Biomedical subjects

M Eichner

Publications and source records attributed to M Eichner.

At least 19 recordsLinked to original sources

PubMed2006

Infectiousness of smallpox relative to disease age: estimates based on transmission network and incubation period.

This study investigated the infectiousness of smallpox relative to the onset of fever using a likelihood-based estimation procedure based on the observed transmission network (n=223) and on the distribution of the incubation period (n=379). Who-infected-whom information enabled us to back-calculate the infectiousness by disease age, employing a step function model for infectiousness. Frequency of secondary transmissions was highest between 3 and 6 days after onset of fever, yielding an expected daily frequency of 20.6% (95% CI 15.1-26.4) of the total number of secondary transmissions, which is consistent with previous observations. The estimated cumulative frequency suggests that 91.1% of secondary transmissions occurred up to 9 days after onset of fever. The proposed method appeared to be useful for diseases with an acute course of illness, where transmission was not hampered by depletion of susceptible contacts.

Acute Disease↗

PubMed2006

High infection rates at low transmission potentials in West African onchocerciasis.

Onchocerciasis has been successfully controlled for many years in endemic countries but more than 120 million people are still at risk. Factors which stabilise the persistence of the parasite in the population must be studied to minimise the future risk of re-infection. Among these factors, the relationship between the annual transmission potential and the parasite establishment rate is a main determinant which has to date not been quantified. Using entomological information and palpation data collected by the Onchocerciasis Control Programme in West Africa prior to the initiation of control activities, we derive annual transmission potential-dependent estimates of the parasite establishment rate from statistical analyses and computer simulations. Even at very low transmission intensities, the filarial parasite Onchocerca volvulus can efficiently establish in the human population, originating from an infection process which is strongly limited with respect to the annual transmission potential. Implementing the estimates into a simplified transmission model predicts that the critical annual biting rate, below which transmission is not possible, is much lower than previously assumed. We conclude that under the current strategy of mass distribution of microfilaricides without additional measures of vector control, the risk of re-infection is higher than previously assumed.

Africa, Western↗

PubMed2006

Reinnervation-induced alterations in rat skeletal muscle.

Denervation-induced myofiber atrophy can be reversed by reinnervation. Growing reinnervated myofibers upregulate numerous molecules, many of which determine the muscle fiber type. In the present study we aimed at identifying factors that might contribute specifically to myofiber growth after reinnervation. The common peroneal nerve of 15 male Wistar rats was cut and resutured without delay (9 animals) or with a delay of 4 weeks (6 animals). We studied the transcriptional repertoire of intact reinnervated tibialis anterior muscle by microarray gene analysis. We assessed SC activation by immunolabeling using anti-MyoD and -myogenin antibodies. The percentage of SC expressing MyoD reached up to 50% of M-cadherin+ cells whereas the percentage of SC expressing myogenin was normal (<10%) in all muscles examined. The values of ipsi- and contralateral muscles did not differ significantly from one another between right and left leg (p<0.05). Thirteen known genes were differentially regulated after reinnervation compared with contralateral muscles. Five of them determine the slow-twitch fiber type (four and a half LIM domains 3, cardiac beta-myosin heavy chain, calsequestrin 2, troponin C (slow), and heart myosin light chain), and three of them are neurally regulated (thrombospondin 4, transferrin receptor, cardiac ankyrin repeat protein). The results strengthen the notion that reinnervaton affects the molecular repertoire of the myofibers directly, leading to fiber type transformation and partial reversal of the denervation phenotype. By contrast, SC do not appear to be affected by reinnervation directly. They can be activated both in reinnervated and contralateral muscles, and they do not fully differentiate. This makes them unlikely to contribute to myofiber growth.

Animals↗

PubMed2006

Estimation of the duration of vaccine-induced residual protection against severe and fatal smallpox based on secondary vaccination failure.

BACKGROUND: Understanding the loss of vaccine-induced immunity against smallpox is essential in determining the fraction of those who are still protected in the present population and in constructing effective countermeasures against bioterrorist attacks. METHOD: Three small Australian outbreaks from the 1880s to early 1900s were investigated. Each documented individual age at infection. The case records for Launceston, 1903, further documented the age at vaccination and disease severity, enabling estimates of the duration of protection against severe and fatal smallpox. RESULTS: A significant association between vaccination and death was observed in the outbreak in Sydney, 1881 (odds ratio of death among vaccinated individuals = 0.3; 95% confidence interval (CI): 0.1, 0.8; p = 0.02), where the time since last vaccination was similar for all vaccinated cases. In Launceston, 1903, where the age at vaccination varied widely, the median duration of partial protection against severe and fatal smallpox was estimated to be 31.7 (95% CI: 13.2, 116.2) and 53.9 (95% CI: 25.6, 123.5) years after vaccination, respectively. Whereas those in their 20s are expected to have the highest frequency of vulnerability to smallpox death in the present population, infections among those in their 30s or 40s are expected to be much less fatal. CONCLUSION: Long lasting partial protection was suggested from the outbreak records, the estimated durations of which were roughly consistent with those reported previously. In the event of a bioterrorist attack, those involved in emergency tasks before emergency vaccination practices are re-established should ideally be previously vaccinated individuals in their 30s or 40s.

Australia↗

PubMed2006

Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection.

OBJECTIVES: To investigate postnatal lipopolysaccharide-binding protein (LBP) kinetics in term neonates and to test its diagnostic accuracy for early-onset bacterial infection (EOBI). STUDY DESIGN: A total of 99 neonates with clinical and serological signs of EOBI comprised the study group; 198 neonates with risk factors, but without EOBI, served as controls. LBP, C-reactive protein (CRP) and interleukin-8 (IL-8) were determined. RESULTS: LBP in the noninfected group increased until 24 h after birth (P < 0.05 vs 6 h). LBP and CRP correlated strongly in neonates with suspected EOBI (r = 0.63). Although LBP reached a higher sensitivity than CRP 6 and 12 h after clinical suspicion (45 (24-68) and 79% (54-94) vs 9 (0-24) and 39% (17-64); P < 0.05)), EOBI was most reliably detected by IL-8. CONCLUSION: LBP kinetics were age-dependent. LBP was not sufficiently sensitive in the prediction of EOBI.

Acute-Phase Proteins↗

PubMed2004

The relationships between the burden of adult parasites, host age and the microfilarial density in human onchocerciasis.

We investigate the relationship between the microfilarial density in the skin and the burden of adult female Onchocerca volvulus by analysing pre-control nodulectomy data which allow for a direct approach, independent of exposure. The data of 169 patients in Burkina Faso and 182 patients in Liberia represent savannah and forest onchocerciasis in West Africa, respectively. Whereas in Burkina Faso, a saturating relationship between microfilarial density and worm burden suggests the operation of density-dependent processes within human hosts, the Liberian data show a linear relationship implying no density dependence. The differences may derive from differences between both parasite strains, i.e. the savannah or the forest strain of O. volvulus. Consistently for both parasite strains and independent of the worm burden, the microfilarial density increases with host age emphasising the concept of the acquisition of immunological tolerance. In male hosts in Liberia, the microfilarial density increases stronger with the worm burden than in female hosts, whereas such sex-specific differences cannot be found in Burkina Faso. In the methodological part of this investigation, we suggest the beta-distribution to be most appropriate for describing variability in microfilarial densities and we present an approach to consider the uncertainty in the adult parasite burden which cannot be determined precisely in helminth infections. Implications of density dependence are discussed with respect to immunological processes in the human host and with respect to the success of control programs. The relationships described show that regulatory processes between the parasite and the human host are multi-dimensional, operating within a high degree of biological variability.

Age Factors↗

PubMed2004

Modelling transmission, immunity and disease of Haemophilus influenzae type b in a structured population.

An individual-based stochastic simulation model was constructed to study the epidemiology of Haemophilus influenzae type b (Hib) transmission, immunity and invasive disease. Embedded in a demographic model, the transmission model of Hib carriage employs the most important social mixing patterns with three types of contact sites (family, day-care group, and school class). The model includes immunity against invasive Hib disease, initiated and boosted by Hib carriage and cross-reactive bacterial encounters. The model reproduces the observed age patterns in Hib carriage and disease in Finland before large-scale use of the Hib conjugate vaccines. The model was used to investigate characteristics of Hib transmission. The analysis emphasizes transmission between children and adults in families while pointing out the importance of pre-school and school-aged children in maintaining Hib circulation. Carriage in these age groups is thus identified as being essential to target for sustained effects of interventions by vaccination.

Adolescent↗

PubMed2004

The influence of competition and vaccination on the coexistence of two pneumococcal serotypes.

Streptococcus pneumoniae (pneumococcus) is one of the most important bacterial pathogens and a leading cause of mucosal infections (e.g. otitis media) and various forms of serious diseases (e.g. pneumonia, meningitis, bacteraemia) in developing and developed countries. Based on the polysaccharide capsule, there are at least 90 different pneumococcal serotypes, which may compete with each other to colonize the nasopharynx. Newly developed protein-polysaccharide conjugated vaccines have been shown to provide protection against disease caused by the serotypes included in the vaccine, and also against colonization (carriage). It is feared that yet uncommon, but nonetheless pathogenic serotypes which have been suppressed by competition, may become more prevalent in carriage and disease after large-scale use of conjugate vaccines. In this paper, we use transmission models of pneumococcal carriage to study how competition and vaccination influence the coexistence of two serotypes. According to our results, direct (physical) competition between two pneumococcal serotypes only influences colonization if the duration of naturally acquired immunity is short. By contrast, indirect (antibody-mediated) competition is of influence only if naturally acquired immunity is long lasting. Vaccination reduces the prevalence of the target serotype--an effect that is enforced by the presence of directly competing bacteria. The emergence of a non-target serotype after vaccination is only observed if bacteria compete directly. These results emphasize the importance of studying whether bacteria compete directly or indirectly and for how long people are protected in order to assess the long-term effects of sero-competition.

Carrier State↗

PubMed2003

On the interpretation of age-intensity profiles and dispersion patterns in parasitological surveys.

The present paper describes how age-intensity profiles of macroparasite burdens are affected by processes underlying the distribution of the parasite numbers in host populations. In a comparative way, we consider the following 6 processes: (i) age-dependent exposure, (ii) parasite-induced host mortality, (iii) heterogeneity within, the host population, (iv) clumped infection, (v) density-dependent parasite mortality and (vi) density-dependent parasite establishment. For each of these processes, we show typical patterns in the age-intensity profile and provide, if possible, explicit and simple solutions for the age-dependent mean parasite burden and the corresponding dispersion patterns. Emphasis is given to density-dependent parasite establishment and to age-intensity profiles resulting from the superposition of different processes. By means of 2 examples we show that the interpretation of observed patterns can be ambiguous if more than 1 process takes place. These findings underline that age-intensity profiles should be interpreted on the basis of available a priori knowledge about the processes assumed to be involved. For purposes of testing different hypotheses, a simulation program is provided with which discrepancies between model prediction and data can be explored.

Aging↗

PubMed2003

The influence of Emla cream on cutaneous microcirculation.

Emla cream is frequently used in surgical dermatology and in anesthesiology, for instance, during vascular surgery procedures. Because local anesthetics can have a vasoactive effect in addition to producing analgesia, we decided to document the effect of 5% Emla cream on cutaneous circulation in a prospective, placebo-controlled study. Skin circulation was monitored continuously under standardized conditions using video capillaroscopy, laser Doppler flowmetry and skin temperature. Recordings were made at the nailfold of the fourth finger (DIV) of the left hand of 12 volunteers with healthy veins over an observation period of 60 minutes under either Emla occlusive dressing or an occlusive dressing with placebo. Mean capillary red blood cell velocity changed only minimally under the Emla occlusive dressing, while placebo occlusive dressing led to a reduction of mean capillary red blood cell velocity from 0.21 mm/s to 0.12 mm/s (p<0.01). There was no statistically significant change of arterial capillary diameter under Emla or placebo occlusive dressing. Skin temperature dropped after 60 minutes of Emla cream occlusive dressing from an initial 26.7 to 24.0 degrees C (-10.1%; p<0.02). The same duration of placebo caused skin temperature to drop from 27.6 to 23.0 degrees C (-16.7%; p<0.001). Laser Doppler flux (543 nm) rose 13% with Emla (p=0.9) and dropped 41.9% under placebo occlusive dressing (p<0.03). Emla cream upregulated nutritive perfusion. No clinically relevant vasoconstrictive effects are expected from an application period of 60 minutes.

Adult↗

PubMed2002

Estimation of the time-dependent vaccine efficacy from a measles epidemic.

We present a method to estimate the time-dependent vaccine efficacy from the cohort-specific vaccination coverage and from data on the vaccination status of cases and apply it to a measles epidemic in Germany which involved 529 cases, 88 of whom were vaccinated and 370 unvaccinated (for the remaining 71 cases the vaccination status is unknown). Our epidemiological model takes into account that maternal antibodies prevent successful vaccination and that vaccine immunity may be lost over time. Model parameters are estimated from the data using maximum likelihood. Vaccination coverage, as determined in school surveys, ranged from 27.6 per cent for the cohort born in 1974 to 85 per cent for the 1986 cohort, which is far too low to prevent measles transmission. Cohorts for which no school surveys were performed are omitted from analysis. Thus, sufficient data are available for only 282 cases, 69 of whom are vaccinated. According to our estimates, measles vaccinations provided no immunity before 1978 (95 per cent CI: 0 to 47 percent), for the period 1978-1982, the estimated vaccine efficacy was 80 percent (95 percent CI: 67 to 89 percent), and for 1982-1990 it was 97 percent (95 percent CI: 93 to 99 percent). After 1990, the estimated value dropped to 89 per cent, but its confidence interval widely overlaps with that of the previous period (95 percent CI: 74 to 97 percent). Loss of immunity was estimated to be zero (95 percent CI: 0 to 0.003/year). Several sensitivity analyses were performed with respect to the model assumptions. A modified model which assumed constant efficacy at all vaccination times yielded a high estimate of 96 per cent (95 percent CI: 92 to 98 percent) for primary vaccine efficacy but also a high loss rate of immunity of 0.007/year (95 percent CI: 0.001 to 0.012) to explain the high fraction of vaccinated cases among older individuals. The likelihood score value is however significantly inferior compared to the score value of the model with time-dependent vaccine efficacy.

Child↗

PubMed2001

Plasmodium falciparum parasitaemia described by a new mathematical model.

A new mathematical model of Plasmodium falciparum asexual parasitaemia is formulated and fitted to 35 malaria therapy cases making a spontaneous recovery after primary inoculation. Observed and simulated case-histories are compared with respect to 9 descriptive statistics. The simulated courses of parasitaemia are more realistic than any previously published. The model uses a discrete time-step of 2 days. Its realistic behaviour was achieved by the following combination of features (i) intra-clonal antigenic variation, (ii) large variations of the variants' baseline growth rate, depending on both variant and case, (iii) innate autoregulation of the asexual parasite density, variable among cases, (iv) acquired variant-specific immunity and (v) acquired variant-transcending immunity, variable among cases. Aspects of the model's internal behaviour, concerning variant dynamics, as well as the respective contributions of the three control mechanisms (iii) - (v), are displayed. Some implications for pathogenesis and control are discussed.

Animals↗

PubMed2001

[Medical compression therapy].

In order to evaluate the correlation between the pressure exerted by compression stockings and a resulting improvement in venous hemodynamics, we carried out an open, randomized, prospective study on 22 patients (11 women and 11 men with an average age of 55.1 [10.3]) with chronic venous insufficiency (CVI) in the clinical stages C1-4, Ep, AS, Ap, PR. Dynamic strain gauge plethysmography was used to measure the acute effect on venous hemodynamics of 9 different compression stockings in compression class 2 (A-D). At the same time when venous function parameters were monitored, we also measured the pressure exerted by the compression stockings during rest and exercise. With all compression stockings the average resting pressure fulfilled in reclined patients the specifications for compression class 2 (25-35 mmHg at the ankle, CEN). The compression stockings lengthened venous refill time t0 in a statistically significant degree. The improvement in venous function was correlated with the ratios of maximal working pressure to resting pressure while standing (r = 0.97, p < 0.001). Compression stockings belonging to the same compression class vary in their acute effect on venous hemodynamics. The efficiency of the different therapeutic compression stockings was largely dependent on the amount of fabric stretch, which can be characterized in vivo with the ratio of maximum exerted pressure during movement to that while standing still. A knowledge of the hemodynamic effectivity of the various compression stockings allows the optimal stocking selection for each patient and his individual clinical situation.

Adult↗

PubMed2000

Modelling the transition of asexual blood stages of Plasmodium falciparum to gametocytes.

In this paper, we investigate the transition of asexual blood stages of P. falciparum to gametocytes. The study is based on daily data, collected from 262 individual courses of parasitaemia. We propose several mathematical models that follow biological reasoning. The models are fitted with maximum likelihood and are compared with each other. The models differ in the assumptions made about the mortality of circulating gametocytes and about the transition rate of the asexual parasites. Gametocyte mortality is modelled as being (i) constant over time, (ii) linearly increasing over time, (iii) linearly increasing over gametocyte age, and (iv) exponentially increasing over gametocyte age, respectively. The transition rate is either kept constant per patient or piecewise constant within intervals that correspond to waves of asexual parasitaemia which are assumed to be caused by different Pf(emp1)-variants. According to likelihood ratio tests, the models with age-dependent mortality rate and wave-dependent transition rates are superior to the models with constant transition rate and/or constant or time-dependent mortality rate. The best fits are reached for models with exponentially increasing (Gompertz-type) mortality. Furthermore, an impact of high asexual parasite densities on the survival of gametocytes, interpreted as a cytokine-mediated effect, is evident in some cases.

Animals↗

PubMed2000

[A new optoelectronic measuring device for assessment of leg circumference in comparison with manual measurement].

For compression treatment to be effective in patients with chronic venous insufficiency, it is vital that leg circumference be measured accurately. If compression stockings are custom fit and appropriate for the medical indications, patient compliance will be high. Exact measurements of circumference and length are prerequisites for a good fit. The aim of the present study was to compare an opto-electronic device for the contact-free measurement of calf circumference with the conventional manual method using a tape measure. We investigated the differences between the results obtained with the two methods, and also their reproducibility. Circumferences were measured at defined heights on an anatomically shaped non-yielding leg model and on the leg of a healthy volunteer by 10 different experimenters both with the tape measure and with the opto-electronic device. The calf circumferences measured manually with the tape measure varied significantly more than those measured opto-electronically, both in the leg model and in the leg of the volunteer. A systematic error in the opto-electronic method appears unlikely, since the manual measurements on the leg model were both larger and smaller than those obtained with the opto-electronic device. Reproducibility was exceptionally high with the opto-electronic device (standard deviation 0.11-0.42 cm). The opto-electronic method yields rapid accurate measurements of circumference with excellent intra- and inter-operator reproducibility.

Anthropometry↗

PubMed1999

C-fos protein expression in the nucleus of the solitary tract correlates with cholecystokinin dose injected and food intake in rats.

C-fos protein expression was investigated in the nucleus of the solitary tract (NTS) in response to increasing cholecystokinin (CCK) doses and food intake in rats by counting the number of c-fos protein positive cells in the NTS. C-fos protein expression in the NTS dose-dependently increased in response to CCK, the lowest effective dose being 0.1 microg/kg. The ED(50) for c-fos protein expression in the NTS in response to CCK was calculated to be 0.5 to 1.8 microg/kg, depending on the anatomical level of the NTS investigated. Food intake increased c-fos protein expression in the NTS, the maximum number of c-fos protein positive cells being reached at 90 min after the start of food intake. Regression analysis identified a positive correlation between c-fos protein expression and the amount of food intake. Our data indicate that subpopulations of the NTS that are activated by CCK or food intake are involved into the short-term regulation of food intake and the neural control of feeding by the caudal brainstem.

Animals↗

PubMed1999

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules.

OBJECTIVE: Increased levels of soluble adhesion molecules, a decreased PO2/FIO2 ratio and a tendency to worsened outcome have been reported following the use of human albumin in critical illness. The reasons are not yet understood. Since albumin solutions have previously been shown to contain proinflammatory mediators, a direct upregulation of adhesion molecules by contaminated batches may explain these findings. To examine this, we studied the effects of different albumin preparations on endothelial cell adhesion molecules in vitro. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human umbilical venous endothelial cell cultures (n = 4) were incubated for 6 h at 5 mg/ml with four different human albumin solutions (HA1-4) from different manufacturers. Medium served as the control. Using flow cytometry, the effects on E-selectin, ICAM-1 and VCAM-1 expression were determined on unstimulated cells and on cells stimulated with tumour necrosis factor alpha at 0.5 ng/ml for 4 h. MEASUREMENTS AND RESULTS: On unstimulated cells, HA1 and HA4, two different batches from the same manufacturer, increased ICAM-1 by 22% and 15%, respectively. After stimulation, both solutions resulted in a 19% increased expression of E-Selectin. In addition, HA4 decreased VCAM-1 on stimulated cells (p < or = 0.05). Two albumin preparations from other manufacturers did not produce significant effects. CONCLUSIONS: Some albumin solutions directly modulate adhesion molecule expression on endothelial cells. This may, at least in part, explain the previous finding of increased soluble adhesion molecules and a decreased PO2/FIO2 ratio in critically ill patients undergoing volume replacement with human albumin.

Albumins↗

PubMed1999

A hierarchical Bayesian model to predict the duration of immunity to Haemophilus influenzae type b.

A hierarchical Bayesian regression model is fitted to longitudinal data on Haemophilus influenzae type b (Hib) serum antibodies. To estimate the decline rate of the antibody concentration, the model accommodates the possibility of unobserved subclinical infections with Hib bacteria that cause increasing concentrations during the study period. The computations rely on Markov chain Monte Carlo simulation of the joint posterior distribution of the model parameters. The model is used to predict the duration of immunity to subclinical Hib infection and to a serious invasive Hib disease.

Antibodies, Bacterial↗