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Biomedical subjects

C Larsen

Publications and source records attributed to C Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Early treatment with nasal continuous positive airway pressure in very low-birth-weight infants.

During 1988 and 1989, a regional cohort of 81 infants with birth weights less than 1501 g were treated with oxygen only (n = 11), early continuous positive airway pressure (CPAP) (n = 68) or mechanical ventilation from birth (n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only 4 survivors (6%) developed prognostically significant bleedings grade 2-4. No survivors had bronchopulmonary dysplasia. Follow-up at 12-39 months of age revealed definite disabilities in 6 (10%) and suspected disabilities in 2 of 62 long-term survivors. The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO2 may be effective and lenient in most infants more than 25 weeks' gestation.

Cerebral Hemorrhage↗
PubMed1992

HIV infection at outcome of pregnancy in the Paris area, France.

The prevalence of HIV infection in women at end of pregnancy, irrespective of outcome, was determined in a comprehensive survey of both women and medical centres during successive 4-week periods in four areas of the Paris region, France. Blood samples were tested anonymously for antibodies to human immunodeficiency virus (HIV)-1 and HIV-2. Of the 11,593 blood samples 0.40% (95% confidence interval [CI] 0.28-0.51) were positive for HIV-1 and 0.02% (95% binomial interval [BI] 0.002-0.065) for HIV-2. Seroprevalence was higher among women with ectopic pregnancy (2%) (95% BI 0.24-7.04); the rate in women having an elective or therapeutic abortion was more than twice that in those delivering babies (0.70% vs 0.28%, p less than 0.05, relative risk 2.54, 95% CI 1.36-4.75). Studies with neonatal HIV seroprevalence as a surrogate for HIV prevalence in pregnant women would underestimate prevalence in these women.

Abortion, Therapeutic↗
PubMed1992

Incorporation of 15N from L-leucine into isoleucine by rat brain cerebral cortex slices.

The fate of leucine nitrogen in the central nervous system was investigated by incubating rat cerebral cortex slices in the presence of 0.5 mM each of L-[15N]-leucine, L-isoleucine, and L-valine. Analysis of the slices and incubation media for free amino acids by gas chromatography-mass spectrometry revealed that the 15N from leucine is incorporated into isoleucine only. No 15N was detected in valine or any other amino acid. These results suggest that leucine, valine, and their corresponding aminotransferases may be compartmentalized in brain cerebral cortex.

Amino Acids↗
PubMed1992

Multiple oral administration of a ketoprofen-dextran ester prodrug in pigs: assessment of gastrointestinal bioavailability by deconvolution.

Deconvolution has been applied to estimate the in vivo dissolution/release process of ketoprofen from a ketoprofen-dextran ester prodrug in pigs. The prodrug was given to three pigs at intervals of 12 hr and in seven doses corresponding to 4 mg ketoprofen/kg body weight. Frequent blood sampling was carried out at the first, third, and seventh intervals. Plasma steady-state concentrations of ketoprofen following the prodrug administration were between 2 and 4 micrograms/ml. The reference consisted of a single p.o. dose of parent ketoprofen (4 mg/kg body weight). For each pig the response following the multiple dosing was deconvolved with the reference response using an algebraic deconvolution procedure adopted from the literature. The obtained cumulated in vivo dissolution/release profiles revealed similar release rates for the three pigs and similar extents of release (59, 70, and 65%). The mean in vivo dissolution/release times (MDT) were calculated to be 5.4, 6.1, and 5.7 hr, respectively. In conclusion, following administration of the dextran prodrug the plasma concentration curves and the dissolution/release profiles are uniform, with small interindividual variations.

Administration, Oral↗
PubMed1992

Macromolecular prodrugs. XX. Factors influencing model dextranase-mediated depolymerization of dextran derivatives in vitro.

Endo-dextranase-mediated depolymerization of dextran and dextran derivatives under various experimental conditions in vitro was determined. By a simultaneous determination of Mn and MW of dextrans treated with the enzyme in aqueous buffer, an initial increase of the polydispersity of the polysaccharide sample was observed, indicating that dextranase cleaved the dextran molecules into chains which differed significantly in length. A pH optimum of 5 for the enzyme action was found. However, in the pH range 5-8, which prevails in the colon, the initial depolymerization rates differed by a factor of less than 2. Dextranase treatment of a dextran sample resulted in a constant increase of the concentration of terminal reducing glucose residues per time unit suggesting, that the initial depolymerization reaction followed zero-order kinetics. For degrees of substitution below 12 the efficacy of dextranase fragmentation of dextran conjugates decreased almost linearly with increasing DS. The chemical nature of the attached drug did not significantly affect the depolymerization rates. Maximally depolymerized dextran derivatives were obtained by the combined action of dextranase and various alpha-glucosidases. Treatment of such solutions with: a) model esterases b) 80% plasma and c) 20% liver homogenate did not give rise to an acceleration of the initial drug regeneration, as compared to identical experiments carried out in pure buffer solution (pH 7.4 and 37 degrees C).

Animals↗
PubMed1991

Translocation (14; 18) and (8; 22) in three patients with acute leukemia/lymphoma following centrocytic/centroblastic non-Hodgkin's lymphoma.

Three patients with centrocytic/centroblastic lymphoma developed a rapidly fatal leukemic transformation of the disease after a transient remission. At the time of transformation, cytogenetic analysis revealed in all patients abnormal karyotypes with coexistence of t (14; 18) and t (8; 22). Molecular analysis in one patient showed rearrangement of the BCL 2 oncogene and c-myc m-RNA expression. These findings imply that translocation t (14; 18) was present during the first phase of the disease and that acquisition of translocation t (8; 22) was accompanied by leukemic transformation.

Acute Disease↗
PubMed1991

Photochemistry of quinolylmethylisothioronium salts. Guanine selective DNA photocleavage reagents.

Quinolylmethylisothioronium salts (1a and 4a) cleave DNA upon irradiation. The cleavage is more than 10-fold enhanced by piperidine treatment and subsequently shows a high preference for guanines. Photolysis of 1a, 2a and 4a in water at lambda greater than 300 nm resulted in photoheterolysis. Irradiation of 1a in 2-propanol gave only products from photohomolysis, irradiation of 1a in methanol and 2a and 4a in 2-propanol resulted in products from both photoheterolysis and photohomolysis. Quantum yields for the disappearance of 1a in water and 2-propanol were determined. The presence or absence of oxygen had no effect in water, whereas oxidation products were observed upon irradiation in methanol and 2-propanol in the presence of oxygen. The guanine specific DNA photoreaction is proposed to take place by alkylation at N7 via the quinolylmethyl carbocation and thus to represent a photoalkylation.

Base Sequence↗
PubMed1991

Diagnostic quality and complications of hysterosalpingography: oil- versus water-soluble contrast media--a randomized prospective study.

In a prospective randomized study of 417 patients, side effects and complications of contrast media and the diagnostic quality of images obtained after hysterosalpingography (HSG) were evaluated after use of diatrizoate meglumine (104 patients), ioxaglate (105 patients), iohexol (105 patients), or ethiodized poppy-seed oil (103 patients). The authors detected no differences among these groups in the prevalence of pain during HSG. The prevalence of lower abdominal pain and vaginal bleeding after HSG was significantly lower in the group that received ethiodized poppy-seed oil than in the three other groups. The prevalence of pelvic infection or inflammation was significantly lower with ethiodized poppy-seed oil than with water-soluble media. All contrast media provided acceptable diagnostic image quality with regard to fallopian tubes, peritoneal spill, and intraperitoneal distribution. Visualization of the uterine cavity and ampullary rugae was significantly better with water-soluble media than with ethiodized poppy-seed oil, which was associated with a high conception rate and which the authors consider preferable for HSG.

Contrast Media↗
PubMed1991

Therapeutic effect of hysterosalpingography: oil- versus water-soluble contrast media--a randomized prospective study.

In a prospective randomized study, the number of pregnancies after hysterosalpingography (HSG) was estimated in 398 patients who had been infertile for longer than 1 year. Iohexol was used in 101 patients, ioxaglate in 102 patients, diatrizoate meglumine in 97 patients, and ethiodized poppy-seed oil in 98 patients. Ten months after HSG, the patient, referring physician, and/or hospital department was consulted for information about pregnancies. Questionnaires were obtained from the patients who became pregnant during the waiting period of 3 months. No differences in demographic parameters, infertility status, or diagnosis made with HSG were detected among the four contrast media groups. Significantly more patients became pregnant after HSG in the ethiodized poppy-seed oil group than in the three water-soluble contrast media groups (P less than .01). When only intrauterine pregnancies resulting in full-term births were considered, significant differences in pregnancy rates between the oil-soluble and the water-soluble contrast media groups became more obvious. In the group that received ethiodized poppy-seed oil, almost one-third of the infertile women had normal pregnancies and childbirths after HSG.

Contrast Media↗
PubMed1991

Stability of ketoprofen-dextran ester prodrugs in homogenates of various segments of the pig GI tract.

Initial velocities of ketoprofen formation from ketoprofen-dextran ester prodrugs incubated in homogenates of various segments of the pig GI-tract were determined. Enzyme-mediated drug release was found in caecum and colon homogenates with their contents, whereas release rates in the stomach, duodenum, jejunum and ileum homogenates were comparable to those determined in pure buffer solutions of identical pH. In colon homogenates adjusted to various pH values between 6.0 and 7.9, little variation in release rates was observed. However, the contribution of enzyme-catalyzed drug regeneration to the overall initial velocity of ketoprofen formation increased significantly as a function of decreasing pH. The presence of several antibiotics and betamethasone in colon homogenates did not affect the drug activation process, whereas the addition of various enzyme inhibitors slowed down the ketoprofen release rates. During incubation in colon homogenates the average molecular weight of the dextran esters decreased. The drug release may therefore involve an initial fragmentation of the drug-liganded dextran chains carried out by dextranases secreted from the microflora which reside in the pig's large bowel.

Animals↗
PubMed1991

Bioavailability of ketoprofen from orally administered ketoprofen-dextran ester prodrugs in the pig.

The bioavailability of ketoprofen after oral administration of aqueous solutions of various ketoprofen-dextran ester prodrugs in pigs was assessed. Conjugates derived from dextran fractions in the molecular weight range 10,000-500,000 were employed. Compared to the administration of an oral solution of an equivalent dose of parent ketoprofen, the average absorption fractions for the different prodrugs ranged from 100 to 67%. Relatively small inter-individual variation of ketoprofen bioavailability was observed. Apparently, the molecular size of the employed dextran transport group only has a minor influence on the pharmacokinetic parameters. The ketoprofen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of ketoprofen appearance in the blood (2-3 h). Quite similar results were obtained from identical experiments carried out in the pig, employing naproxen-dextran esters. Thus, the present study adds support to a more versatile application of the dextran ester prodrug approach to providing selective colon delivery of drugs possessing a carboxylic acid functional group.

Administration, Oral↗
PubMed1991

Macromolecular prodrugs. IXX. Kinetics of hydrolysis of benzyl dextran carbonate ester conjugates in aqueous buffer solutions and human plasma.

Benzyl carbonate esters of dextran with varying degrees of substitution have been synthesized. The kinetics of the hydrolytic cleavage of the carbonate ester bond in aqueous solution within the pH range 0.44-10.46 (37 degrees C) has been investigated. The degradation reactions followed pseudo-first-order kinetics and a rate expression encompassing hydrogen ion-, hydroxide ion- and water-catalyzed hydrolysis of the dextran conjugates was derived. No influence of the degree of substitution on the reaction rates was observed. In alkaline solution a slightly enhanced lability of trifluorethyl benzyl carbonate ester compared to the benzyl dextran carbonate esters was observed, indicating a lack of any significant intramolecular catalytic effect in the hydrolysis of the dextran esters. Almost identical rates of liberation of benzyl alcohol were found in 80% human plasma and aqueous buffer of pH 7.4, indicating the lack of enzyme-mediated cleavage of the dextran carbonate ester bond.

Buffers↗
PubMed1990

Lymphocyte proliferative responses to soluble and liposome-conjugated envelope peptides of HIV-1.

The proliferation of lymphocytes from HIV-seronegative (HIV Ab-) and seropositive (HIV Ab+) individuals in response to two synthetic peptide epitopes of HIV envelope glycoproteins (ENVgp) was evaluated as an index of cell-mediated immunity in infected individuals. All HIV Ab- and most HIV Ab+ individuals' lymphocytes failed to proliferate in primary cultures in response to the two soluble HIV ENVgp peptides, ENVP346 and ENVP466 even in the presence of rIL-2. After stimulation with liposome-conjugates of ENVP346 or ENVP466 and soluble rIL-2, however, CD4 lymphocytes from some HIV Ab+ individuals were able to proliferate. Significantly higher frequencies of rIL-2-augmented proliferative responses to liposome-conjugated ENVP346 or ENVP466 were observed in HIV Ab+ asymptomatic individuals as compared to patients with AIDS-related conditions or AIDS. These studies indicate that the conjugation of HIV peptides or proteins to liposomes and stimulation with rIL-2 may enhance cell-mediated responses to these peptides.

AIDS-Related Complex↗
PubMed1990

Intravenous urography with a new non-ionic contrast media in a clinical phase III study: iopentol vs iohexol.

The safety and diagnostic efficacy of iopentol 300 mg I/ml were compared with iohexol 300 mg I/ml in 300 patients submitted for urography. The study was carried out as a double-blind, randomised parallel study where 149 patients received iopentol and 150 patients iohexol. There were no significant differences between the patients receiving the two contrast media with regard to demographic parameters, rate of injection or total dose of injected contrast media. No changes in blood pressure and no clinically important changes in heart rate were detected in the two groups. No serious adverse effects occurred. Seven patients (5%) in the iohexol and 12 patients (8%) in the iopentol group experienced adverse effects other than a sensation of warmth. Fourteen iohexol patients (9%) and 18 iopentol patients (12%) experienced warmth related to the contrast injection. Excellent films were obtained in most patients and no difference in diagnostic quality between iopentol and iohexol was observed.

Adult↗