Biomedical subjects

M Daniel

Publications and source records attributed to M Daniel.

At least 73 records · Page 4Linked to original sources

PubMed1998

Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides.

The Salmonellae PhoP-PhoQ virulence regulators induce resistance to host cationic antimicrobial peptides (CAMP) after infection of vertebrate tissues, and Mg2+ or Ca2+ limitation. The PhoP-PhoQ activated gene, pagP, was identified as important to inducible CAMP resistance and increased acylation of lipid A, the major component of the outer leaflet of the outer membrane. pagP mutants demonstrated increased outer membrane permeability in response to CAMP, supporting the hypothesis that increased lipid A acylation is a CAMP resistance mechanism. Similarly, in response to Mg2+ limited growth, other enteric Gram-negative bacteria demonstrated increased lipid A acylation. Compounds that inhibit the ability to increase lipid A acylation may have utility as new antimicrobial agents.

Acylation↗

PubMed1998

Hepatitis C virus genotypes and the influence of the induction of immunosuppression with anti-thymocyte globulin (ATG) on chronic hepatitis in renal graft recipients.

Hepatitis C virus (HCV) exhibits a dramatic genetic variability and several mechanisms of immunological response are unable to control hepatic and extrahepatic replication. Genotype 1 b is associated with more severe clinical manifestations and is less responsive to interferon. In addition, we have reported an increase of HCV RNA viral load after renal transplantation. Anti-thymocyte globulin (ATG) is supposed to increase viral replication and liver dysfunction in chronically infected renal graft recipients. We evaluated the genotype profile in HCV+ patients of our Renal Transplant Unit and studied the effects of ATG, as part of the induction of immunosuppression, on viral load and liver enzymes abnormalities. From 726 renal graft recipients, 104 patients, with a mean follow up of 3.9 +/- 2.9 years, were anti-HCV+ by ELISA II. HCV RNA was measured by quantitative PCR. We correlated the viral load and biochemical liver parameters with genotype, exposure to ATG as induction therapy, early acute rejection episode and the duration of infection. Of the 81 patients tested, 72% were viraemic and genotype 1 b was the predominant viral strain (66%). The majority of these patients (65%) were coinfected by two or more strains. There was no correlation between HCV RNA blood levels and liver enzymes. We did not find higher viral load with genotype 1 b infection (68 +/- 88 mEq/ml vs 75.8 +/- 123 mEq/ml in the others) nor with ATG induction therapy (43.5 +/- 71.3 mEq/ml vs 64.1 +/- 110.5 mEq/ml). Early acute rejection and longer follow up were not associated with higher levels of HCV RNA. The biochemical liver profile showed no relationship with the variables studied. We concluded that genotype 1 b is the predominant strain in our HCV+ population and there is a great prevalence of coinfection with several genotypes. Our results did not confirm a deleterious effect of the use of ATG as induction therapy in these HCV-infected patients. Prospective randomised studies with liver biopsy evaluation are needed to answer more fully the remaining questions about the best immunosuppressive therapy in renal graft recipients with chronic HCV infection.

Genotype↗

PubMed1998

Contact with ticks and awareness of tick-borne diseases among the Czech population--a pilot study.

In the Czech Republic, the incidence of Lyme borreliosis (LB) has shown a rising trend since 1988. The goal of this study has been to find out to what extent a selected part of population is aware of ticks and of the relationship between ticks and LB. The study was based on a questionnaire survey. A total of 110 respondents were selected, including 19 secondary school students, 32 blood donors, 44 park-goers, 15 countryside people. As many as 99% of the respondents were aware of the presence of ticks, 91% knew that ticks are sucking blood of humans and animals, 1.8% thought they eat leaves. 74.5% of the respondents expect ticks to reach them from the vegetation while 22% believe that ticks fall from the trees. Furthermore, 87% and 75% of the respondents indicated to have had ticks attached to the skin or to have removed a tick from other persons' skin, respectively. Only 6.7% of them had never come into contact with ticks. 17% of the respondents use disinfectant when removing a tick, while 67% use oil for tick removal. Almost 30% remove ticks with naked hands. Over 14% destroy the ticks by squashing them with naked fingers. Finally, about 11% of the population studied had never heard about LB and 41% were not aware of the risk of tick-borne encephalitis.

Adolescent↗

PubMed1998

Ixodes ricinus strains in Europe.

An analysis of cuticular hydrocarbons (CH) of unfed adult Ixodes ricinus ticks collected throughout Europe showed that there are 10 distinct I. ricinus groups. Studies on the seasonal and annual consistency of CH composition and possible effects of host and environmental factors suggested that CHs may be used as a genuine genetic marker for I. ricinus. Preliminary studies compared the vector competence of ticks from three of the most separated I. ricinus groups and the results suggested that there may be significant differences in tick susceptibility to Borrelia afzelii.

Animals↗

PubMed1998

Lyme borreliosis habitat assessment.

Tick ecologists throughout Europe provided descriptions of Lyme borreliosis habitats according to a standardised format and data for 105 habitats in 16 countries were received. The data showed that high risk situations, as defined by the presence of large numbers of B. burgdorferi sensu lato-infected nymphal I. ricinus, occur in heterogeneous deciduous woodland, usually with a recreational function and with a diverse fauna, usually including deer. Large numbers of ticks occurred in some other habitats, but infection prevalence was usually low. The situation for adult I. ricinus was similar but less clearly defined. Tick infection rates were found to be lower in western Europe than in the east, and the infection rate in I. persulcatus, the most easterly vector species, was markedly higher than in I. ricinus. In the vast majority of habitats the infection rate in adult I. ricinus was greater than in nymphs. Larvae were rarely found to be infected.

Animals↗

PubMed1998

Lyme borreliosis awareness.

A Lyme borreliosis information leaflet has been produced to promote awareness amongst the general public. It was designed to provide a framework for similar material throughout Europe and complements a questionnaire produced to measure awareness of Lyme borreliosis. This questionnaire can be used to determine the impact of educational campaigns using material such as the leaflet. Feasibility studies showed that the questionnaire successfully highlighted predictable differences between sample groups and also that the leaflet performed well in increasing knowledge in low-awareness groups.

Blood Donors↗

PubMed1998

Predictive map of Ixodes ricinus high-incidence habitats and a tick-borne encephalitis risk assessment using satellite data.

The main objective of this project was to predict Ixodes ricinus abundant habitats reliably as a means of tick-borne encephalitis (TBE) risk assessment for the prevention of this disease. The vegetation types were used as the indicators of an ecosystem suitable for tick occurrence, for TBE virus circulation and, accordingly, for the existence of natural foci of this infection. Remote sensing methods were used to determine the indicative plant cover. Satellite data covering an experimental area of 70 x 70 km in Central Bohemia, the Czech Republic, was acquired by the Landsat 5 TM scanner. Nine forest classes were recognized in the experimental area by successive supervised and unsupervised classifications and identified in a field-checking botanical survey. An epidemiological TBE map based on human cases contracted in the territory under study was exploited for the evaluation of risk in particular forest classes. Predictive maps are expressed both in digital and in printed forms at a scale of 1:300,000 for an overall risk evaluation and at a scale of 1:25,000 for a detailed local orientation.

Animals↗

PubMed1998

Fentanyl augments the blockade of the sympathetic response to incision (MAC-BAR) produced by desflurane and isoflurane: desflurane and isoflurane MAC-BAR without and with fentanyl.

BACKGROUND: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner. METHODS: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group. RESULTS: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P < 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC). CONCLUSIONS: Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.

Adolescent↗

PubMed1998

Group B Streptococcal septicaemia/meningitis in neonates in a Singapore teaching hospital.

Our aims were to establish the incidence and clinical characteristics of early and late onset Group B Streptococcal (GBS) septicaemia in neonates in our hospital over a period of 1 year. Routine screening for maternal GBS was not standard practice in the hospital. GBS was isolated from high vaginal swabs (HVS) obtained antenatally or postnatally for risk factors as determined by the obstetrician or neonatologist in charge. Data obtained were analyzed separately and these did not form part of the study. By a system of clinical case review and follow-up, mail, telephone and home visits, the outcome of all 15,062 livebirths in the hospital over a 1-year period were verified and reported. Our results show a low incidence of GBS infection in neonates in the hospital: early onset disease was 0.265 per 1,000 livebirths and late onset a quarter of that. The majority of our cases of early onset GBS disease were in premature infants. Because of our low incidence, prophylaxis schedules would have to ensure an acceptably smaller number of mothers exposed to antibiotics over and above the current level and the cooperation of our obstetricians. We have devised a schedule incorporating a current PROM (prelabour premature rupture of membranes) protocol which would result in only an additional 2.2% of mothers requiring prophylactic antibiotics.

Age of Onset↗

PubMed1998

Paradigm change and uncertainty about funding of public health research: social and scientific implications.

Since the 1970s two fundamental shifts have occurred in health research funding: a reduction in the buying power of research dollars, and an increase in the competition for resources. Most fields have also seen a decrease in the dollars available for research. Pressures for justifying the relevance of research activities have become increasingly pragmatic. The thesis of this paper is that scientific creativity and innovation are compromised by the highly uncertain and competitive funding environment of contemporary health research. This is largely because criteria of scientific excellence predicated on an investigation's presumed future impact support the status quo of methods and subject matter in funded research. Extraordinary rationality among scientists seeking and allocating resources promotes the survival of the existing system over time, yet inhibits progressive development through the transformation of conceptual models. Therefore, despite a growing unrest about the way research on population health is conducted, new conceptions of the relationship between theory and methods have been slow to emerge. Amelioration of a disjunction between the institutionalized rules governing science and the culturally sanctioned goals of science requires commitment to a dialectic between orthodoxy and dissent.

Creativity↗

PubMed1998

Preclinical development of low toxicity drugs: focus on zanamivir, an anti-influenza drug.

Developing novel compounds with low toxicity may present more difficulties for pharmaceutical companies than developing compounds with known class-related effects. The absence of clearly identified toxicity may be a consequence either of an inadequate or poorly designed toxicity programme or of the very low toxicity of the novel compound. To enable an informed risk assessment to be undertaken prior to registration, regulatory authorities must satisfy themselves that all efforts to fully evaluate the toxicity profile of a novel compound have been made. Zanamivir is a novel antiviral agent developed for the treatment and prevention of influenza when administered by the oral inhaled route. The toxicology programme for zanamivir was designed to support both a short term treatment indication for patients clinically diagnosed with influenza and a longer term treatment indication for the prevention of influenza. The toxicology studies demonstrated that zanamivir has very low toxicity and no drug-specific toxicities were observed in animal toxicity studies. Systemic plasma concentrations 1336-fold those achieved in clinical use were not associated with significant adverse effects. In the absence of dose-limiting toxicity in animal studies and in an attempt to identify target-organ toxicity, the high dosage level in all repeat dose studies was selected to be the maximum practicable. In the rat, nonspecific effects were seen in the respiratory tract following long term inhaled administration and in the kidneys following continuous infusion. However, these nonspecific effects were consequences of the excessive dosages administered and are not related specifically to zanamivir; thus, they are without relevance to the clinical use of this agent.

Administration, Inhalation↗

PubMed1998

[Prediction of sites with an increased risk of infestation with Ixodes ricinus and tick-borne encephalitis infection in the Central Bohemia Region based satellite data].

Based on elaboration of a prediction map of sites of increased incidence of Ixodes ricinus associated with an increased risk of attack on humans and activation of the virus of tick-borne encephalitis it was assumed that different types of vegetation can serve this purpose as suitable indicators. For assessment of these sites and their location on the territory of the Central Bohemian region (on an area of 11,508 sq.km) data from spectral analysis of reflected light recorded by a scanner, Thematic Mapper, working on satellite LANDSAT 5 with a spatial resolution of 30 m, obtained in six bands of the visible and near infrared spectrum resp. was used. Digital satellite data were processed in station IBM RISC 6000 using the professional software EASI/PACE of PCI Co. Inc. Canada. First by supervised classification seven main classes describing the position of the whole area were differentiated and then by a combination of unsupervised and subsequently supervised classification the forest areas were divided into nine classes of forests (with a different structure and different composition as to species), which have a different incidence of ticks. These classes were then compared by statistical methods with the epidemiological map of risk of acquisition of the tick-borne encephalitis virus. This resulted in the finding that coniferous tree forests ("1" and "2") are practically devoid of risk, while mixed and deciduous forests ("3" to "9") involve a varying degree of risk. The maximum risk was found in class 6 which comprises very heterogeneous young deciduous growth and ecotones. The results are presented graphically on the specimen of the prediction map (part of the classified picture supplemented by topographic signs at scale 1:25,000) and on classified satellite picture of the whole area (scale of the original computer printout 1:300,000). In the legend the grade of risk of different classes is expressed verbally, corresponding to values of the Spearman coefficient of rank correlation (Table 1). The laboratory tests were verified and characterized from the botanical aspect during the field investigation.

Animals↗

PubMed1998

[Educational status of the Czech population about Lyme borreliosis and experience with tick bites--pilot study].

The incidence of Lyme borreliosis (LB) has a rising trend since 1995. In 1995 6,302 cases were reported, in 1996 4,192 (EPIDAT, SZU). The objective of the present work was to assess in a selected population sample knowledge of ticks and their relationship to Lyme borreliosis. The investigation was based on a survey using questionnaires. 110 respondents were selected according to the following pattern: 19 secondary school students, 32 blood donors, 44 visitors of parks, 15 countryside people. 99.1% of the subjects knew about the existence of ticks in the Czech Republic, 10.9% of the respondents do not know about Lyme borreliosis. More than 80% of the people are in the countryside at least once a week. 87% of the people report they had a tick, 75% removed a tick from another person. Only 6.7% of the respondents never had any contact with ticks. When removing ticks 17% of the subjects use disinfection, 67% use oil. Almost 30% of the respondents remove ticks with bare hands and more than 14% destroy them by squashing them between their fingers. 41% are not aware of the risk of transmission of tick-borne encephalitis. From the investigation a frequent contact of the population with ticks is apparent. Theoretical knowledge of the problem is extensive, practical experience is different. Unfortunately unsuitable habits in removal of ticks persist and this increases the risk of transmission of Lyme borreliosis.

Adult↗

PubMed1998

Quality of life in young adults having received a BMT during childhood: a GETMON study. Grupo Español de Trasplante de Médula Osea en el Niño.

A quality-of-life questionnaire study was administered in a group of 98 disease-free survivors more than 3 years after BMT. All participants were over the age of 17 years at the time of the survey. The transplants were performed between 1981 and 1993 in eight Spanish hospitals. Eighty-three percent of patients had undergone BMT for neoplastic disease. Seventy-three per cent received an allogeneic bone marrow transplantation. A modified version of a questionnaire applied in Stanford Hospital to evaluate quality of life in adults after BMT was used. A single investigator was responsible for interviewing all subjects by telephone. We compare these results with the same questionnaire applied in a control group of 58 healthy subjects of similar age. The most significant results were: BMT patients valued their quality of life more highly than the control group. The mean score for global quality of life was 8.19+/-0.17 in BMT group as compared to 7.54+/-0.13 in control group (P=0.0013). Studies were cited as the major concern in both groups: 24% in BMT group and in 69% in control group (C.I. 95%=0.59 to 0.30). The patients in the BMT group considered they had fewer problems in comparison with the control group regarding interpersonal relationships with family members and friends, sleep, depression and leisure possibilities. However, they considered they had more problems concerning their physical appearance, studies and work possibilities than their peers. Considerations regarding weight, height, sexual functioning, anxiety, tendency to suffer illness and problems with insurance were similar in both groups.

Adolescent↗

PubMed1998

Fermentation of non-starch polysaccharides in mixed diets and single fibre sources: comparative studies in human subjects and in vitro.

The present study investigated whether the extent of fermentation of NSP in human subjects could be predicted by an in vitro batch system. Fibre sources studied were five mixed diets containing different amounts and types of fibre and three single fibre sources (citrus fibre concentrate, coarse and fine wholemeal rye bread). Fermentation in human subjects was determined in balance experiments in women who were also donors of the faecal inocula. In vitro fermentations were performed with fibre residues prepared from duplicates of the fibre-containing foods consumed during the balance trials. Fermentation of total NSP in vivo was between 65.8 and 88.6% for the mixed diets and 54.4, 58.0 and 96.9% for the coarse and fine wholemeal rye breads and the citrus fibre concentrate respectively. For the mixed diets and the citrus fibre concentrate, mean differences between the extent of NSP degradation after 24 h in vitro incubation and that in vivo were between -0.7 and 5.0%. Differences were significant for one diet (P < 0.05). For the wholemeal rye breads, the fermentation in vitro exceeded that in vivo significantly, but the magnitude of the difference in each case was small and without physiological importance. Particle size of breads had no influence on the extent of NSP degradation. These results indicate that the in vitro batch system used could provide quantitative data on the fermentation in vivo of NSP in mixed diets and some single fibre sources. An in vitro incubation time of 24 h was sufficient to mimic the NSP degradation in vivo.

Adult↗

PubMed1997

CADIAG-2 and MYCIN-like systems.

CADIAG-2 and MYCIN-like systems are expert systems with numerous applications in medicine. CADIAG-2 is a fuzzy expert system based on max-min inference, while MYCIN-like systems use combining functions to calculate the global weights (degrees) of suggested diagnoses. This paper brings a comparison of CADIAG-2 and MYCIN-like systems. It studies relations between them and shows how CADIAG-2 can be embedded into MYCIN-like systems. An approach of inclusion of negative knowledge into CADIAG-2 is proposed. Some remarks regarding the acquisition of weights of rules are given as well.

Expert Systems↗

PubMed1997

Energy values of non-starch polysaccharides: comparative studies in humans and rats.

Energy values of non-starch polysaccharides (NSP) were estimated from NSP fermentability and from digestible energy balances in human subjects and in rats. During four studies, humans consumed four low fiber control diets and six high fiber diets. For the rat diets, duplicates of the foods consumed by humans were mixed together, freeze-dried and ground. Calculated from fermentability, partial digestible energy values of NSP in humans and rats, respectively, were 8.2 +/- 1.3 and 5.7 +/- 1.2 (P = 0.0013, fruits and vegetables), 11.4 +/- 0.7 and 5.7 +/- 3.2 (P = 0.0001, citrus fiber), 5.0 +/- 2.1 and 2.2 +/- 3.3 (P = 0.0429, barley fiber at high protein intake), 4.4 +/- 1.8 and 2.4 +/- 2.0 (P = 0.0561, barley fiber at low protein intake), 6.7 +/- 1.4 and 7.6 +/- 1.2 (P = 0.296, coarse whole meal rye bread), and 7.1 +/- 0.6 and 6.1 +/- 1.7 (P = 0.157, fine whole meal rye bread) kJ/g NSP. Calculated from energy balances, partial digestible energy values of NSP in humans and rats, respectively, were 2.1 +/- 3.5 and -5.0 +/- 4.0 (P = 0.026, fruits and vegetables), 10.7 +/- 5.1 and 1.4 +/- 5.6 (P = 0.003, citrus fiber), 1.6 +/- 5.1 and -17.8 +/- 8.6 (P = 0.0001, barley fiber at high protein intake), -2.6 +/- 4.9 and -9.3 +/- 8.2 (P = 0.044, barley fiber at low protein intake), -3.0 +/- 7.0 and 0.9 +/- 2.5 (P = 0.27, coarse whole meal rye bread), and 0.9 +/- 5.1 and 0.6 +/- 3.7 (P = 0.89, fine whole meal rye bread) kJ/g NSP. Net energy values were 70% of digestible energy values. Differences between species were significant for NSP in fruits and vegetables, citrus fiber, and barley fiber at high protein intake. Most energy values calculated from energy balances were significantly lower than values calculated from NSP fermentation, with differences being greater in rats than in humans. Thus, the energy values of some types of NSP contained in mixed diets could not be estimated accurately from NSP fermentability either in humans or rats. In addition, our results suggest that the rat is not always a suitable model of humans for predicting energy values of NSP in mixed diets.

Adult↗

PubMed1997

Fermentation in human subjects of nonstarch polysaccharides in mixed diets, but not in a barley fiber concentrate, could be predicted by in vitro fermentation using human fecal inocula.

The fermentation of nonstarch polysaccharides (NSP) contained in a low fiber diet, two high fiber diets high or low in protein, and a barley fiber concentrate was determined in balance experiments in six women and in an in vitro batch system using fecal inocula obtained from these same women. In vitro fermentations were performed with fiber residues prepared from duplicates of the fiber-containing foods consumed during the balance trials. Fermentation of total NSP in humans was 83.8 +/- 0.9% (low fiber diet), 61.8 +/- 3.6% (high fiber diet high in protein), 59.2 +/- 3. 9% (high fiber diet low in protein) and 31.2 +/- 7.4% (barley fiber concentrate). Fermentation in vitro differed from fermentation in humans by -4.0 +/- 1.6% (low fiber diet, P < 0.05,), 4.9 +/- 3.7% (high fiber diet high in protein), 8.8 +/- 3.0% (high fiber diet low in protein, P < 0.01) and 19.7 +/- 8.0% (barley fiber concentrate, P < 0.05). Differences between in vivo and in vitro fermentation were most pronounced for NSP-glucose, i.e., cellulose. Production of short-chain fatty acids in vitro corresponded to the fermentability of NSP. The yield of short-chain fatty acids per gram of fermented NSP was similar for the diets (8.8-9.4 mmol) but lower for the barley fiber concentrate (7.4 mmol, P < 0.05). Although differences between the fermentation measured in humans and in vitro were significant for two diets, the magnitude of the differences was such that fermentation of NSP in mixed diets could be predicted with sufficient accuracy in vitro, whereas agreement between the fermentation in vivo and in vitro of NSP in the barley fiber concentrate was not satisfactory.

Adult↗