moiety, which has not been investigated by polarography up to now. 1 is reduced in three waves at a DME over the whole pH-region. In BRP (pH 2-9) 10 electrons are consumed in this process. The first step is suitable for the determination of 1 in Loprazolam tablets containing 1 or 2 mg. These tablets are on the pharmaceutical market in several European countries. The mechanism of the electrode process will be reported in the communication XXXIV.     

Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action

Summary The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1 – 3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals died following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC₅₀ 2.1 ±0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 g/kg i.v.), phenylephrine (8 g/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca²⁺ channels.Send offprint requests to A. K. Mir at the above address     

Conductance properties and voltage dependence of an anion channel in amphibian skeletal muscle

Single anion-selective channels were studied in excised membrane patches of adult frog toe muscle. The conductance and the probabilityp _o of the main open state were determined for various ionic compositions of the extra-and intracellular solutions. =280 pS in symmetrical 110 mM NaCl, pH 7.4 solutions at 15°C. Higher values were found at elevated internal or external NaCl concentrations, in 70 mM external CaCl₂ and at lower extracellular pH. Thep _o(E) curve declined steeply with hyperpolarization and was shifted towards more negative potentials at increased internal ionic strength and at higher external pH. Positive shifts were induced by extracellular Ca. The results show that the anion channel saturates at Cl concentrations >110 mM, that the potential profile of an open channel is almost symmetrical and that channel gating is affected by neighboring channels. It is suggested that the anion channel has a voltage sensor (effective gating charge 4.3) and a similar collection of local fixed charges on the extra- and intracellular sides as voltage-gated cation channels.     

Diminished neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in patients after treatment with chemotherapy or hematopoietic cell transplantation

Relapse is the most common cause of treatment failure for advanced cancer, even those treated with autologous hematopoietic cell transplantation (HCT). Effective tumor-specific immunotherapy may decrease relapse, however, this will fail if the immune system is unable to respond. We developed a strategy to test immune responses with a single injection of the bona fide neo-antigen KLH. The model was first tested in 37 normal volunteers using three KLH vaccines: Intracel KLH, Biosyn KLH, and Biosyn KLH + adjuvant. Despite finding the immunogenic epitope conserved in both products, intact Intracel KLH induced a better response compared to a purified 350/390 kDA subunit of KLH contained in the Biosyn KLH product. Addition of a synthetic oil adjuvant (Montanide ISA51) restored the response to a single injection of Biosyn KLH. A quantitative readout measured by a KLH-specific cellular and humoral response with isotype switching 1 month after KLH vaccination was established. To test the integrity of the adaptive immune response in cancer patients, we vaccinated 14 patients post-HCT and 19 patients with advanced cancer with KLH vaccines that elicited a 100% response rate in normal volunteers. In marked contrast to normal subjects, both responses were significantly impaired up to 16 months after autologous HCT with an intermediate response in advanced cancer patients. KLH vaccines are safe and require only a single injection to test neo-antigen responses providing an optimal platform for definitive testing of strategies to improve diminished immune recovery after chemotherapy or post-HCT.     

Improved immunoglobulin production in dialysis patients treated with recombinant erythropoietin.

Improvements in B lymphocyte function have been reported in hemodialysis patients receiving erythropoietin. The present investigation studied whether erythropoietin interferes with B cell function and the mechanisms of this effect. Antibody production by cultured peripheral blood mononuclear cells (PBMC) (7 days) from 15 dialysis patients before and during erythropoietin treatment and from 14 healthy controls was followed. IgG and IgA were formed less in the uremic group than in healthy subjects. After 8 weeks of erythropoietin (hematocrit rose from 19 to 31%) basal IgG formation by PBMC rose from 304 +/- 83 to 566 +/- 49 ng/ml (p less than 0.02), while IgA production rose from 380 +/- 121 to 563 +/- 362 ng/ml (p less than 0.01). IgM production, which appeared to be normal in uremia, remained unchanged during erythropoietin treatment. Production of IgG and IgA stimulated by pokeweed-mitogen was subnormal in uremia, but improved under erythropoietin therapy. To establish whether erythropoietin acted by itself or through correction of the renal anemia, healthy PBMC were directly incubated with 2 U/ml of erythropoietin. Under these conditions production of IgG (+19%), IgA (+28%), and IgM (+32%) was enhanced. Taken together these data indicate a direct stimulant effect of erythropoietin on B lymphocytes in end-stage renal failure.     

Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man

Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect of splenic exposure (2.0 mW/m², 3.5 MHz, 5 minutes) to ultrasound on the immune response to Rubella vaccination in 41 anti-Rubella antibody-negative volunteers. The measured parameters (blood cell count, IgA, IgM, IgG including subclasses IgG1-IgG4, isoagglutinins, anti-Rubella hemagglutinin and hemolysin titers, complement C3, skin tests to mumps and tuberculin, T, B and O lymphocytes, esterase-positive and negative T-cell subsets) suggest changes dependent on the time of vaccination, but provide no evidence of an immunosuppressive effect of ultrasound in man.     

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.