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Biomedical subjects

A Singhal

Publications and source records attributed to A Singhal.

At least 91 records · Page 5Linked to original sources

Drug targeting in Leishmania donovani infections using tuftsin-bearing liposomes as drug vehicles.

The efficacy of sodium stibogluconate against Leishmania donovani infections was markedly enhanced by encapsulating this drug in tuftsin-bearing liposomes. Also, pretreatment of the animals with these liposomes (free of drug) rendered them resistant to this infection, possibly by activating the host's macrophages. These results demonstrate that tuftsin-bearing liposomes besides delivering the drug to the target cells could also enhance the nonspecific resistance against infections, thus offering an additional advantage over the use of tuftsin-free liposomes as drug carriers in leishmania therapy.

Adjuvants, Immunologic↗

Antibody-mediated targeting of differentiation inducers to tumor cells: inhibition of colonic cancer cell growth in vitro and in vivo. A preliminary note.

A differentiation inducer (sodium butyrate) encapsulated in liposomes that are in turn covalently linked to anti-Lex monoclonal antibody, SH1 (IgG3 isotype), was successfully targeted to human colonic adenocarcinoma HRT-18 and HT29 cells expressing Lex antigen in vitro as well as in vivo in athymic nu/nu mice. Tumor cell growth was significantly inhibited and was associated with changes in cell morphology and increases in membrane-bound alkaline phosphatase and gamma-glutamyltranspeptidase, indicating the occurrence of butyrate-induced differentiation.

Adenocarcinoma↗

Serum haloperidol concentration and choreiform movements in Huntington's disease.

The relationship between serum haloperidol concentration and improvement in abnormal movements was investigated in 20 adult Huntington's disease (HD) patients. Serum samples and assessments of severity of chorea were simultaneously obtained from each patient. Data were obtained prior to and at one or more doses following the initiation of haloperidol in ten patients. Serum was analyzed for haloperidol by two different methods, gas chromatographic/mass spectrometric (GC/MS) and radioreceptor (RR) assays. Steady-state serum haloperidol concentrations (GC/MS) of 0.5 to 24 ng/ml were observed following administration of doses of 1 to 40 mg/d and varied markedly between patients. Only results from the GC/MS assay were used for examining relationships with dose and clinical response because of insensitivity of RR assay. Significant improvement of abnormal movements, greater than 30% from baseline, occurred at serum concentrations between 2 and 5 ng/ml, which corresponded to doses of 1.5 to 10 mg/d. Further improvement in abnormal movements at serum concentrations above this range was minimal.

Adult↗

Functional drug targeting to erythrocytes in vivo using antibody bearing liposomes as drug vehicles.

Covalent attachment of anti-erythrocyte F(ab')2 to the liposome surface has recently been shown to considerably enhance the liposome binding to erythrocytes in vivo. These antibody bearing liposomes have now been found quite effective as vehicles for delivering the antimalarial drug, chloroquine, to erythrocytes in Plasmodium berghei-infected mice. This demonstrates the usefulness of antibody targeted liposomes as carriers for site-specific drug delivery.

Animals↗

Antibody-mediated targeting of liposomes to red cells in vivo.

Covalent attachment of anti-rat erythrocyte F(ab')2 to liposomes specifically enhanced their binding to rat erythrocytes in vivo and reduced their uptake by the liver. Furthermore, at least 20-30% of the cell-bound liposomes delivered their contents to the cells. Besides, the liposome binding did not affect the survival time of the target cells at least up to 3 h in the blood circulation. These results demonstrate for the first time that liposomes can be successfully targeted to cells other than liver cells in vivo.

Adsorption↗

Antibody-mediated targeting of liposomes to erythrocytes in whole blood.

F(ab')2 fragments derived from anti-rat erythrocyte antibody or normal rabbit serum IgG were covalently attached to the surface of liposomes consisting of equimolar amounts of egg phosphatidylcholine and cholesterol. These liposomes were interacted with rat, monkey or mouse blood, and their binding to both red and white blood cells was determined. Results of these studies show that coupling of liposomes to anti-rat erythrocyte F(ab')2 considerably enhances their binding to erythrocytes in rat blood. However, no such increase in the binding was observed with rat leukocytes or monkey and mouse erythrocytes. Besides, the interactions between the liposomes and target cells did not affect the permeability properties of the liposome bilayer. These observations indicate that liposomes coupled to cell-specific antibodies may serve as highly useful carriers for homing of drugs/enzymes to specific cells in biophase.

Animals↗

New index of cardiac contractility during stress testing with treadmill.

Experimental demonstration that the external phonocardiogram is similar to the third derivative (rate of acceleration) of LV pressure, and that catecholamines cause a similar increase of the early systolic wave of the first derivative of LV pressure and of S1 prompted a study of the first sound during stress testing. Following a previous study with different types of ergometers, the present investigation was based on records of 10 normal, young volunteers, taken during treadmill exercise while a phonocardiogram was recorded at the apex. The first heart sound increased in all of them averaging an eightfold increase during maximal stress. Comparison of the changes in amplitude of S1 with changes of heart rate, blood pressure, and cardiac output revealed that the first showed the most constant proportional increase while sometimes one or the other parameter showed only a moderate change. The possible causes of this apparent lack of reaction is discussed. The importance of the first sound as an index of contractility is stressed, and the suggestion of a routine study of this index in cardiac patients submitted to stress tests is advanced.

Adult↗

Noninvasive index of cardiac contractility during stress testing: a collaborative study.

The present study was conducted in parallel in three different institutions with a similar purpose but using different technical setups. Based on the experimental demonstration that the external phonocardiogram is similar to the rate of acceleration (d3P/d3t) of the left ventricular pressure, and that catecholamines in a similar way increase the early positive wave of the left ventricular pressure and the first heart sound (S1) of the external phonocardiogram; knowing that exercise causes secretion of catecholamines and sympathetic reflexes, we have studied the S1 changes as a result of exertion in 34 normal young subjects. Blood pressure, heart rate, electrocardiograph, and phonocardiograph recordings of each subject were taken. In 10 subjects, cardiac output was also recorded by impedance cardiography. The result of the study was that the first heart sound increased routinely 4-5 times the normal amplitude; in a few subjects the increase was up to 15 times greater. While the extent of increase of S1 was proportional to the severity and duration of the effort and was usually proportional to the increase of other parameters, exceptions were noted as having marked increase of S1 with moderate increase of either blood pressure or heart rate. This was explained by the different receptors activated by the catecholamines and by the complexity of hormonal and neural influences acting on various organs in a stress test. The amplitude of S1 was found to be a reasonably reliable index for following changes of cardiac contractility during exercise, and the suggestion was made that this parameter should be studied in parallel with the others in routine stress tests.

Adolescent↗

Assessment of left ventricular function by noninvasive methods.

The possibility of evaluating left ventricular function by noninvasive methods is discussed in detail. The methods that are considered are electrocardiograph, phonocardiography, apex cardiography, sphygmography, impedance cardiography, electrokymography, and echocardiography. Following a brief section of 'definitions', each method is described in detail including technical problems, difficulties, and results. The systolic time intervals and the stress tests are briefly discussed. Based on modern experimental studies, the stress test should include both an electro- and a phonocardiogram. In the latter, one would measure the amplitude of the first heart sound as an index of contractility. The conclusion is that combined methods give the best results. They are electrocardiography, phonocardiography, impedance cardiography, and echocardiography. An alternative, dictated by technical problems, is to use at first phonocardiography and impedance plus electrocardiography; then echocardiography plus electrocardiography; and then, if indicated, a stress test might complete the study; the latter should include both an electrocardiogram and a phonocardiogram.

Adult↗

Various types of systolic clicks in patients with muscular subaortic stenosis.

Four clinical cases of subaortic hypertrophic muscular stenosis are discussed. All four, in addition to a loud systolic murmur, had a loud systolic click. However, the timing of the click and its relationship to the phase of the carotid pulse were different in each case varying from close to medium and to distant (or midsystolic). The comparison of the sound tracing with the carotid tracing demonstrated that, in each case, a sudden change in acceleration was taking place. In one, the click coincided with the onset of the carotid upstroke; in another, with the first peak of the carotid pulse; in the third, with the trough between first and second peak of the pulse; in the last, with a sudden drop of the pulse at mid-systole caused by sudden obstruction to flow. It is concluded that the clicks were caused by rapid changes of acceleration resulting from the abnormal aortic ejection. Thus, the study of the carotid pulse and of the sound tracing are important for a non-invasive diagnosis together with the echo study of the septum and ventricular wall.

Adolescent↗

Specific interactions of liposomes with PMN leukocytes upon incorporating tuftsin in their bilayers.

Incorporation of tuftsin derivatives, Thr-Lys-Pro-Arg-NH-C18H37 or Thr-Lys-Pro-Arg-NH-(CH2)2-NH-COC15H31, into an egg phosphatidylcholine/cholesterol liposome bilayer led to significantly enhanced binding of the liposomes to PMN leukocytes at 37 degrees C but not at 0 degree C. Under identical conditions, no such enhanced binding of the liposomes was observed with erythrocytes and lymphocytes. These results demonstrate that grafting of tuftsin on the liposome bilayer enables the liposome to recognize specifically the PMN leukocytes and to deliver its contents to these cells.

Cholesterol↗

Diagnosis of tricuspid insufficiency by non invasive methods.

The diagnosis of tricuspid insufficiency was first made at the end of last century, based on clinical signs. Graphic tracings of the venous system were soon recorded and were demonstrated useful in the forties and fifties. New methods involving invasive procedure or expensive instrumentation have been described in the last twenty years. The present study was made in order to re-examine the value of the non-invasive, graphic methods, which would assure a simple and inexpensive study for these patients.

Adolescent↗

The jugular and hepatic tracings in normal subjects and in conduction defects.

The present study is a revision of the patterns of the jugular and hepatic tracings, two non-invasive tracings of the venous system. The study was performed in 40 subjects; 30 of them were normal while 10 had minor conditions affecting the left heart. The time of onset and peak of the various waves was statistically evaluated in this series. In addition, 14 cases of bundle branch block and 10 cases of grade 2 or 3 atrioventricular block were studied in order to better determine the cause of certain waves. Among the findings are: 1) the presence of a double A wave in 5 normals and in over one-half of the patients with AV block; 2) the frequent occurrence of a double C wave (an occurrence that required the labeling of the two peaks as t and C both in normal subjects and in clinical cases); 3) the possibility of either a double V wave or a small V wave, followed by a large H wave, especially in hepatic tracings. The mechanism of the various waves is discussed and the possible transmission of left-sided mechanical events to the right atrium and the venous system is postulated.

Adolescent↗