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Biomedical subjects

A Voss

Publications and source records attributed to A Voss.

At least 145 records · Page 8Linked to original sources

Use of interrepeat PCR fingerprinting to investigate an Acinetobacter baumannii outbreak in an intensive care unit.

An epidemiological investigation of an outbreak of Acinetobacter baumannii among patients on 2 closely related intensive care units (ICU) was performed by molecular typing with interrepeat polymerase chain reaction (interrepeat PCR). 31 A. baumannii isolates obtained from 15 ICU patients were characterized. All patients were infected or colonized with A. baumannii. After identification of the outbreak, 6 environmental isolates were collected from tap-water, sinks and cleaning detergents. PCR fingerprinting identified 3 genotypes among the outbreak-related strains. One predominant genotype was demonstrated in 14/15 patients and this genotype was also found among all environmental isolates. The cluster of A. baumannii represented an outbreak of 1 genotype, suggesting cross-contamination. The finding of the identical genotype among all environmental strains indicated a common environmental source causing the outbreak. The outbreak was controlled after reimplementation of an effective disinfection of workplace surfaces. This survey proved interrepeat PCR to be a rapid and reliable method to differentiate A. baumannii strains, thereby allowing epidemiological surveillance of large amounts of strains and early interventions to control outbreaks.

Acinetobacter↗

Modification of activation-dependent platelet antigens CD62p and CD63 during haemodialysis.

In particular, activated platelets are thought to be involved in the pathophysiology of thrombotic occlusions of vessels. In this study, we evaluated activation-dependent changes in platelet antigens during extracorporeal haemodialysis treatment. Flow cytometry was used in combination with monoclonal antibodies that bind to platelet glycoproteins CD62p (GMP-140) and CD63 (GP53). Maximum peaks of mean channel fluorescence intensity (MCFI) were reached after 60 min in 20/26 procedures in CD62p (P < 0.005) and in 15/25 treatments in CD63 (p < 0.002), respectively. An initial peak of CD62p and CD63 fluorescence expression could be detected in 21/25 and 23/25 treatments, respectively (CD62p within 15, CD63 within 30 min), indicating the early onset of activation. The structural antigen CD41a MCFI slightly decreased over time in all treatments, while CD42b expression did not change. From these results we conclude that haemodialysis contributes to platelet activation and secondary hypercoagulability. Analysis of platelet glycoproteins by flow cytometry may provide clinical information on patients at a higher risk for thrombosis and may help in further improvement of haemodialysis equipment.

Adult↗

[The cytotoxic activity in intestinal lamina propria and peripheral blood in AIDS and Crohn disease].

In this study the cytotoxic activity of natural killer cells (NK) and lymphokine activated killer cells (LAK) in the peripheral blood was examined in ten patients with AIDS and in ten patients with Crohn's disease. The results were compared to the values of ten healthy patients. Cells of the lamina propria of the colon were isolated and cultivated to LAK-cells after the in vitro stimulation with interleukin-2 from patients belonging to these three groups. The highest NK-activity of the monoclonal cells in the peripheral blood (PBMC) was found in the control group. In patients with AIDS and Crohn's disease the activity of the LAK-cells of PBMC was significantly higher than the activity of the NK-cells. The PBMC activity of NK- and LAK-cells in the control group showed no important differences. The spontaneous cytotoxic activity of mononuclear lamina propria cells was very low or not verifiable. In lamina propria LAK-cells only a very low cytotoxic activity was found too. These results show that an in vitro stimulation of PBMC with interleukin-2 in patients with AIDS or Crohn's disease lead to a significant increase of the cytotoxic cell activity.

Acquired Immunodeficiency Syndrome↗

The application of methods of non-linear dynamics for the improved and predictive recognition of patients threatened by sudden cardiac death.

OBJECTIVES: This study introduces new methods of non-linear dynamics (NLD) and compares these with traditional methods of heart rate variability (HRV) and high resolution ECG (HRECG) analysis in order to improve the reliability of high risk stratification. METHODS: Simultaneous 30 min high resolution ECG's and long-term ECG's were recorded from 26 cardiac patients after myocardial infarction (MI). They were divided into two groups depending upon the electrical risk, a low risk group (group 2, n = 10) and a high risk group (group 3, n = 16). The control group consisted of 35 healthy persons (group 1). From these electrocardiograms we extracted standard measures in time and frequency domain as well as measures from the new non-linear methods of symbolic dynamics and renormalized entropy. RESULTS: Applying discriminant function techniques on HRV analysis the parameters of non-linear dynamics led to an acceptable differentiation between healthy persons and high risk patients of 96%. The time domain and frequency domain parameters were successful in less than 90%. The combination of parameters from all domains and a stepwise discriminant function separated these groups completely (100%). Use of this discriminant function classified three patients with apparently low (no) risk into the same cluster as high risk patients. The combination of the HRECG and HRV analysis showed the same individual clustering but increased the positive value of separation. CONCLUSIONS: The methods of NLD describe complex rhythm fluctuations and separate structures of non-linear behavior in the heart rate time series more successfully than classical methods of time and frequency domains. This leads to an improved discrimination between a normal (healthy persons) and an abnormal (high risk patients) type of heart beat generation. Some patients with an unknown risk exhibit similar patterns to high risk patients and this suggests a hidden high risk. The methods of symbolic dynamics and renormalized entropy were particularly useful measures for classifying the dynamics of HRV.

Death, Sudden, Cardiac↗

Uric acid lowering effect of oxipurinol sodium in hyperuricemic patients - therapeutic equivalence to allopurinol.

OBJECTIVE: Oxipurinol has been shown to be sufficiently absorbed after oral administration as a rapid release preparation of oxipurinol sodium. We compared the uric acid lowering affect of allopurinol and oxipurinol. METHODS: In a multicenter, randomized, double blind crossover trial in 99 hyperuricemic patients with normal renal function we investigated the uric acid lowering effect of oxipurinol sodium (O) in daily amounts equimolar to 300 mg allopurinol (A). Mean pretreatment plasma uric acid concentrations in groups A/O and O/A were 8.3 +/- 1.4 and 8.7 + /- 1.4 mg/dl, respectively. RESULTS: In group A/O the mean plasma uric acid decreased to 5.4 +/- 1.2 mg/dl with allopurinol treatment, and increased slightly to 5.7 + /- 1.3 mg/dl during the consecutive oxipurinol period. In group O/A plasma uric acid declined to 6.0 +/- 1.4 mg/dl with oxipurinol and was 5.6 + /- 1.3 mg/dl at the end of the allopurinol period. The overall average reduction compared to baseline was 3.0 mg/dl with allopurinol and 2.6 mg/dl with oxipurinol. The difference between the 2 treatments was small but significant (multiple p=0.027,2 tailed). The corresponding mean plasma oxipurinol concentrations were 9.24 mu g/dl at the end of the allopurinol period and 9.9 mu g/dl after treatment with oxipurinol (NS). CONCLUSION: Oxipurinol is well absorbed and sufficiently effective in hyperuricemic patients when administered as a rapid release preparation of oxipurinol sodium. Oxipurinol sodium could be a substitute for allopurinol in hyperuricemic patients and possibly also with new uses for allopurinol.

Adult↗

Different risk groups in node-negative breast cancer: prognostic value of cytophotometrically assessed DNA, morphometry and texture.

Feulgen-stained imprints and fine-needle aspirates from 528 lymph-node-negative breast cancers were investigated by means of an image analysis system. Several DNA, morphometric and textural parameters were evaluated for each patient. The prognostic value of the parameters was investigated by multivariate Cox regression analysis. As prognostic criteria, a distant recurrence-free survival of 5 years and an overall survival of 8 years were considered. In multivariate analyses the anisokaryosis (standard deviation of nuclear radius, Rad-SD) was the strongest parameter in predicting the clinical course of node-negative patients. This was followed by a textural parameter (run-length, NR2 M) and the tumor size (pT). The DNA histogram type could also add prognostic information concerning distant recurrence-free survival, but not overall survival. In both approaches a multivariate prognostic factor was calculated for each of the node-negative patients by a linear combination of the selected variables. Using this factor, patients could be split into 5 subgroups with significantly different risks of distant metastases. Thus, a low-risk subgroup, with a 5-year distant recurrence rate of only 3%, and a subgroup with a considerably higher risk and a distant recurrence rate of 35%, could be distinguished. In survival analysis the low-risk group of node-negative patients showed an 8-year death rate of only 3%, whereas in the high-risk group 30% of the patients had died at 8 years. Thus DNA, morphometric and textural parameters can provide powerful prognostic information in node-negative breast carcinomas. The multivariate combination of the relevant variables may allow a better selection of those node-negative patients with a proven good prognosis, and of those who are at risk of distant recurrence and therefore may benefit from adjuvant treatment.

Adult↗

Identification of a low-risk group of stage I breast cancer patients by cytometrically assessed DNA and nuclear texture parameters.

Image cytometrical measurements were performed on Feulgen-stained cells from 329 stage I breast cancers (pT1pN0,M0,R0). For each patient, several DNA (ploidy, S-phase fraction, exceeding rates, 2c deviation index, ploidy balance, entropy, and histogram typing), morphometric (area and radius of nuclei), and textural parameters (mainly co-occurrence and run-length) were calculated. The prognostic value of these parameters was investigated by multivariate Cox regression analysis, considering a distant recurrence-free survival of 8 years as the prognostic criterion. In the multivariate analysis, one DNA parameter (histogram type) and two textural parameters (co-occurrence and variation of the average heterochromatin area) were proven to have independent prognostic value. Using a linear combination of these variables, a prognostic factor was calculated for each individual patient. Patients were stratified using this factor into several groups according to their risk for distant recurrence. Thus, a low-risk group of stage I patients was identified, remaining distant recurrence-free for 8 years. In addition, a group of patients with a worse prognosis and an 8-year recurrence rate of about 26 per cent was identified, compared with the average distant recurrence rate of all stage I patients of 13 per cent. A combination of DNA and textural parameters can provide powerful prognostic information in stage I breast carcinomas and may allow a better selection of patients for different therapy protocols.

Adult↗

Disposition and uric acid lowering effect of oxipurinol: comparison of different oxipurinol formulations and allopurinol in healthy individuals.

We have investigated the disposition and plasma uric acid lowering effect of oxipurinol in ten healthy individuals following oral administration of three different formulations of oxipurinol and of allopurinol in equimolar doses. The reduction of plasma uric acid was clearcut up to 48 h. As estimated from plasma AUC0-infinity, Cmax, tmax, tlag, and urinary drug excretion, a conventional rapid release preparation of oxipurinol sodium was clearly superior to oxipurinol as free acid and to enteric coated microtablets of oxipurinol sodium. Plasma oxipurinol concentrations following a single dose of the conventional formulation of oxipurinol sodium were approximately 25% lower than those observed after an equimolar dose (300 mg) of allopurinol, but mean Cmax reached the value reported to be necessary for 90% inhibition of xanthine oxidase. Since prolonged administration will result in accumulation of oxipurinol because of its slow elimination, this type of oxipurinol formulation can be expected to meet the therapeutic requirements for a drug to lower plasma uric acid.

Administration, Oral↗

Improved prognostication in small (pT1) breast cancers by image cytometry.

Feulgen-stained samples from 460 small (pT1) primary breast cancers were investigated by means of an image analysis system. Several DNA, morphometrical and textural parameters were evaluated for each patient, and the prognostic meaning of these parameters was then investigated by the Cox regression analysis. As prognostic criterion a distant recurrence-free survival of five years was considered. All investigated DNA- and morphometrical parameters as well as several textural parameters showed a significant univariate correlation with the clinical course. In a multivariate approach the axillary nodal status was the most important prognostic parameter, followed by a morphometric parameter (anisokaryosis) and two textural parameters (runlength and co-occurrence). None of the DNA histogram derived parameters could add prognostic information in this multivariate approach. By the linear combination of the four selected variables, an individual prognostic factor was calculated. Using this factor the patients could be split into several groups according to their risk for distant metastases. Thus a low risk group of pT1 patients could be identified with a distant recurrence rate of only 2% after 5 years, and also a group of patients with a considerably worse prognosis and a 5-year distant recurrence rate of 53%. In contrast, using the nodal status as single parameter allows the identification of a low risk group of patients (pN0pT1) with a distant recurrence rate of 10.6%. Therefore, morphometrical and textural parameters can provide powerful prognostic information in small breast carcinomas and may allow a better selection of patients for adjuvant therapy.

Aged↗

Improved analysis of heart rate variability by methods of nonlinear dynamics.

The traditional analysis of heart rate variability (HRV) in the time and frequency domains seems to be an independent predictive marker for sudden cardiac death. Because the usual applied methods of HRV analysis describe only linear or strong periodic phenomena, the authors have developed new methods of HRV analysis based on nonlinear dynamics. In that way, parameters are extracted that quantify more complex processes and their complicated relationships. These methods are symbolic dynamics that describes the beat-to-beat dynamics and renormalized entropy that compares the complexity of power spectra on a normalized energy level. In an initial investigation, the HRV of 35 healthy subjects and 39 cardiac patients have been analyzed. Using discriminant functions, the authors found an optimal (100%) differentiation between the group of healthy subjects (even using only an age-matched subgroup of 12 subjects) and that of patients after myocardial infarction with a high electrical risk (Lown 4b). Applying this discriminant function to a group of patients with low electrical risk, four patients show the same behavior indicative of a high risk score, which might be a sign for a hidden high risk, two patients show healthy behavior, and the remaining patients show a separate pattern. The use of new methods of nonlinear dynamics in combination with parameters of the time and frequency domains in HRV offers possibilities for improved classification of HRV behavior. It is suggested that this could lead to a more detailed classification of individual high risk.

Adult↗

Disease-free survival of node-positive breast cancer patients. Improved prognostication by cytometrical parameters.

Feulgen stained cytologic samples from 225 node-positive breast cancers were investigated by means of an image analysis system. From each tumor sample, 100 cells were scanned and several DNA, morphometrical and textural parameters were evaluated. The meaning of the cytometric parameters for prediction of distant metastases within five years was investigated by the stepwise Cox regression analysis. Most of the investigated DNA- and morphometrical parameters, as well as one textural feature, showed a significant univariate correlation with the clinical course. In the multivariate approach, the lymph node status (pN) was the strongest prognostic factor, followed by the histogram type, the tumor size (pT) and a textural parameter (heterochromatin area). By the linear combination of these selected variables a multivariate prognostic factor was calculated for each individual patient. Using this factor, the patients could be splitted into four groups according to their risk for distant metastases. For this, the continuous range of the multivariate factor was subdivided so that about 35% of the patients were in the middle groups and about 15% of the patients in each of the border groups with highest and lowest factors, respectively. Thus a low risk group (lowest factors) of node-positive patients could be identified with a 5-year distant recurrence-rate of only 6.5%, as well as a group of patients with a considerably worse prognosis (highest factors) and a distant recurrence-rate of 67%. Therefore, DNA, morphometrical and textural parameters can provide powerful prognostic information in node-positive breast carcinomas. Using the multivariate combination of clinical and relevant cytometrical parameters may allow a more appropriate selection of patients for adjuvant therapy.

Biopsy, Needle↗

Interrepeat fingerprinting of third-generation cephalosporin-resistant Enterobacter cloacae isolated during an outbreak in a neonatal intensive care unit.

OBJECTIVE: To investigate an outbreak in neonates of Enterobacter cloacae infection resistant to third-generation cephalosporins. DESIGN: A retrospective study of an outbreak in the neonatal intensive care unit (NICU) and review of E cloacae isolates in pediatric wards and other intensive care units from June 1992 through March 1993. SETTING: An academic tertiary care hospital. PATIENTS: Six patients admitted to the NICU were colonized or infected with E cloacae resistant to third-generation cephalosporins. In the period preceding the outbreak, four E cloacae isolates were available from four patients in the pediatric surgical ward. Nine isolates from four patients in two other intensive care units (ICUs) also were collected during the outbreak. Isolates were biotyped by the API 50CH system and genotyped by polymerase chain reaction (PCR) fingerprinting. RESULTS: Typing by interrepeat PCR showed that 21 isolates, which were obtained from five neonates, were identical. One neonate was colonized with a different strain. Some neonates were colonized with a single type of E cloacae for a relatively long period of time. Isolates of patients who were cared for in the pediatric surgical ward and the two other intensive care units (ICUs) showed different genotypes. One patient in an ICU was colonized with an E cloacae strain genetically identical to the outbreak strain. No predominant biotype could be established. CONCLUSIONS: E cloacae can colonize neonates for a long period of time and although colonization with E cloacae initially may arise endogenously, we were able to show further transmission by cross-contamination in a neonatal intensive care unit.

Bacterial Typing Techniques↗

Investigation of Candida albicans transmission in a surgical intensive care unit cluster by using genomic DNA typing methods.

An apparent outbreak of serious Candida albicans infections (n = 6) occurred in a surgical intensive care unit over a 4-week period. Four patients developed C. albicans bloodstream infections. An additional patient developed catheter-related C. albicans infection; the sixth patient developed an infection of cerebrospinal fluid. C. albicans was isolated from the hands of five health care workers (17%) and the throat of one health care worker (3%) during the outbreak investigation. Karyotyping and restriction endonuclease analysis of genomic DNA with BssHII of 23 C. albicans isolates from patients and the 6 health care worker isolates revealed 9 and 12 different patterns, respectively. Three of six patients appeared to be infected with the same C. albicans strain (two bloodstream infections and one cerebrospinal fluid infection). The hands of a health care worker were colonized with strain that appeared identical to an isolate from a patient prior to infection of the patient. However, restriction endonuclease analysis with SfiI found differences among the isolates determined to be identical by the other two methods. Karyotyping alone does not appear to be sufficient to differentiate between outbreak and control isolates. Restriction endonuclease analysis typing may be a more sensitive method than karyotyping alone in the investigation of a cluster of C. albicans infections. Furthermore, the use of more than one restriction enzyme may be necessary for optimal strain discrimination in restriction endonuclease analysis of genomic DNA.

Candida albicans↗

[An optimized filter system for eliminating 50 Hz interference from high resolution ECG].

A 50/60 Hz notch filter system was designed to eliminate powerline interferences from the high-resolution ECG. This special filter causes only minimal distortions of the power spectra and thus permits us to filter high-resolution ECG's without any appreciable changes in the frequency distribution of the original signal. Since the filter is based on an integer coefficient filter technique, the calculation time is relatively short, and the programming effort comparatively low. Three different automatically selected transfer functions ensure that an optimal filtered signal is obtained despite variations in the value of the interference.

Artifacts↗

[Streptococcus B screening with GBS medium in obstetrics].

Pregnant women and newborn infants were screened for group B streptococcal (GBS) colonization by obtaining paired swabs from the cervix and urethra for the former group and from the ear, nose, umbilical cord, gastric juice and membranes for the latter. One swab was cultured on blood agar; the other was inoculated into serum-starch broth (GBS medium), which allows identification of GBS by production of a characteristic orange-colored pigment. From the 2105 paired swabs obtained, a total of 158 were GBS positive by either method; of these, 154 (97.5%) were recovered by the GBS medium and 89 (56.3%) by blood agar plate. No false positive color reactions were observed with GBS medium. 75% of the positive GBS media could be read within 24 h of incubation. The use of GBS medium proved to be an easy and reliable method for screening of maternal and neonatal GBS colonization.

Culture Media↗

[In vitro activity of sparfloxacin against methicillin-resistant staphylococci].

The antimicrobial activity of sparfloxacin (CAS 110871-86-8) against 154 clinical isolates of methicillin-resistant staphylococci was investigated and compared with that of 6 other fluoroquinolones. The isolates consisted of 100 methicillin-resistant Staphylococcus aureus (MRSA), 29 Staphylococcus epidermidis (MRSE) and 25 other coagulase-negative staphylococci (CNS). Sparfloxacin was more active than ciprofloxacin and the other fluoroquinolones against all strains tested. The MIC90 of sparfloxacin against the 100 isolates of Staphylococcus aureus was 8 mg/l, while that of ciprofloxacin was > or = 64 mg/l. Moreover, ciprofloxacin-susceptible MRSA isolates were inhibited by sparfloxacin at a concentration of < or = 0.06 mg/l. The other quinolones had an MIC90 ranging from 0.5 mg/l to 4 mg/l against ciprofloxacin-susceptible MRSA. Similar results were obtained for the MRSE and CNS isolates tested. As many as 90% of the ciprofloxacin-susceptible microorganisms were inhibited at a concentration of < or = 0.06 mg/l or 0.125 mg/l of sparfloxacin. The MIC90 of sparfloxacin against ciprofloxacin-resistant CNS and MRSE were 4 mg/l and 8 mg/l, respectively. Sparfloxacin was clearly more active than any of the other quinolones against all species tested, although higher concentrations were needed to inhibit ciprofloxacin-resistant staphylococci.

Anti-Infective Agents↗

Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. I. Uric acid kinetics.

The interaction of allopurinol (300 mg/day) and hydrochlorothiazide (50 mg/day) was studied in seven healthy male volunteers during prolonged coadministration of the two drugs using defined dietary conditions. A formula diet was administered with the allopurinol throughout the 24-day study, while hydrochlorothiazide was added during days 11-21. After the addition of hydrochlorothiazide both plasma uric acid and plasma oxipurinol rose for 6 days--24% and 30%, respectively, compared to steady-state levels during allopurinol alone (P < 0.01 each). In neither substance were variations in renal excretion significant. By the end of combined treatment (day 21), the changes induced by hydrochlorothiazide had already been reversed to a considerable extent. It is concluded that both in normal individuals and in patients with normal renal clearance of uric acid the effect of hydrochlorothiazide on the plasma concentration and renal excretion of oxipurinol is small. When taking both drugs, there is no increased risk during long-term treatment, and a risk is even questionable during the first days.

Administration, Oral↗