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Biomedical subjects

M Lange

Publications and source records attributed to M Lange.

At least 19 recordsLinked to original sources

Modelling effect of physical and chemical parameters on heat inactivation kinetics of hepatitis A virus in a fruit model system.

While thermal destruction of pathogenic bacteria has been thoroughly studied in food industry, heat inactivation of viruses in food has been poorly investigated. Experiments were carried out to characterize the effects of controlled physical and chemical characteristics of a food matrix upon heat resistance parameters (D and z values) of hepatitis A virus (HAV), taken as model because of its reported heat resistance. Sucrose content (28-52 degrees Brix), calcium concentration (90-1700 mg kg(-1)) and pH (3.3-4.3) were selected for possible influence on thermal inactivation of HAV in strawberry mashes and thus included in an experimental design according to a Doehlert matrix. Use of this design not only allowed to detect and quantify the direct influence of sucrose concentration upon the D85 degrees C value to be higher than the one of pH, but also to reveal a sucrose concentration/pH specific interaction, while no effect of calcium concentration was evidenced. Although the model cannot be directly used to predict heat resistance in real fruit systems, because of differences observed between predicted and measured D85 degrees C values, it is useful for predicting the trends and relative changes in D values due to sucrose concentration and pH variations. Results suggested possible effects of other constituents of strawberry products on heat resistance of HAV and confirmed the importance of experimental validation of any model-derived process. Nevertheless, such a modelling approach using response surface methodology provides a rapid answer to heat resistance evaluation of a food-borne virus as a function of specific physical and chemical parameters of specific food products.

Calcium↗

[Health telematics/telemedicine in the republic of Estonia].

The people of Estonia, who until their independence had been systematically deprived of all forms of information, have shown a ready acceptance of the use of information technology in all areas of life. This environment and an excellent IT infrastructure have since the beginning of the new century provided favourable conditions for developing various individual projects in telemedicine. At the core of current telemedical applications in Estonia is the BITNET Project (in neurology, general medicine), built up with Swedish cooperation, and three German-Estonian projects (in telecardiology and telepathology). These projects are accompanied by studies of their cost-effectiveness. They constitute the basis for the plan that routine telemedical services be taken over by the Estonian health insurance. Differing from the situation in the Scandinavian countries, which have had an effective national telemedical service for over ten years, the special feature of telematrics in Estonia is its international networking with foreign centres of excellence. This has its origin in the aim of Estonian health policy to ensure medical services within its own country in all branches of medicine.

Cost-Benefit Analysis↗

Validating the use of green fluorescent-marked Escherichia coli O157:H7 for assessing the organism behaviour in foods.

AIMS: Monitoring bacterial kinetics in food is of great importance in food safety. The targeted micro-organism has to be identified accurately among competitive flora. Using green fluorescent protein (GFP)-transformed strains is a possible answer to such issues. However, quantitative studies require that this transformation does not alter the micro-organism behaviour: parent and transformed organisms were thus compared. METHODS AND RESULTS: Three Escherichia coli O157:H7 strains were transformed using a GFP-plasmid expressing. Parent and transformed strains were compared according to their genetic characteristics and serotypes. Growth ability was also assessed in constant and fluctuating temperature profiles. Cardinal values of pH, water activity and temperature were computed. No differences were observed between parent and transformed strains for all these experiments. The plasmid was satisfactorily maintained within transformed strains throughout the studies. Growth was eventually monitored in beef meat. CONCLUSIONS: Using the GFP marker is of great value, as it allows easier enumeration of E. coli O157:H7 in food in the presence of natural microflora. Using transformed strains is legitimate: their behaviour does not differ from that of their parent strains. SIGNIFICANCE AND IMPACT OF THE STUDY: GFP transformation appears to be a valuable and reliable tool for challenge testing studies and predictive microbiology.

Animals↗

Evidence for subthermal rotational populations in stored molecular ions through state-dependent dissociative recombination.

We demonstrate that the dissociative recombination of D2H+ with low-energy electrons depends on the rotational energy of the molecular ion such that highly excited ions have a larger rate coefficient than colder ones. Observations on an ion beam continuously interacting with electrons at low relative velocity indicate that excited rotational levels are preferentially depleted which, in competition with radiative heating due to blackbody radiation, provides an opportunity for controlling the rotational temperature of stored molecules.

Journal Article↗

Symmetry locking and commensurate vortex domain formation in periodic pinning arrays.

The spontaneous formation of domains of commensurate vortex patterns near rational fractional matching fields of a periodic pinning array has been investigated with high resolution scanning Hall probe microscopy. We show that domain formation is promoted due to the efficient incorporation of mismatched excess vortices and vacancies at the corners of domain walls, which outweighs the energetic cost of creating them. Molecular dynamics simulations with a generic pinning potential reveal that domains are formed only when vortex-vortex interactions are long range.

Journal Article↗

Growths kinetics comparison of clinical and seafood Listeria monocytogenes isolates in acid and osmotic environment.

Comparison of pathogenic bacterial strains of clinical origin with strains of the same species isolated from the environment may be a valuable tool for microbial risk assessment, especially for foodborne pathogens. Thus, a number of Listeria monocytogenes strains responsible for human cases of listeriosis, in relation to the consumption of contaminated seafood, have been compared with "natural" L. monocytogenes strains isolated from similar seafood products. Complete factorial designs were used to assess quantitatively the growth abilities of four clinical and four seafood isolates of L. monocytogenes placed in various environmental conditions. The cells were submitted to acid and osmotic stress as they were in stationary phase (constant condition) or in exponential phase (dynamic condition). The effects and interactions of pH (5-7) and NaCl concentration (0.5-8% v/v) were studied at two growth temperatures (10 and 20 degrees C). Growth parameters (lag and generation times calculated with Gompertz equation) were used to compare the behavior of the strains with respect to the conditions of culture. The results indicated an overall weak effect of acid stress alone, whereas osmotic stress clearly affected bacterial growth and a synergic effect between these two factors was observed. Clinical strains displayed better adaptation than seafood strains in stationary phase, however, this difference was not verified in exponential phase. Low temperature (10 degrees C) usually confirmed the observations at 20 degrees C, and the differences between clinical and food strains were more pronounced. Finally, a classification of the eight strains, based on the collected data, showed three groups: (i) seafood strains, (ii) three clinical strains and (iii) the last clinical strain, alone due to its high resistance to adverse conditions.

Food Contamination↗

Detection of somatic phages, infectious enteroviruses and enterovirus genomes as indicators of human enteric viral pollution in surface water.

In the present study, we aimed to determine whether the concentrations of somatic coliphages, infectious enteroviruses or the detection of enterovirus genomes were associated with the detection of human pathogenic viruses in surface water. Four French rivers were sampled monthly or semimonthly for the quantitative detection of somatic coliphages, infectious enteroviruses and the qualitative RT-PCR detection of enterovirus, hepatitis A virus, Norwalk I viruses, Norwalk II viruses, astrovirus and rotavirus genomes over 12 months. All the 68 water samples tested were positive for the quantitative detection of somatic coliphages (range of concentrations: 4 x 10(2) to 1.6 x10(5) FUl(-1)). Infectious enteroviruses were isolated by a cell culture system in only two (3%) of the 68 concentrated water samples tested, whereas enterovirus genomes were detectable in 60 (88%) of the same samples. A positive RT-PCR detection of the genome of hepatitis A virus, Norwalk-like virus genogroup II, astrovirus, rotavirus and Norwalk-like virus genogroup I was demonstrated, respectively, in 1.5% (1/68), 1.5% (1/68), 3% (2/68), 0% and 0% of the 68 concentrated water samples tested. All of these four water samples were positive for the detection of enterovirus genomes, whereas only one of them was positive for the isolation of enteroviruses on cell culture. Moreover, the genomic detection of human pathogenic viruses appeared not to be statistically associated with the concentration levels of somatic coliphages in the 68 concentrated water samples tested (Wilcoxon rank test; P=0.14). Taken together, our findings indicate that the quantitative detection of somatic coliphages and the isolation of enteroviruses on cell culture are not suitable parameters for the control of the viral contamination in surface water, whereas the detection of enterovirus genomes may be useful for predicting the presence of waterborne viruses.

Cell Culture Techniques↗

Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation.

The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA-4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations in the amino acid sequences, except for one polymorphism in the leader sequence of CTLA-4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G-insert and two repeat regions in intron 4, consistent with the [T]n and the [GT]n regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of approximately 3500 bp of the upstream region of ICOS revealed an additional eight SNP of which two resided in putative NF-kB and Sp1 sites. In accordance with previous studies we detected no variations in the coding regions except for a rare polymorphism that was found in one donor in the last codon of exon 5, which lead to a heterozygous genotype, but no amino acid change. This suggests that regulation of transcription rather than protein structure could be a possible mechanism in the explanation of linkage.

5' Flanking Region↗

Detection of cutaneous herpes simplex virus infections by immunofluorescence vs. PCR.

BACKGROUND: Detection of cutaneous infections with herpes simplex virus (HSV) has proven difficult, as serum antibody tests sometimes are not sensitive and specific enough for that purpose. OBJECTIVE: This study was conducted to compare the sensitivity for detection of HSV of an immunofluorescence method (Syva Microtrak) and an internally controlled PCR. METHODS: Cutaneous swabs from skin lesions were analysed by immunofluorescence separately for HSV types 1 and 2 and by competitive PCR. Detection of PCR products was done by ELISA, if positive additionally by agarose gel electrophoresis. RESULTS: Of 79 samples 34 were PCR-positive by ELISA (34 = 100%), of which 23 (68%) were also positive on the agarose gel. Eleven samples (32%) were positive by immunofluorescence. No sample was positive by immunofluorescence and negative by PCR. CONCLUSIONS: These results demonstrate that immunofluorescence using Syva Microtrak is not suitable for exclusion of herpes simplex virus infection as sensitivity was only 32%. However, as immunofluorescence is cheaper and faster than PCR, first screening can be done with immunofluorescence, and negative samples can be investigated by PCR to finally prove or exclude the presence of HSV DNA.

Base Sequence↗

Assessment of the hypothalamo-pituitary-adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumor.

The impact of cranial irradiation (CIR) and chemotherapy on the hypothalamo-pituitary (HP)-adrenal (HPA) axis was assessed in a population-based follow-up study of patients treated for childhood brain tumor not directly involving the HP axis. HPA function was evaluated and compared with that in healthy controls (n = 17), measuring basal cortisol and the peak cortisol response to an insulin tolerance test (ITT) and an ACTH test(.) The cortisol cut-off level was 500 nmol/liter. The biological effective dose (BED) of radiotherapy was determined for the HP region and spine and was expressed in Gray units, as BED gives a means of expressing the biological effects of different dosage schedules in a uniform way. Seventy-three children (46 males and 27 females), less than 15 yr of age when diagnosed during 1970-1997 in the Eastern part of Denmark, were included. The median age at time of radiotherapy was 8.4 yr (range, 0.8-14.9). The median length of follow-up was 15 yr (range, 2-29). Fourteen patients (19%) had basal cortisol levels below 500 nmol/liter and did not respond with a peak cortisol above the cut-off level to either an ACTH test (30 or 60 min) or an ITT, and thus, they had insufficiency of the HPA axis. Even though a peak cortisol above 500 nmol/liter was reached in the rest of the cohort (n = 59) after either an ACTH test (30 or 60 min) or an ITT, they had significantly lower peak cortisol levels compared with controls (P = 0.0099). Thirteen patients failed the ACTH test (30 min), but passed the ACTH test (60 min), implying a risk of misinterpreting the cortisol capacity of the patient if only the ACTH test (30 min) is obtained. The basal cortisol levels and the cortisol levels in the ACTH test (30 min) and the ACTH test (60 min) were significantly lower in the patient group compared with controls. There was a significant correlation between the peak cortisol after the ITT compared with the peak cortisol after the ACTH test (30 or 60 min; r(s) = 0.56; P = 0.0006), but 48% failed the ITT, and there was discordance in 10 of 33 (30%) patients who passed the ACTH but failed the ITT, indicating the recommendation of continuous use of the ITT as the gold standard for evaluation of the HPA axis. Stepwise backward multiple linear regression analysis showed that the best-fit model to predict the peak cortisol level after an ITT included BED (P = 0.04) and length of follow-up (P = 0.06). In contrast, age at RT, chemotherapy, BED to the spine, and gender were not included in the model. In conclusion, these data suggest that CIR for a childhood brain tumor may affect the HPA axis, resulting in secondary adrenal insufficiency, whereas adjuvant chemotherapy does not seem to add to the deleterious effect of CIR. We recommend life-long surveillance of the HPA axis and performing regular ITTs.

Adolescent↗

[Necessary prerequisites for the function of an oncological competence center. Information technology, documentation of findings and telecommunication].

INTRODUCTION: The organisation of an interdisciplinary cancer center, especially the establishment of a daily tumorboard requires adequate hardware and intelligent software, which is not available in most hospitals and described here with concepts, realisation and first clinical results. MATERIALS AND METHODS: Based on a TCP/IP network and several inhomogeneous department subsystems we developed an intranet-based oncological documentation- and conference software (oncofile), which can be easily operated and administered in a web browser. Common digital media can be imported and the concept allows for paperless organisation of the daily tumor board. The expert decisions are documented online during tumor board runtime together with selected clinical images and the consensus of the decisionmakers. Local therapeutic guidelines as well as trial information can be accessed over the intranet, and interfaces for internet- and telecommunication are used for second opinion and integration of external expertise. RESULTS: Between 10/99 and 2/2002 3298 presentations of 2438 cases were made in the daily tumor board. 74% of the patients had a curative oncological treatment concept, and 24% of the patients received neoadjuvant treatment. 49% of the patients were scheduled for primary resection. Six patients can be effectively handled in a 30 minute tumorboard. CONCLUSION: The establishment of a daily tumorboard is possible by help of intranet-technology, a central database with web clients and moderate hardware investments. The composition of the patient cohort as well as all decisions ever made to a particular patient are transparent at all times. Prospective quality control studies are under way.

Cancer Care Facilities↗

Modelling microbial growth in structured foods: towards a unified approach.

Historically, the ability of foods to support the growth of spoilage organisms and food-borne pathogens has been assessed by inoculating a food with an organism of interest, and following its growth over a period of time. Information gained from such challenge tests, together with knowledge of the organoleptic stability of the product, can then be used to determine an appropriate shelf-life for the food. Whilst this approach may be seen as the "gold-standard" of microbiological assessment of food, it is both time-consuming and costly. A major advance to complement challenge testing was the development of predictive modelling, when it was demonstrated that the growth of a wide range of organisms of interest could be quite accurately modelled as a function of only a few environmental parameters-primarily temperature, pH and water activity (a(w)), with perhaps other factors such as nitrite, organic acids and oxygen. This approach to predictive microbiology is embodied in software tools such as the UK Food MicroModel and the Pathogen Modeling Program from the USA. Whilst modelling of this form yields accurate predictions of the growth of organisms in the majority of foods, there are occasions when there are discrepancies between the model and the observed growth. These discrepancies are most often described as "fail-safe", i.e. the observed growth is slower than predicted by the model. This paper examines the role of food structure in the development of microbial populations and communities, and describes the methodologies we propose to begin to tackle some of these complex and interlinked issues.

Bacteria↗

Varicella zoster viraemia during herpes zoster is not associated with neoplasia.

BACKGROUND: Shingles are caused by an endogenous or exogenous reinfection with varicella zoster virus (VZV). Up to 50% of individuals with Hodgkin's disease develop herpes zoster; however, no association could be shown between the occurrence of herpes zoster and underlying subclinical malignancies. OBJECTIVE: This study was conducted to investigate whether VZV DNA could be detected by polymerase chain reaction (PCR) in the blood of herpes zoster patients and whether there was an association between VZV viraemia and previous or concurrent neoplasias. METHODS: At least five blood samples from 28 patients with herpes zoster were investigated by internally controlled PCR enzyme-linked immunosorbent assay prior to and during therapy with aciclovir. RESULTS: None of 13 patients, two with a history of neoplasia and two with a neoplasia at the time of the study, showed any signs of viraemia with VZV, and 14 patients had inconsistent viraemia, one with a history of neoplasia and two with neoplasia at the time of the study. In one patient VZV DNA was detected in the blood for 6 days. This patient died soon after from metastatic malignant melanoma. CONCLUSIONS: VZV viraemia may occur during herpes zoster episodes, even in patients without evidence of immunosuppression; however, this viraemia is, in most cases, inconsistent and does not provide any specific information concerning underlying unrecognized malignancies.

Acyclovir↗

The role of endothelins in the regulation of pituitary function.

The different members of the endothelin peptide family exhibit potent, long-lasting vasoconstrictive effects and thus play a central role in blood pressure regulation. However, endothelins have also been shown to modulate renal, cardiac and immune functions under physiological and pathophysiological conditions. In addition, endothelins are thought to be involved in the progression of some types of tumours. Soon after their discovery in 1988, it was shown that endothelins affect hormone release in the pituitary. Moreover, the intrapituitary production and expression of both endothelins and endothelin receptors have been described. This review summarises the present day knowledge concerning the expression and regulation of intrapituitary endothelins and their receptors. In addition, the effects of endothelins on hormone production by anterior, intermediate and posterior pituitary cell types are reviewed and their importance for pituitary physiology and pathophysiology is discussed.

Animals↗

[The physical examination within the scope of The Child and Adolescent Health Survey].

The National Health Survey for Children and Adolescents intends a comprehensive description of the health status of children and adolescents. In this context physical examination of children and adolescents permits collection of objective data concerning physical development, certain body functions and selected performance parameters. Most important are indicators pointing towards increasing developmental and health problems in children and adolescents, which are partly predictive for the health status as an adult. Body measurements including stages of puberty will be taken, the blood pressure measured, vision tests carried out, coordination skills and endurance tested. Besides, if acute symptoms are detected, severity of atopic dermatitis is recorded. The methods and instruments have been tested in a pilot study over a period of one year and were optimised for the main study.

Adolescent↗

[Pilot study of The National Child and Adolescent Health Survey: sampling design].

The concept of a nation-wide Health Survey for Children and Adolescents has been tested over one year in a pilot study with 1,630 participating children and adolescents. A major methodological aspect of this pilot phase was to compare different variants of study sample recruitment regarding their feasibility. There was a choice between a sample originating from the population registry and a cluster sample of schools and school classes for the age group from 11 to 15 years. As a result, after weighing the advantages and disadvantages of both sampling designs, a continuous population registry sample has been recommended. The acquired knowledge and experience will be translated into reality in 2003 when the main course of the survey, which will include about 18,000 children and adolescents, will start.

Adolescent↗

Effect of bupivacaine application on cholinesterase activities, total protein- and albumin concentration in serum and cerebrospinal fluid.

The rationale of this study was to determine whether Bupivacaine used for spinal anesthesia alters the specific secretory activity of nerve cells and/or the function of the blood/cerebrospinal fluid barrier. Four groups were assessed: (1) patients undergoing spinal anesthesia using Bupivacaine for lower limb surgery, (2) spinal Bupivacaine anesthesia without subsequent surgery, (3) local facet joint infiltration using Bupivacaine, and (4) general anesthesia for lower limb surgery without Bupivacaine application. Cholinesterase activities, total protein- and albumin concentrations in serum as well as in cerebrospinal fluid were significantly decreased after surgical intervention under spinal Bupivacaine anesthesia but remained unchanged following spinal Bupivacaine application without surgery. No significant correlation was found between Bupivacaine dosage and parameter alteration. There was no influence of intrathecal Bupivacaine application on the albumin ratio cerebrospinal fluid/serum, nor was there any significant alteration of total protein- or albumin concentrations and butyrylcholinesterase activity in the serum as a result of local injection of Bupivacaine to facet joints. These serum parameters were reduced after surgery under general anesthesia. Alterations of serum- and cerebrospinal fluid parameters investigated after surgery are not related to Bupivacaine application but to effects linked to operative treatment, i.e. suppressed secretory cell activity or protein depletion owing to blood loss. We conclude that the secretory function of cholinesterase-releasing nerve cells is not affected by spinal application of Bupivacaine. The blood/cerebrospinal fluid barrier remains intact.

Aged↗