Search PubMed⌕ Search

Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 307 records · Page 17Linked to original sources

A study of amikacin given once versus twice daily in serious infections.

Forty-five mostly elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin 11.0 or 15.0 mg/kg administered in a single daily dose as an intravenous, short-term infusion or with amikacin 7.5 mg/kg administered twice daily in the same way. The results indicate that administration of amikacin 15 mg/kg in a single daily dose should be a practical and safe principle of administration. However elderly patients often have reduced creatinine clearance and should preferably be given a lower dose of 11 mg/kg bw. The risk of nephrotoxicity did not increase, but conclusions on ototoxicity and clinical efficacy cannot be drawn from this limited study. This should be considered as an initial part of a future multicentre trial.

Aged↗

Subpopulations of variants resistant to imipenem in Pseudomonas aeruginosa.

Selection and regrowth of resistant variants, which were present in low frequencies in the initial inoculum, was seen when large inocula of Pseudomonas aeruginosa were incubated with imipenem. The selective growth of resistant variants resulted in an inoculum effect, and an increase in MIC with longer incubation. When large inocula taken from strains that had been classified as sensitive in conventional MIC determinations were incubated with 4, 8 and 16 mg/l imipenem, 62%, 24% and 10%, respectively, of the strains regrew. None of the resistant variants thereby selected showed cross resistance to other beta-lactam antibiotics or aminoglycosides. In vitro evaluation of regrowth of resistant variants may be justified when choosing imipenem for therapy in the treatment of serious P. aeruginosa infections.

Adenosine Triphosphate↗

Patients' experience of transvaginal follicle aspiration under local anesthesia.

The development of vaginal ultrasound transducers has facilitated ovum pick-up (OPU) by providing higher precision and less trauma than are found with laparoscopy and other ultrasound-assisted techniques. In order to evaluate the patients' acceptance, 65 patients were asked to answer a questionnaire about their experience with the procedure. The punctures were executed with specially designed needles introduced through a needle guide attached to a vaginal transducer with a frequency of 7 MHz (Brüel & Kjaer, Denmark). The anesthesia consisted of a light premedication and a paracervical block. If needed, a small dose of sedative was given intravenously intraoperatively. The patients classified their pain experience within the day of the puncture on a four-grade scale. Their statements were compared to the physician's opinion of the discomfort caused. Oocytes were retrieved from all patients. Fifty-one patients answered the questionnaire, of whom five found the OPU painful. In two cases the physician underestimated the patients' pain experience. The mean time required for the procedure was 16 min/OPU. We conclude that transvaginal ultrasound-guided OPU is well accepted by most patients under local anesthesia and that it is a rapid and accurate procedure.

Anesthesia, Local↗

Chronic active hepatitis in Sweden. The etiologic spectrum, clinical presentation, and laboratory profile.

An epidemiologic study covering about 1/3 of the adult Swedish population showed an annual incidence of chronic active hepatitis (CAH) of 1.6 per 100,000. At least 45% had a viral cause of their CAH, the proportion being distinctly higher in large cities than in rural ones. Drugs, alcohol, and metabolic disorders were rarely identified as etiologic factors. The prevalence of ulcerative colitis and gluten enteropathy was remarkably high in idiopathic CAH. Compared with antibody-negative patients with idiopathic CAH, antibody-positive patients showed higher rates of the female sex, IgG increase, anti-HBs negativity, compliance with the Mayo criteria for treatment, and absence of previous episode of jaundice. Furthermore, in autoantibody-negative idiopathic CAH the prevalence of anti-HBs antibodies was at least three times greater than in the Swedish population, suggesting a viral cause of some forms of idiopathic CAH, a suggestion supported by the clinical pattern of the disease.

Adult↗

Activation of inflammatory systems during cardiopulmonary bypass.

"Whole body inflammation" induced by cardiopulmonary bypass may play a role in the pathogenesis of postoperative complications after open-heart surgery. The inflammatory response, in terms of complement activation and release of granular proteins from neutrophil granulocytes, was investigated in six patients undergoing aortocoronary bypass surgery. Complement activation was demonstrated as well as substantially increased plasma levels of lactoferrin and myeloperoxidase--two granulocyte factors. The activation of inflammatory systems probably takes place on the artificial surfaces of the extracorporeal device. The biocompatibility of these components therefore should be further studied.

Aged↗

Danazol concentrations in human ovarian follicular fluid and their relationship to simultaneous serum concentrations.

Danazol concentrations in follicular fluid and serum were studied in eight women scheduled for laparoscopy because of suspected endometriosis. In order to obtain some variation in follicular maturity, danazol administration was started 2 to 7 days before the expected day of ovulation. A total of nine doses were given, i.e., 200 mg four times daily for 2 days; the last 200-mg dose was given 3 hours before the laparoscopy during which the follicular fluid from the dominant follicle was aspirated. Peripheral venous blood samples were drawn before, during, and after laparoscopy. Danazol concentrations were assayed by means of a high-performance liquid chromatography method. At the time of follicular aspiration, the mean concentration of danazol was estimated at 96 ng/ml in serum and at 71 ng/ml in follicular fluid, i.e., an average of 73% of the simultaneous serum concentration. The data suggest that even short-term therapy with danazol is likely to produce intrafollicular drug concentrations that have a direct inhibitory effect on follicular steroidogenesis.

Adult↗

Characterisation of the ribosomal binding site for eukaryotic elongation factor 2 by chemical cross-linking.

Ribosomal complexes containing elongation factor 2 (EF-2) were formed by incubation of 80 S ribosomes in the presence of EF-2 and the non-hydrolysable GTP analogue GuoPP[CH2]P. The factor was covalently coupled to the ribosomal proteins located at the factor binding site, by treatment with bifunctional reagents. After isolation of the covalent EF-2.ribosomal protein complexes, the proteins were labelled with 125I and the introduced covalent links cleaved. The ribosomal proteins were identified by electrophoresis in two independent two-dimensional gel systems, followed by autoradiography. After cross-linking with bis(hydroxysuccinimidyl) tartrate (4 A between the reactive groups), protein S3/S3a, S7 and S11 were found as the major ribosomal proteins covalently linked to EF-2. The longer reagent, dimethyl 3,8-diaza-4,7-dioxo-5,6-dihydroxydecanbisimidate (11 A between the reactive groups), covalently coupled proteins S7, S11, L5, L13, L21, L23, L26, L27a and L32 to EF-2. After cross-linking with dimethyl suberimidate (9 A between the reactive groups) proteins S3/3a, S7, S11, L5, L8, L13, L21, L23, L26, L27a, L31 and L32 were identified as belonging to the EF-2-binding site. The results indicate that the ribosomal domain interacting with EF-2 is located on both the small and the large ribosomal subunit close to the subunit interface.

Animals↗

Refinement of the solution structure of the DNA hexamer 5'd(GCATGC)2: combined use of nuclear magnetic resonance and restrained molecular dynamics.

The solution structure of the self-complementary DNA hexamer 5'd(GCATGC)2 comprising the specific target site for the restriction endonuclease Sph 1 is investigated by using nuclear magnetic resonance spectroscopy and restrained molecular dynamics. All the nonexchangeable proton resonances are assigned sequentially, and from time-dependent nuclear Overhauser enhancement measurements a set of 158 approximate interproton distances are determined. These distances are used as the basis of a structure refinement using restrained molecular dynamics in which the interproton distances are incorporated into the total energy function of the system in the form of an effective potential term. Two restrained molecular dynamics simulations are carried out, starting from classical B- and A-DNA [atomic root mean square (rms) difference 3.3 A]. In both cases convergence is achieved to essentially identical structures satisfying the experimental restraints and having a root mean square difference of only 0.3 A between them, which is within the rms fluctuations of the atoms about their average positions. These results suggest that the restrained molecular dynamics structures represent reasonable approximations of the solution structure. The converged structures are of the B type and exhibit clear sequence-dependent variations of helical parameters, some of which follow Calladine's rules and can be attributed to the relief of interstrand purine-purine clash at adjacent base pairs. In addition, the converged restrained dynamics structures appear bent with a radius of curvature of approximately 20 A. This bending appears to be due almost entirely to the large positive base roll angles, particularly at the Pyr-Pur steps. Further, the global and local helix axes are not coincident, and the global helix axis represents a superhelical axis which the bent DNA, when extended into an "infinite" helix by repeated translation and rotation, wraps around.

Calorimetry↗

Protein dynamics. A time-resolved fluorescence, energetic and molecular dynamics study of ribonuclease T1.

Studies using time-resolved fluorescence depolarization were performed on the internal motion of Trp 59 of ribonuclease T1 (EC 3.1.27.3) in the free enzyme, 2'-GMP-enzyme complex and 3'-GMP-enzyme complex. The Trp 59 motion was also studied in the free enzyme using molecular dynamics simulations. Energetic analysis of activation barriers to the Trp 59 motion was performed using both the transition state theory and Kramers' theory. The activation parameters showed a dependence on solvent viscosity indicating the transition state approach in aqueous solution to be inadequate. When taking solvent viscosity contributions into account agreement between the transition state and Kramers' theories was obtained. The results indicate the three enzyme forms to have different conformations with the free enzyme and 3'-GMP-enzyme complex being similar. Comparison of the experimental and theoretical results showed a good agreement on the Trp 59 motion in the free enzyme. Trp 59 appears to vibrate rapidly, with a relaxation time of the order of 1 ps, within free space in the protein matrix and to have a slower motion, with a relaxation time of the order of 100 ps, which is related to breathing of the surrounding protein matrix. Molecular dynamics results indicate high mobility in regions of the enzyme involved in the interaction with the guanine base of the inhibitor or substrate while much lower mobility occurred in residues involved in the catalytic mechanism of ribonuclease T1.

Aspergillus oryzae↗

The ribosomal binding site for eukaryotic elongation factor EF-2 contains 5 S ribosomal RNA.

The possible location of RNA in the ribosomal attachment site for the eukaryotic elongation factor EF-2 was analysed. Stable EF-2 X ribosome complexes formed in the presence of the non-hydrolysable GTP analogue GuoPP[CH2]P were cross-linked with the short (4 A between the reactive groups) bifunctional reagent, diepoxybutane. Non-cross-linked EF-2 was removed and the covalent factor-ribosome complex isolated. No interaction between EF-2 and 18 S or 28 S rRNA could be demonstrated. However, density gradient centrifugation of the cross-linked ribosomal complexes showed an increased density (1.25 g/cm3) of the factor, as expected from a covalent complex between EF-2 and a low-molecular-weight RNA species. Treatment of the covalent ribosome-factor complexes with EDTA released approx 50% of the cross-linked EF-2 from the ribosome together with the 5 S rRNA X protein L5 complex. Furthermore, the complex co-migrated with the 5S rRNA X L5 particle in sucrose gradients. Polyacrylamide gel electrophoresis showed that EF-2 was directly linked to 5 S rRNA in the 5 S rRNA X L5 complex, as well as in the complexes isolated by density gradient centrifugation. No traces of 5.8 S rRNA or tRNA could be demonstrated. The data indicate that the ribosomal binding domain for EF-2 contains the 5 S rRNA X protein L5 particle and that EF-2 is located in close proximity to 5 S rRNA within the EF-2 X GuoPP[CH2]P X ribosome complex.

Animals↗

Use of a vaginal transducer for oocyte retrieval in an IVF/ET program.

Sonography has proved to be an important diagnostic and operative instrument in an in-vitro fertilization and embryo transfer (IVF/ET) program. In some IVF/ET programs the technique has even replaced laparoscopy for oocyte retrieval. To date, transvesical follicle aspiration has been the main technique for ultrasound-guided oocyte pick-up. However, this technique has some disadvantages. Therefore, we have developed a transvaginal ultrasound-guided puncturing technique. A new high-frequency vaginal sector transducer was utilized (Brüel & Kjaer). This new transducer, equipped with a needle guide, changed the oocyte retrieval into a simple, safe, and rapid procedure that can be performed under local anesthesia without any discomfort for the patient.

Female↗

Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?

In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10(-4) M and physostigmine 10(-4) M significantly increased the release of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10(-6) M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10(-5) M significantly increased the 3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.

Acetylcholine↗

Fertilization and embryo development of oocytes obtained transvaginally under ultrasound guidance.

The widespread use of ultrasound for follicle development assessment and ovum pickup has raised concerns about the theoretical possibility of adverse effects on oocyte function. Studies in other species do not demonstrate any adverse effects when using sonic energies as those presently used in diagnostic ultrasound. However, no data are available concerning the effects of diagnostic ultrasound on human preovulatory oocytes. This study was conducted to determine whether there were any adverse effects on the reproductive function of oocytes using transvaginal ultrasonography. No effect on fertilization and subsequent cleavage of oocytes was demonstrated. This method can, therefore, be recommended for follicle assessment and as a better alternative to laparoscopy for oocyte retrieval.

Adult↗

Clinical experience in an in vitro fertilization and embryo replacement program of a new method for analysis of urinary estrogens.

The clinical experience in an IVF/ER program of a newly developed commercial kit (Estradiol enzymatique; BioMerieux) to determine urinary estrogens enzymatically, is reported. The study included 157 cycles, and the main indication for treatment was infertility due to tubal factor. Follicular development was stimulated in most cases by a combination of clomiphene citrate, human menopausal gonadotropin and chorionic gonadotropin. In addition to the previously used method to monitor follicular growth, ultrasound, daily urinary estrogens (estradiol + estrone) levels were assayed. A correlation between the pattern of urinary estrogen and the clinical results was found. In cycles with continuously rising estrogen up to the time of hCG administration a higher rate of in vitro fertilization and clinical pregnancies were obtained as compared to cycles where urinary estrogen declined or levelled off. It is concluded that this enzymatic assay of urinary estrogens is a good alternative to increase the precision of follicle monitoring when radioimmunological assay of serum estradiol levels cannot be obtained on a daily routine basis.

Chorionic Gonadotropin↗

Epidemiology of hepatitis B in Somalia: inference from a cross-sectional survey of serological markers.

Hepatitis B markers were determined by radioimmunoassay in 383 adults from different areas of Somalia and in 135 pregnant females and 428 children from Mogadishu. The highest incidence of HBsAg among adults was among nomadic males (20/85; 23%). The frequencies were lower in males from the agricultural and coastal area, i.e. 16/93 (17%) and 14/98 (14%) respectively. The lowest frequency of HBsAg was among women from the coastal area (6/72; 8%). Among the pregnant women 14 were positive for HBsAg, none of whom had HBeAg. Low levels of positivity for HBsAg were found both among children under 4 years and among those between 4 and 13 years of age - 3/94 (3%) and 5/128 (4%) respectively. In the age group 15-19 years, 50% showed seroconversion from HBeAg to anti-HBe. 7 out of 41 HBsAg carriers of ages over 20 had HBeAg. Early seroconversion from HBeAg to anti-HBe and a low level of HBsAg positivity in children indicate that vertical transmission is not important in Somalia. The low frequency of HBsAg in Mogadishu children may have one of the following explanations: (i) the infection occurs during adolescence, (ii) Mogadishu is a low-prevalence area and the examined adults were not born in Mogadishu, or (iii) a change in hepatitis B epidemiology has taken place in the area during the last 2 decades and the relatively higher prevalence of HBsAg in adults might reflect higher rates of infection in their childhood.

Adolescent↗

Mutagenicity of pan residues and gravy from fried meat.

Lean pork meat was fried with or without the addition of frying-fat at 200 or 250 degrees C. The pan residues were collected by washing the hot pan with boiling water. When producing thickened gravy the water was substituted by a mixture of water and flour, milk and flour or cream and flour. The basic extracts were tested for mutagenicity in Ames' Salmonella test on strain TA98 with the addition of S9 mix. High amounts of mutagenicity were found in all samples. The amounts of mutagenicity in the pan residues were at a comparable level of the amounts found in the meat crusts. Thickening of the gravy caused only small changes in the mutagenicity.

Animals↗

Frequencies of variants resistant to different aminoglycosides in Pseudomonas aeruginosa.

The MICs of aminoglycosides for Pseudomonas aeruginosa are higher than those for Enterobacteriaceae and the number of variants resistant to high concentrations of aminoglycosides is greater in P. aeruginosa than in Escherichia coli. However, when the frequencies of resistant variants at different multiples of the MIC were calculated, these frequencies were similar in P. aeruginosa and E. coli. When large inocula of strains of P. aeruginosa, which were classified as sensitive in conventional MIC determinations, were incubated with amikacin, gentamicin, netilmicin or tobramycin at the break-point concentrations between sensitivity and resistance, 82%, 90%, 90% and 15%, respectively, of the strains regrew. The corresponding percentages for Enterobacteriaceae were much lower. The clinical relevance of this pronounced regrowth of P. aeruginosa is discussed.

Aminoglycosides↗