Biomedical subjects

A Voss

Publications and source records attributed to A Voss.

At least 163 records · Page 9Linked to original sources

PubMed1994

Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. II. Kinetics of allopurinol, oxipurinol, and hydrochlorothiazide.

The kinetics of allopurinol and hydrochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formula diet with RNA supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1-24. Hydrochlorothiazide (50 mg daily) was added to days 11-21. On day 43 a single oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration-time profiles of allopurinol and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In addition, 24-h plasma concentrations of oxipurinol were measured repetitively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, mean Cmax was not altered on hydrochlorothiazide treatment (13.8 +/- 1.4 micrograms/ml and 14.7 +/- 2.6 micrograms/ml, respectively); mean AUC0-24 was 259 and 290 micrograms h-1 ml-1, respectively. The small difference in AUC0-24 values does not explain the increase in plasma uric acid concentration during hydrochlorothiazide treatment, nor do the variations in allopurinol and hydrochlorothiazide kinetics.

Administration, Oral↗

PubMed1994

Methicillin-resistant Staphylococcus aureus in Europe.

In order to obtain pan-European data on methicillin-resistant Staphylococcus aureus (MRSA), 43 laboratories from ten European countries each screened 200 consecutive Staphylococcus aureus isolates for methicillin resistance. Only one isolate per patient was permitted. All participants used a uniform oxacillin-supplemented screening plate. MRSA isolates were sent to Munich for reconfirmation and further susceptibility testing. Phage typing of the MRSA strains was performed in Denmark. Of the 7,333 Staphylococcus aureus strains screened, 936 (12.8%) were methicillin resistant. The proportion of MRSA in the various European countries ranged from < 1% in Scandinavia to > 30% in Spain, France and Italy. Rates of resistance to the non-glycopeptide antibiotics were lowest for rifampin and highest for ciprofloxacin. Sixty percent of the methicillin-resistant strains originated from patients in surgical and medical departments, with wounds being the most common isolation source. MRSA was found more frequently in intensive care patients. Only 13% of the strains were non-typable, and 76% of the isolates belonged to phage group III. For each area phage typing detected one or a few dominating (epidemic) types, but 46% of the strains did not belong to these types; the MRSA population is thus a mixture of epidemic and non-epidemic strains. MRSA seems to be a growing problem, especially in southern Europe, where incidence and rates of antibiotic resistance are alarmingly high.

Anti-Bacterial Agents↗

PubMed1994

Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma. Comparison with classifications and prognosis.

The relevance of silver-stained NORs for classifications and prognosis was investigated in breast tissue. Paraffin sections from 137 cases of invasive ductal breast carcinomas and 12 cases with non-tumorous ductus epithelium as controls were stained according to a modified technique and analysed. From the cancer cases follow-up data up to 10 years (45 to 165 months) and in addition clinical, histological and several DNA distribution parameters were available. The nuclei and the silver grains were measured by means of a semiautomatic image analysis system. Significant differences in AgNOR features were found between controls and diploid tumors (p < or = 0.001), diploid and aneuploid tumors (p < or = 0.001), Bloom-Richardson-gradings I, II, and III (p < or = 0.001), and between the tumor cells from patients developing metastases within 5 years and those without (p < or = 0.002). The prognostic significance of AgNORs was estimated using Cox regression analysis. Four AgNOR features were correlated significantly with survival time. In a multivariate approach offering all parameters available an AgNOR parameter (CV of relative area AgNORs) ranked at the third position beyond the SD of DNA distribution and pTNM-staging. Considering the metastases-free interval of patients the same AgNOR feature showed an independent prognostic validity.

Adult↗

PubMed1994

Investigation of the sequence of colonization and candidemia in nonneutropenic patients.

Among neutropenic patients with hematologic malignancies, candidemia has been shown to arise typically from autoinfection after colonization. In patients without neutropenia, we examined the similarities of strains colonizing or infecting various body sites and those subsequently causing Candida bloodstream infections. Strain similarity was examined by karyotyping and restriction endonuclease analysis of genomic DNA (REAG) by using two restriction enzymes (SfiI and BssHII). The banding patterns of 42 isolates from 19 patients were independently evaluated in a blinded fashion by three observers. The interobserver reliability measured with a generalized kappa statistic was 0.59 for karyotyping, 0.84 for REAG with SfiI, and 0.88 for REAG with BssHII (P < 0.001 for each). REAG classified the initial colonizing or infecting isolate and subsequent blood isolates as identical in 16 patients (84%). The mean duration of colonization or infection prior to a positive blood culture was 5 and 23 days in patients infected with related and unrelated isolates, respectively (P = 0.14; 95% confidence interval = -14.5 to 50.5). Karyotyping results matched the REAG results for isolates from 14 of the 19 patients (74%). In patients infected with identical isolates, the initial isolate was most frequently recovered from the urine (n = 5) or vascular catheter tips (n = 4). In the five subjects with organisms showing disparate results between the methods, karyotyping revealed different banding patterns, whereas REAG suggested that the isolates were identical. Candida colonization or infection with an identical strain frequently precedes bloodstream infection in nonneutropenic patients. Future studies should evaluate whether patients at high risk for candidemia and who have vascular catheter or urine samples that are positive for a Candida on culture should be treated empirically.

Adult↗

PubMed1994

[New methods for the detection of high risk patients in cardiology].

Common non-invasive diagnostic methods like Holter monitoring or the analysis of high-resolution ECG and heart rate variability are unable to accurately assess the individual risk for sudden cardiac death, since they describe only statistical, linear or strictly periodic parameters. Using new methods of non-linear dynamics one can now calculate parameters which much better describe the dynamic behaviour of complex systems. The application of these new methods should therefore lead to an improved identification of high-risk patients. The results of this first pilot investigation show on the one hand that ventricular arrhythmias are quick detectable using phase space plots, and on the other hand that the new methods of non-linear dynamics could lead to a new classification of high-risk patients.

Adult↗

PubMed1994

[Fingerprinting with the polymerase chain reaction: confirmation of a Enterobacter cloacae epidemic in a neonatal intensive care unit].

Between end December 1993 and end January 1994 a cluster of children infected/colonized with Enterobacter cloacae was seen in the neonatal intensive care unit of the University Hospital Nijmegen. The results of the epidemiological investigation are reported, which was aimed to differentiate between a random cluster of endogenously acquired Enterobacter strains and those possibly acquired exogenously via cross-infection. 5 isolates of the 7 patients were available for fingerprinting using interrepeat PCR. According to the fingerprint pattern, 4 of these isolates were identical, thereby suggesting cross-infection among the children. 3 neonates were colonized/infected with genotypically different isolates, suggesting that the infection/colonization developed endogenously. A control strain isolated from a patient at another ward showed the same genotype as the outbreak isolates. The transmission took probably place through one of the surgeons who, among all possible health care workers, were the only professional group treating patients in both units.

Cross Infection↗

PubMed1993

Bioequivalence of allopurinol preparations: to be assessed by the parent drug or the active metabolite?

Allopurinol is converted almost completely into a single active metabolite, oxipurinol, which has the same therapeutic pattern but a much longer elimination half-life than the parent compound. Therefore both allopurinol and oxipurinol were evaluated in our bioequivalence study in healthy volunteers comparing two allopurinol brands. Bioequivalence determination was based on the 90% confidence intervals (CI) of the area under the plasma concentration time curve from time zero to infinity (AUC0-infinity), of the area from time zero to the last measurable plasma concentration (AUC0-t (last)), and Cmax. Because of the lack of compound-specific criteria we used conventional limits for the bioequivalence range. Under these conditions the brand chosen as test preparation was judged to be bioequivalent to the reference form with respect to the extent of bioavailability, AUC0-infinity, and AUC0-t (last) of the parent drug. The CI of Cmax of allopurinol slightly exceeded the upper limit of 130%, so that bioequivalence was not confirmed with regard to the rate of bioavailability of the parent compound. The CI values of both AUC and Cmax of the active metabolite were tighter than those of allopurinol. In addition, the CI values of Cmax of oxipurinol were smaller than those of the corresponding AUC. As a consequence the test drug can clearly be accepted as bioequivalent, based on metabolite data. Since the active metabolite is of greater therapeutic significance than the parent drug, assessment of the bioequivalence of allopurinol preparations needs to be based on oxipurinol rather than allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection.

The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. In order to detect possible sources of error IMEG signals were recorded in heterotopic neck hearts in ten beagle dogs. Immunosuppression was based on cyclosporin A. The rejection process was followed by IMEG registrations as well as by serial myocardial biopsies. Intramyocardial electrogram recordings were made via three unipolar and three bipolar leads obtained from screw-in electrodes in both ventricles and the apex of the allograft. A 10% voltage drop was used as an indicator of rejection. In four dogs, the first rejection episode was treated with methyl-prednisolone and the therapy's success was monitored by IMEG and repeat biopsy. At autopsy the histology of each electrode circumference was correlated with the corresponding IMEG. The average sensitivity of a single lead was not acceptable (unipolar: 28%, bipolar: 47%). When the voltages of different leads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 x bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 h. We conclude that in moderate allograft rejection (grade 2/3a ISHT classification), the rejection-related changes of intramyocardial ECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance adequate diagnostic reliability.

Animals↗

PubMed1993

In vivo bonding of orthodontic brackets with glass ionomer cement.

The adhesion of orthodontic bracket bases was examined in vivo 24 to 32 hours after bonding with glass ionomer cement (GIC). In contrast to bonding with composite resin, with GIC there is no need to etch the enamel surface of the tooth. Conventional metal brackets with mesh pad, bonded with GIC, showed an average shear bond strength of 3.6 +/- 1.1 MPa, approximately one-fourth the bond strength of composite resin. Fracture sites were found exclusively at the mesh/GIC interface. Bonding between GIC and enamel must, therefore, be stronger than bonding between conventional resin and enamel. An experimental attachment with a modified base, consisting of brass rings 4 mm in diameter with a retention groove, was designed. In these experimental cases, fractures were found at the base/GIC interface and at the enamel/GIC interface. Shear bond strength of the experimental base was as high as 5.8 +/- 1.0 MPa. These values approached those of brackets bonded with composite resin and acid etching. Bond strengths of up the 3 MPa which occur during orthodontic treatment were achieved. Clinical trials with GIC bonding thus seem feasible and are being initiated.

Acid Etching, Dental↗

PubMed1993

[Quantitative study of vaginal flora during the menstrual cycle].

The aerobic and facultatively anaerobic vaginal flora of 242 healthy women were examined during menstrual cycles. The most frequently isolated microorganisms at the first premenstrual examination were coagulase-negative staphylococci (61%), followed by enterococci (25%), Gardnerella vaginalis (19%), diphtheroids (12%), group B streptococci (6.8%), Escherichia coli (5.4%) and Candida spp. (4%). The isolation rate of all species, except Candida and Gardnerella vaginalis increased during menstruation. The lowest isolation rate for Staphylococcus aureus was 0.9% prior to menstruation and it increased to 7.6% during menstruation. This may be of relevance with regard to the toxic shock syndrome. Gardnerella vaginalis was isolated in 37% of women at least once during the study, suggesting, that this species belongs to the normal vaginal flora.

Adolescent↗

PubMed1993

Comparison of pulsed-field gel electrophoresis with isoenzyme profiles as a typing system for Candida tropicalis.

Candida species are important nosocomial pathogens, particularly in immunocompromised and critically ill patients. A variety of methods have been used to differentiate strains, but an optimal system has not been established. We compared methods for typing a panel of nine related isolates of Candida tropicalis from an outbreak of sternal wound infections as well as four unrelated control isolates of this species. (The genetic relationships of the nine isolates in the panel had been confirmed previously by restriction fragment analysis.) Typing was undertaken without knowledge of an isolate's origin. Karyotyping by contour-clamped homogeneous electric field (CHEF) gel electrophoresis failed to distinguish between outbreak and control isolates. However, when chromosome-sized DNA was digested with SfiI, EagI, SacII, or NaeI and the fragments were separated by CHEF electrophoresis, the outbreak isolates were readily identified. The isoenzyme profiles of the outbreak isolates were identical and were distinctly different from those of the control isolates. While both isoenzyme profiles and the modified CHEF procedure were discriminatory, the latter is recommended as a relatively convenient and reproducible technique for comparison of types of C. tropicalis.

Acid Phosphatase↗

PubMed1993

Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients.

Mononuclear cells of the lamina propria (LpMNC), isolated from endoscopically taken biopsies of the large bowel from AIDS patients, were analysed for their ability to secrete tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6. Stimulation of LpMNC from normal controls with pokeweed mitogen (PWM) led to a time- and dose-dependent enhancement of TNF-alpha, IL-1 beta and IL-6 secretion. In contrast, PWM stimulation of LpMNC from AIDS patients resulted in only a small increase in TNF-alpha release. Constitutive secretion of IL-1 beta and IL-6 in these patients was already increased to the concentration range of stimulated cells from normal controls and could not be further increased, probably due to maximal in vivo stimulation. Secretion of TNF-alpha, IL-1 beta and IL-6 by peripheral blood monocytes (PBM) and alveolar macrophages from AIDS patients was elevated with or without stimulation compared with normal controls. Obviously, the regulation of TNF-alpha secretion is dependent on the microenvironment. Since it is known that interferon-gamma (IFN-gamma) may induce the production of TNF-alpha, the secretion of this cytokine was examined. Release of IFN-gamma was constitutively and under stimulation lowered in LpMNC from AIDS patients compared with normal controls. Addition of IFN-gamma to LpMNC did not result in enhanced TNF-alpha secretion. Our data indicate a defective function of intestinal mononuclear cells in AIDS patients as shown by the diminished TNF-alpha secretion.

HIV Infections↗

PubMed1993

Metabolism of benzbromarone in man: structures of new oxidative metabolites, 6-hydroxy- and 1'-oxo-benzbromarone, and the enantioselective formation and elimination of 1'-hydroxybenzbromarone.

1. The uricosuric drug benzbromarone is extensively metabolized in man and two main metabolites are formed: the previously characterized 1'-hydroxybenzbromarone (metabolite M1) and an arylhydroxybenzbromarone (metabolite M2) of unknown structure. A dimethyl derivative was isolated from urine after methylation and was characterized by gas chromatography-mass spectrometry (g.l.c.-m.s.) and high resolution nuclear magnetic resonance spectroscopy as 4''-O-methyl-6-methoxybenzbromarone; the structure of M2 therefore is 6-hydroxybenzbromarone. 2. A minor metabolite was similarly characterized as 1'-oxobenzbromarone by comparison with authentic synthetic samples and is a product of biodegradation and not an artifact derived from the in vitro oxidation of 1'-hydroxybenzbromarone. Further minor metabolites were detected and were provisionally characterized by g.l.c.-m.s. after derivatization and include: 2'-hydroxybenzbromarone (an isomer of 1'-hydroxybenzbromarone); 1',6-dihydroxybenzbromarone; dihydroxy-aryl-benzbromarone; and two structure isomers of 6-hydroxybenzbromarone. Debrominated metabolites were not detectable. 3. Benzbromarone is hydroxylated in vivo at the prochiral centre C1' to 1'-hydroxybenzbromarone; analysis of 1'-hydroxybenzbromarone from plasma and urine extracts by h.p.l.c. using a chiral column revealed that two peaks were eluted which showed a mean enantiomeric ratio of 2.1 for plasma and 7.3 for urine; these data demonstrate that the formation and elimination of this metabolite is enantioselective; the absolute configuration of the 1'-chiral centre is presently unknown.

Adult↗

PubMed1993

Simultaneous determination of allopurinol and oxipurinol in human plasma and urine by high-performance liquid chromatography.

The uricostatic drug allopurinol (CAS 315-30-0) is used for treatment of hyperuricaemia and is mainly bio-transformed to the active metabolite oxipurinol (CAS 2465-59-0) in humans. A new assay was developed for the simultaneous determination of both compounds in plasma and urine using ultrafiltration and ion exchange purification steps for plasma and urine, respectively. Reversed-phase high-performance liquid chromatography with ultraviolet detection was applied for the separation and quantitation of both compounds. The limit of detection was 0.1 microgram/ml for both compounds in plasma and 0.2 and 0.5 microgram/ml for allopurinol and oxipurinol, respectively, in urine. Within-run and day-to-day precision of 3-5% and 5-7% was determined for plasma and 6-8% and 8-10% for urine analysis. The assays were further validated using liquid chromatography with photodiode array detection and by comparison with methods using protein precipitation as the purifying step. The high analytical recoveries, selectivity, sensitivity, accuracy and reproducibility were adequate for the measurement of both compounds in pharmacokinetic studies and for drug monitoring in patients on allopurinol therapy.

Adult↗

PubMed1993

Improved identification of Staphylococcus aureus using a new agglutination test. Results of an international study.

A new reagent for the identification of Staphylococcus aureus, SLIDEX STAPH-KIT, operates on the principle of a latex and red blood cell combination agglutination: red blood cells are coated with fibrinogen for the detection of clumping factor, and latex particles are sensitized with anti-S. aureus serotype 18 monoclonal antibody for the detection of protein A and antigen 18. French strains belonging to serotype 18 are methicillin-resistant. The performance of this reagent was compared with STAPHYSLIDE and STAPHAUREX in Europe (France, Germany, Italy), in the United States and in Japan using 548 methicillin-resistant S. aureus strains, 392 methicillin-sensitive S. aureus strains, and 441 non-aureus staphylococci. The specificity of the three reagents was equivalent (98.8% for SLIDEX STAPH-KIT, 99.1% for STAPHYSLIDE, 98.1% for STAPHAUREX). SLIDEX STAPH-KIT (97.3%) was more sensitive than STAPHYSLIDE (93.5%) and STAPHAUREX (89.7%) for all S. aureus strains due to a higher rate of identified methicillin-resistant S. aureus strains.

Agglutination Tests↗

PubMed1993

Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease.

In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease.

Adult↗

PubMed1992

[Incidence, frequency and resistance characteristics of methicillin-oxacillin resistant Staphylococcus aureus strains in Germany].

In a multicentre study, the methicillin-resistant Staphylococcus aureus (MRSA) isolates in 19 large clinics in Germany were recorded, and the resistance characteristics of these strains were studied. Oxacillin-mannitol-salt agar plates were distributed to all participants to ensure uniformity of screening, and each laboratory used these plates to investigate 200 consecutive Staphylococcus aureus isolates for oxacillin-methicillin resistance. Of the 3,794 evaluable Staphylococcus aureus isolates, 71.5% were penicillin and 3.7% (142) oxacillin resistant; four study centres reported methicillin-oxacillin resistance rates of more than 5%. Of the MRSA isolates, 75% were also resistant to ciprofloxacin, 61% to fosfomycin, 52% to imipenem, 50% to trimethoprim/sulfamethoxazole and 36% to clindamycin. All isolates were sensitive to vancomycin and teicoplanin. Of the Staphylococcus aureus strains isolated from patients in intensive therapy units, 10.4% were methicillin-oxacillin resistant. Drains and catheter tips (9.8% and 5.2% respectively) were the materials with the highest proportions of MRSA. Of the MRSA isolates in this study, 58.2% belonged to lysis group II.

Ciprofloxacin↗

PubMed1992

Differences in the interconversion between 20- and 22-carbon (n - 3) and (n - 6) polyunsaturated fatty acids in rat liver.

When male weanling rats were fed diets containing either 5% corn oil or a diet in which half of the corn oil was replaced by fish oil, the 20:5(n - 3) in liver choline and ethanolamine phosphoglycerides, not only partially replaced arachidonate but also paired with palmitic and stearic acids in the same molar ratio as did arachidonate. The 22:5(n - 3)/22:6(n - 3) ratio in the liver phospholipids of corn oil fed rats was similar to that found when the esterified levels of these two acids were increased 5-fold by feeding fish oil. Moreover, the pairing of both 22:5(n - 3) and 22:6(n - 3) with palmitic and stearic acids, on a molar ratio basis, was relatively independent of the total amount of esterified 22:5(n - 3) and 22:6(n - 3). When (3-14C)-labeled 22:4(n - 6) was injected into rats raised on a chow diet or incubated with hepatocytes from these animals, its primary metabolic fate was retroconversion to arachidonate followed by esterification. Conversely, [3-14C]22:5(n - 3) was a poorer substrate for retroconversion with a larger amount being esterified directly into phospholipids and, in addition, this acid served as a precursor for 22:6(n - 3). The enhanced metabolism of both [3-14C]22:4(n - 6) to 22:5(n - 6) and of [3-14C]22:5(n - 3) to 22:6(n - 3) in animals raised on a diet devoid of fat or in their hepatocytes may possibly be due to elevated 6-desaturase activity and/or the level of this enzyme or enzymes. This hypothesis is based on studies showing that the synthesis of 22:6(n - 3) proceeds via a pathway independent of a 4-desaturase but requires the use of a 6-desaturase at two steps (Voss, A., Reinhart, M., Sankarappa, S. and Sprecher, H. (1991) J. Biol. Chem. 266, 19995-20000).

Animals↗