bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis
Authors: Esfandiarpour Iraj , Alavi Afsáneh
Published: March 2003

Background Cutaneous leishmaniasis is a common disease in Iran, particularly in Kerman province. It usually occurs via the bite of an infected sandfly.

Methods One hundred and fifty patients suffering from cutaneous leishmaniasis were included in this study in Kerman. The patients were randomly divided into three groups. They were matched with regard to age, sex, duration of the disease, and type, number, and site of the lesions. For each group, one of the following therapeutic methods was applied: (i) oral allopurinol (15 mg/kg/day) for 3 weeks; (ii) intramuscular injection of Glucantime (30 mg/kg/day), corresponding to 8 mg/kg/day of pentavalent antimony, for 2 weeks; (iii) combined therapy. The lesions were re‐examined at the end of treatment and 2 and 4 weeks later. The response to treatment was graded as excellent (reduction in the size of the lesion by at least 80% or complete clearance), good (reduction in the size of the lesion by 50%), and poor (minimal or no change in the lesion).

Results The overall results indicated that 18% of patients showed excellent response, 6% good response, and 76% poor response in the first group. In the second group, 24% of patients showed excellent response, 6% good response, and 70% poor response. In the third group, 46% of patients showed excellent response, 8% good response, and 46% poor response.

Conclusions The results obtained by the three therapeutic methods indicated that combined therapy with allopurinol plus Glucantime was much more effective than that obtained by each of the two drugs when used alone (P < 0.05).
Leukoderma punctatum following systemic PUVA therapy
Authors: Dogra Sunil , Jain Rajesh , Parsad Devinder , Handa Sanjeev
Published: March 2003

A 35‐year‐old woman with vitiligo vulgaris had been treated with psoralen plus UVA (PUVA) therapy for 15 months. She was given 4,5′,8‐trimethylpsoralen (0.6 mg/kg 3 days/week) and UVA exposure (UV 7001 K Waldmann PUVA chamber). She developed repigmentation over more than 50% of the vitiliginous area over a period of 1 year. During the last 6 months, she developed three to four episodes of acute phototoxic reactions, and UVA exposure had to be interrupted. This phototoxic response was probably partly due to excessive UV radiation exposure of the lesions on exposed sites as a result of the natural bright sunshine in India. On regular monthly assessment, numerous tiny hypopigmented macules, round to oval in shape with sharp margins and measuring about 1.5 mm, were distributed over the repigmented areas (Fig. 1). The lesions were predominantly seen over the extremities and were distributed randomly without any perifollicular or marginal predilection. Considering the typical morphology and distribution of the lesions, a clinical diagnosis of leukoderma punctatum was made and a skin biopsy was taken from one such lesion. On histopathology examination, patchy loss of melanin in the basal layer was observed without any other remarkable change in the epidermis.

Multiple, discrete, hypopigmented, punctiform macules measuring about 1–1.5 mm over the thigh

image
Wells’ syndrome: a clinical and histopathologic review of seven cases
Authors: Moossavi Meena , Mehregan Darius R.
Published: March 2003

Wells’ syndrome, or eosinophilic cellulitis, is characterized clinically by an acute dermatitis resembling cellulitis, which evolves into violaceous plaques that resolve spontaneously without scarring. The histopathologic features are dynamic, starting with dermal edema and infiltration of eosinophils, the development of “flame figures,” and finishing with the appearance of phagocytic histiocytes. We present the clinical and histopathologic features of seven cases of eosinophilic cellulitis.
Genotype–environment interaction and the ontogeny of diet-induced phenotypic plasticity in size and shape of Melanoplus femurrubrum (Orthoptera: Acrididae)
Authors: Thompson
Published: March 2003

The developmental origin of phenotypic plasticity in morphological shape can be attributed to environment-specific changes in growth of overall body size, localized growth of a morphological structure or a combination of both. I monitored morphological development in the first four nymphal instars of grasshoppers (Melanoplus femurrubrum) raised on two different plant diets to determine the ontogenetic origins of diet-induced phenotypic plasticity and to quantify genetic variation for phenotypic plasticity. I measured diet-induced phenotypic plasticity in body size (tibia length), head size (articular width and mandible depth) and head shape (residual articular width and residual mandible depth) for grasshoppers from 37 full-sib families raised on either a hard plant diet (Lolium perenne) or a soft plant diet (Trifolium repens).

By the second to third nymphal instar, grasshoppers raised on a hard plant diet had significantly smaller mean tibia length and greater mean residual articular width (distance between mandibles adjusted for body size) compared with full-sibs raised on a soft plant diet. However, there was no significant phenotypic plasticity in mean unadjusted articular width and mandible depth, and in mean residual mandible depth. At the population level, development of diet-induced phenotypic plasticity in grasshopper head shape is mediated by plastic changes in allocation to tissue growth that maintain growth of head size on hard, low-nutrient diets while reducing growth of body size. Within the population, there was substantial variation in the plasticity of growth trajectories since different full-sib families developed phenotypic plasticity of residual articular width through different combinations of head and body size growth.

Genetic variation for diet-induced phenotypic plasticity of residual articular width, residual mandible depth and tibia length, as estimated by genotype–environment interaction, exhibited significant fluctuation through ontogeny (repeated measures MANOVA, family × plant × instar, P < 0.01). For example, there was significant genetic variation for phenotypic plasticity of residual articular width in the third nymphal instar, but not earlier or later in ontogeny. The observed patterns of genetic variation are discussed with reference to short-term constraints and the evolution of phenotypic plasticity.
Does natural selection alter genetic architecture? An evaluation of quantitative genetic variation among populations of Allonemobius
socius and A. fasciatus
Authors: Roff  , Mousseau
Published: March 2003

To make long-term predictions using present quantitative genetic theory it is necessary to assume that the genetic variance–covariance matrix (G) remains constant or at least changes by a constant fraction. In this paper we examine the stability of the genetic architecture of two traits known to be subject to natural selection; femur length and ovipositor length in two species of the cricket Allonemobius. Previous studies have shown that in A. fasciatus and A. socius natural selection favours an increased body size southwards but a decreased ovipositor length. Such countergradient selection should tend to favour a change in G. In the total sample of eight populations of A. socius and one of A. fasciatus we show that there is significant variation in all genetic covariance components, i.e. VA for body size, VA for ovipositor length, and CovA. This variation results entirely from an increase in the covariances of A. fasciatus. However, although larger, these components are approximately proportionally increased, thereby leading to no statistically significant change in the genetic correlation. A proportional increase in the covariance components is consistent with changes resulting from genetic drift. On the other hand, the genetic covariance components are significantly correlated with the length of the growing season suggesting that the change in the genetic architecture is the result of selection and drift.
Reaction norms across and genetic parameters at different temperatures for thorax and wing size traits in Drosophila aldrichi and D. buzzatii
Authors: Loeschcke  , Bundgaard  , Barker
Published: March 2003

Reaction norms across seven constant and one fluctuating temperature of development were measured for thorax length and several wing size traits for up to 10 isofemale lines of each of the cactophilic Drosophila species, D. aldrichi and D. buzzatii, originating from the same locality. Maximum thorax length was reached at different low to intermediate temperatures for the two species, whereas wing length was highest at the lowest temperature in both species. Various ratio parameters showed pronounced species differences. The reaction norm for the wing loading index (wing length/thorax length) decreased monotonically with temperature in both species, but was much steeper and spanned a wider range in D. aldrichi than in D. buzzatii, suggesting either that wing loading is not a good characterization of flight capacity or, more likely, that flight optimization does not occur in the same manner in both species. The vein ratio (distal length/proximal length of the third vein) increased with temperature in D. buzzatii but decreased in D. aldrichi. Wing development in the two species thus is very different, with the proximal part of the wing in D. buzzatii more closely allied to the thorax than to the distal part. Among line variation was significant for all traits in both species, and most pronounced for thorax length and the ratio parameters. Coefficients of variation were significantly different between the species for all traits, with those in D. aldrichi higher than in D. buzzatii. Genetic variance in plasticity was significant for all traits in D. buzzatii, but only for seven out of 12 in D. aldrichi. Additive genetic variances for all traits in both species were significantly larger than zero. Genetic correlations between thorax length and several wing length parameters, and between these and wing area, were positive and generally significant in both species. The genetic correlation between the distal and the proximal length of the third vein was not significantly different from zero in D. aldrichi, but negative and significant in D. buzzatii. Heritabilites varied significantly among temperatures for almost all traits in both species. Phenotypic variances were generally higher in D. aldrichi than in D. buzzatii, and commonly highest at the extreme temperatures in the former species. At the high temperature the genetic variances also were usually highest in D. aldrichi. The data clearly suggest that the process of thermal adaptation is species specific and caution against generalizations based on the study of single species.
Vertebral numbers in male and female snakes: the roles of natural, sexual and fecundity selection
Authors: Shine
Published: March 2003

The relative numbers of trunk (body) and caudal (tail) vertebrae in snakes might be influenced by at least four processes: (1) natural selection for crawling speed, (2) fecundity selection for larger trunk size in females, (3) sexual selection for longer bodies or tails in males and/or (4) developmental constraints (if an increase in the number of body vertebrae requires a decrease in the number of tail vertebrae, or vice versa). These four hypotheses generate different predictions about the relationship between sex differences in the numbers of body vertebrae vs. tail vertebrae. I collated published data to test these predictions, both with raw data and using phylogenetically independent contrasts. Some snake lineages show a negative correlation between the magnitude of sex disparities in trunk vs. caudal vertebrae whereas other lineages show the reverse pattern, or no correlation. Thus, different selective pressures seem to have been important in different lineages. Vertebral numbers in snakes may offer a useful model system in which to explore the conflicts between natural, fecundity and sexual selection.
Effective population size, reproductive success and sperm precedence in the butterfly, Bicyclus anynana, in captivity
Authors: Brakefield P. M. , El Filali E. , Van Der Laan R. , Breuker C. J. , Saccheri I. J. , Zwaan B.
Published: March 2003

A pedigree approach is used to estimate the effective population size yn two population cages of the butterfly, Bicyclus anynana. Each cage was founded with 54 individually marked adults of each sex. Matings were recorded over a 3-day period. Eggs were then collected from each female over a similar period before the numbers of hatching larvae were counted to assess progeny number. The males showed a higher variance in reproductive success than the females. Since about one-quarter of all females mated more than once, we also examined the pattern of sperm precedence using molecular markers or, in separate crossing experiments, wing pattern mutants. Both instances of complete first and last male sperm precedence, as well as of sperm mixing, were found. In some crosses a ‘leakiness’ was found in which some of the early eggs laid by a female were fertilized by a male partner which was subsequently completely unsuccessful. However, the estimates of effective population size were largely unaffected by the pattern of sperm precedence. Estimates for Ne : N in each cage were close to 0.60. The possibility of obtaining comparable estimates in selected natural populations of butterflies is discussed.
Immune stress and facultative sex in a parasitic nematode
Authors: West S. A. , Gemmill A. W. , Graham A. , Viney M. E. , Read A. F.
Published: March 2003

It has been suggested that sexual reproduction in parasites may be advantageous because it helps evade genotype-specific host immune responses. Indirect support for this hypothesis has recently come from work on Strongyloides ratti, a parasitic nematode of rats that develops and reproduces sexually or asexually. In this species, host immune responses against S. ratti lead to a higher proportion of individuals reproducing sexually. However, an alternative explanation for these results is that sex is favoured by general environmental stress, including host responses against antigen sources other than S. ratti. Here we test this hypothesis, by determining how host immunity against two other parasitic nematode species (Nippostrongylus brasiliensis & Strongyloides venezuelensis) and commonly used mammalian antigens (sheep red blood cells) affects the likelihood of S. ratti larvae developing sexually. Our results show that increased levels of sex occur in response to immune responses generated against these other species, and not just host immunity elicited by S. ratti. This is consistent with the idea that sex is favoured under stressful conditions, and does not support the immune evasion hypothesis.
Sexual selection in an isopod with Wolbachia-induced sex reversal: males prefer real females
Authors: Moreau J. , Bertin A. , Caubet Y. , Rigaud T.
Published: March 2003

A variety of genetic elements encode traits beneficial to their own transmission. Despite their ‘selfish’ behaviour, most of these elements are often found at relatively low frequencies in host populations. This is the case of intracytoplasmic Wolbachia bacteria hosted by the isopod Armadillidium vulgare that distort the host sex ratio towards females by feminizing the genetic males they infect. Here we tested the hypothesis that sexual selection against Wolbachia-infected females could maintain a polymorphism of the infection in populations. The infected neo-females (feminized males) have lower mating rates and received less sperm relative to uninfected females. Males exhibited an active choice: they interacted more with uninfected females and made more mating attempts. A female behavioural difference was also observed in response to male mating attempts: infected neo-females more often exhibited behaviours that stop the mating sequence. The difference in mating rate was significant only when males could choose between the two female types. This process could maintain a polymorphism of the infection in populations. Genetic females experimentally infected with Wolbachia are not exposed to the same sexual selection pressure, so the infection alone cannot explain these differences.
Deconstructing a floral phenotype: do pollinators select for corolla integration in Lavandula latifolia?
Authors: Herrera C. M.
Published: March 2003

An experimental field study was undertaken to assess whether correlational selection generated by pollinators can account for observed phenotypic integration of the two corolla lips in the zygomorphic flowers of the insect-pollinated Mediterranean shrub, Lavandula latifolia (Labiatae). The experiment consisted of manipulating the upper and lower corolla lips according to a two-way factorial design with interaction, and involved the complete (lower lip) or extensive (distal two thirds of upper lip) excision of one or the two lips. Per-flower male (proportion of pollen grains removed) and female (number of pollen tubes down the style) pollination success, and maternal fecundity (seed set), of experimental flowers were evaluated after exposure to natural pollination in the field. Artificially induced corolla variation had no significant effects on either male or female pollination success, and two aberrant floral morphologies, characterized by lack of corolla integration, had a maternal fecundity advantage over normal two-lipped phenotypes. These results do not support a predominant role of correlational selection by pollinators in maintaining corolla integration in L. latifolia, but are instead consistent with the alternative view that integration is mainly the consequence of genetic and/or developmental factors.
Sex differences in survival selection in the serin, Serinus serinus
Authors: Björklund M. , Senar J. C.
Published: March 2003

Natural selection is demonstrated in most natural populations which suggests that populations are dispatched from their adaptive peaks as a result of selection on correlated characters, or conflicting selection between the sexes. We analysed patterns of survival selection in a population of serins (Serinus serinus) outside Barcelona over a period of 13 years. There was directional selection for increased wing length in males and females accompanied by strong disruptive selection on both tail and wing length in males and a selection against a positive correlation between the two characters in males. In females there was directional selection for increased bill width but decreased bill depth, which should be contrasted to the stabilizing selection acting on bill depth in males. There were conflicting selection on the characters within a sex and conflicting selection of the same characters between sexes, which constrain the rate of access to the nearest adaptive peak.
Phylogeography of a Palaearctic sedentary passerine, the willow tit (Parus montanus)
Authors: Kvist L. , Martens J. , Ahola A. , Orell M.
Published: March 2003

We analysed variation of the mitochondrial control region from willow tits through its Palaearctic distribution range. Although we found high amount of genetic variation (π=1.114%), there was almost no differentiation between subspecies or geographical localities. This may be because of a combination of several ecological and genetic factors, including a relatively homogenic habitat through the distribution range, lack of geographical barriers, high gene flow and a large long-term effective population size. On the contrary, in the songar tit, which is sometimes considered to be conspecific with the willow tit, the mitochondrial lineages seem to correlate with the geographical locality and are clearly distinct from the willow tit. We concluded that the common ancestors of willow and songar tits existed some 1.5–2 Myr ago in the south-eastern Asia. After the last Ice Ages, the willow tit expanded all through the Palaearctic, whereas the songar tit remained in eastern Asia.
Multiple mating, sperm transfer and oviposition pattern in the giant sperm species, Drosophila bifurca
Authors: Méry F. , Joly D.
Published: March 2003

Many diverse traits are involved in gamete systems, and several models have analysed sperm length variation in terms of the intensity of sperm competition. This study investigates mating, sperm transfer and oviposition patterns in Drosophila bifurca, which possesses the longest sperm in the animal kingdom (about 6 cm). The prediction is that sperm gigantism should prevent male–male interaction. In this study, we examine how sperm transfer varies as males mate with a series of females, and how female receptivity changes with time after mating. As predicted, we found an extremely limited overlap of ejaculates owing to (1) reduced sperm transfer to females that had already mated, and (2) female remating depended both on the amount of sperm transferred and the modes of egg laying. The amount of sperm transferred to the female is discussed in relation to the peculiar morphology of the male reproductive tract and to sexual dimorphism and ecological hypotheses.
Genetic variability and phylogeographical patterns of a nonindigenous species invasion: a comparison of exotic vs. native zebra and quagga mussel populations
Authors: Stepien C. A. , Taylor C. D. , Dabrowska K. A.
Published: March 2003

There have been few investigations of the number of founding sources and amount of genetic variability that lead to a successful nonindigenous species invasion, although genetic diversity is believed to play a central role. In the present study, population genetic structure, diversity and divergence patterns were analysed for the zebra mussel Dreissena polymorpha [n=280 samples and 63 putative randomly amplified polymorphic DNA (RAPDs) gene loci] and the quagga mussel D. bugensis (n=136 and 52 loci) from 10 nonindigenous North American and six Eurasian sampling sites, representing their present-day ranges. Results showed that exotic populations of zebra and quagga mussels had surprisingly high genetic variability, similar to those in the Eurasian populations, suggesting large numbers of founding individuals and consistent with the hypothesis of multiple colonizations. Patterns of genetic relationships indicate that the North American populations of D. polymorpha likely were founded by multiple source populations from north-western and northcentral Europe, but not from southcentral or eastern Europe. Sampling areas within North America also were significantly divergent, having levels of gene flow and migration about twice those separating long-established Eurasian populations. Samples of D. bugensis in Lakes Erie and Ontario were significantly different, with the former being more closely related to a native population from the Dnieper River, Ukraine. No evidence for a founder effect was discerned for either species.
The Ratchet and the Red Queen: the maintenance of sex in parasites
Authors: Howard R. S. , Lively C. M.
Published: March 2003

The adaptive significance of sexual reproduction remains as an unsolved problem in evolutionary biology. One promising hypothesis is that frequency-dependent selection by parasites selects for sexual reproduction in hosts, but it is unclear whether such selection on hosts would feed back to select for sexual reproduction in parasites. Here we used individual-based computer simulations to explore this possibility. Specifically, we tracked the dynamics of asexual parasites following their introduction into sexual parasite populations for different combinations of parasite virulence and transmission. Our results suggest that coevolutionary interactions with hosts would generally lead to a stable coexistence between sexual parasites and a single parasite clone. However, if multiple mutations to asexual reproduction were allowed, we found that the interaction led to the accumulation of clonal diversity in the asexual parasite population, which led to the eventual extinction of the sexual parasites. Thus, coevolution with sexual hosts may not be generally sufficient to select for sex in parasites. We then allowed for the stochastic accumulation of mutations in the finite parasite populations (Muller's Ratchet). We found that, for higher levels of parasite virulence and transmission, the population bottlenecks resulting from host–parasite coevolution led to the rapid accumulation of mutations in the clonal parasites and their elimination from the population. This result may explain the observation that sexual reproduction is more common in parasitic animals than in their free-living relatives.
Within- and among-population variation in infectivity, latency and spore production in a host–pathogen system
Authors: Kaltz O. , Shykoff J. A.
Published: March 2003

In spatially structured populations, host–parasite coevolutionary potential depends on the distribution of genetic variation within and among populations. Inoculation experiments using the plant, Silene latifolia, and its fungal pathogen, Microbotryum violaceum, revealed little overall differentiation in infectivity/resistance, latency or spore production among host or pathogen populations. Within populations, fungal strains had similar means, but varied in performance across plant populations. Variation in resistance among seed families indicates the potential for parasite-mediated selection, whereas there was little evidence for local pathogen genotype × plant genotype interactions assumed by most theoretical coevolution models. Lower spore production on sympatric than allopatric hosts confirmed local fungal maladaptation already observed for infectivity. Correlations between infectivity and latency or spore production suggest a common mechanism for variation in these traits. Our results suggest low variation available to this pathogen for tracking its coevolving host. This may be caused by random drift, breeding system or migration characteristic of metapopulation dynamics.
Early maternal effects and antibacterial immune factors in the eggs, nestlings and adults of the barn swallow
Authors: Saino N. , Dall'ara P. , Martinelli R. , Møller A. P.
Published: March 2003

Transfer of immune factors via the egg may represent a maternal adaptation enhancing offspring survival. Lysozyme is a major component of maternal antibacterial immunity which is transferred to the eggs in birds. In a population of barn swallows (Hirundo rustica), lysozyme activity declined during the prelaying and laying periods in females but not in males. Egg hatching failure decreased with maternal lysozyme activity. The first eggs in a clutch contained more lysozyme and produced nestlings with larger lysozyme activity when 5 days old than last-laid ones. In a cross-fostering experiment where brood size was manipulated, nestling origin but not post-manipulation brood size affected lysozyme activity. Hence, maternal lysozyme varies during the breeding season and may differentially enhance antibacterial immune defence of the eggs and nestlings in relation to laying order. These findings suggest that offspring innate immunity is influenced by early maternal effects.
Latitudinal population differentiation in phenology, life history and flower morphology in the perennial herb Lythrum salicaria
Authors: Olsson K. , Ågren J.
Published: March 2003

In plants with a wide distribution, phenological characters can be expected to vary clinally along climatic gradients, whereas other characters important for adaptation to local biotic and abiotic factors may vary in a more mosaic fashion. We used common-garden experiments and controlled crosses to examine population differentiation in phenology, life history and morphology in the perennial herb Lythrum salicaria along a latitudinal transect through Sweden (57°N to 66°N). Northern populations initiated growth and flowering earlier, flowered for a shorter period, were shorter, produced more and larger winter buds, and were older at first reproduction than southern populations. Flower morphology varied significantly among populations, but was, with the exception of calyx length, not significantly related to latitude of origin. Survival in the common garden (at 63°49′N) was positively correlated with latitude of origin and the size and number of winter buds produced in the preceding year. The results suggest that the among-population differences in phenology and life history have evolved in response to latitudinal variation in length of the growing season. Further studies are required to determine whether population differentiation in flower morphology is maintained by selection.
Screening for viral markers in volunteer and replacement blood donors in West Africa
Authors: Sarkodie F. , Adarkwa M. , Adu‐Sarkodie Y. , Candotti D. , Acheampong J. W. , Allain J. P.
Published: March 2003

Background and Objectives

West Africa is a highly endemic area for viral infections. The prevalence of five viral markers was determined in Ghanaian blood donors.

Materials and Methods

Replacement and volunteer blood donors were screened using enzyme immunoassays (EIAs) for hepatitis B surface antigen (HBsAg), human immunodeficiency virus antibodies (anti‐HIV), HIV p24 antigen, human T‐cell lymphocytotrophic virus‐I and ‐II antibodies (anti‐HTLV‐I/II) and hepatitis C virus antibodies (anti‐HCV).

Results

HBsAg was present at an equally high frequency (15%) in young volunteer (median age 18 years) and older replacement (median age 33 years) blood donors. In contrast, the prevalence of anti‐HIV and anti‐HCV was significantly higher in replacement blood donors (2·4 and 0·3%, respectively, P < 0·001). HCV RNA was detected in 74 or 55% of seropositive donors, depending on the confirmatory criteria used. No p24 antigen‐positive/anti‐HIV‐negative donations were found. The prevalence of HTLV‐I/II was generally low (0·5%).

Conclusion

All blood donations should be screened for hepatitis B virus (HBV), HIV and HCV markers.
Species differences in the blood content of the normal cellular isoform of prion protein, PrPc, measured by time‐resolved fluoroimmunoassay
Authors: MacGregor I. R. , Drummond O.
Published: March 2003

Background and Objectives  The concern that variant Creutzfeldt‐Jakob disease could be transmitted via blood transfusion has prompted studies of blood infectivity in animal models. As normal prion protein acts as a substrate for conversion to the abnormal form associated with infectivity, we have quantified its distribution in mice and hamsters, the most commonly used animal models.

Materials and Methods  A time‐resolved fluoroimmunoassay was used to measure normal prion protein in hamster and mouse tissues, including blood.

Results  Levels of prion protein in hamster blood were remarkably low compared with human blood. In contrast, levels in mouse blood were quite similar to human blood; however, there were differences in the distribution of normal prion between cellular and cell‐free fractions.

Conclusion  Differences between levels of normal prion in blood of animal models and humans should be considered as a possible contributor to infectivity study outcomes in these models.
The development of a national standardized approach for the enumeration of residual leucocytes in blood components
Authors: Cardigan R. , Phipps A. , Seghatchian J. , Bashir S. , Aynsley S. , Beckman N. , Barnett D. , Reilly J. T. , Williamson L. M.
Published: March 2003

Background and ObjectivesThe UK Blood Transfusion Services implemented universal leucocyte depletion of the blood supply in November 1999. To provide statistical process monitoring of these processes, automated methods were introduced to count residual leucocytes (white blood cells) in blood components.

Materials and MethodsInitially in the National Blood Service (NBS) England, protocols were standardized on the use of LeucoCount reagents with either Becton‐Dickinson or Beckman Coulter flow cytometers.

ResultsStandardization of protocols resulted in a decreased intersite variability of red cell samples (from 36% to 9% at a level of 11 and 10 cells/µl, respectively), and 100% of sites (n = 11) fulfilled the validation criteria. However, we also evaluated the use of alternative reagents with the result that reagents from either Becton‐Dickinson or Beckman Coulter, used on either a Becton‐Dickinson or Beckman Coulter flow cytometer, passed our validation criteria.

ConclusionsIt is critical to include samples from filtered products containing white blood cells in validations of leucocyte enumeration methodology, as results may differ between methods using these samples but not using spiked or fixed material. Standardized gating strategies and optimization methods for flow cytometers are critical for obtaining equivalent results with different reagents and instruments.
Making risk statements stick
Authors: Dumont L. J. , AuBuchon J. P.
Published: March 2003

Estimates of risk associated with blood transfusion are reported from a variety of sources using different numerical constructs. These data must be judged for validity and generalizability to facilitate decisions for interventions and to estimate potential benefits of interventions. Risk estimates reported in consistent terms, such as occurrences per million units transfused, will assist in comparisons of risks and the expected effect observed at the practitioner level. Use of the estimated number needed to treat puts the effect of an intervention in perspective for the individual practitioner and for national health authorities. We re‐evaluated data reported from several recent studies of transfusion risk to highlight this approach. In the USA, the number needed to treat estimated to prevent one HIV transmission is 4·3 million (mini‐pool NAT); to prevent one death from bacterial sepsis is 21 thousand (conversion to single donor platelets), and 16 thousand (bacterial screening of platelet concentrates). As interventions are continuing to drive infectious disease transmission rates lower and lower, expressing residual risk as the number needed to treat demonstrates that further improvements in safety are unlikely to be recognized at the local level even though the overall impact at the national level is significant.
Acute staphylococcal peritonitis following cystocentesis in a dog
Authors: Specht Andrew , Chan Daniel , O'Toole Therese , Kent Marc , Benson John , A. Rozanski Elizabeth , E. Rush John
Published: March 2003

Objective:Description of a case of acute gram‐positive peritonitis following cystocentesis and leakage of contaminated urine into the peritoneal cavity.

Case summary:A 6‐year‐old male Standard Poodle was presented for stranguria and was identified to have a urethral obstruction. Attempts at retrograde urethral catheterization failed and a decompressive cystocentesis was performed. Within several hours, the dog became dull, tachycardic, tachypneic, pyrexic and profoundly hypovolemic. Septic peritonitis resulting from the introduction of a staphylococcal organism from a urinary tract infection into the peritoneal cavity was identified. The dog responded well to surgical therapy and medical management.

New or unique information provided:To the authors' knowledge, this is the first detailed report of gram‐positive septic peritonitis resulting from a therapeutic cystocentesis. This is contrary to most other reports of septic peritonitis in dogs, where the causative agent is a gram‐negative organism. The characteristics of sepsis caused by a gram‐positive organism are different and in humans the relative importance of gram‐positive sepsis is increasing.
Beurteilung des Haarverlustes. Klinische Relevanz der Untersuchungsmethoden des Haarwachstums
Authors: Van Neste D.
Published: March 2003

Zusammenfassung: Dieser Übersichtsartikel konzentriert sich auf Wachstumsuntersuchungsmethoden des menschlichen Kopfhaares im Hinblick auf eine klinisch bedeutsame Beurteilung des Haarverlustes. Das Phänomen des Haarausfalls ist das endgültige Resultat von den komplexen Ereignissen des Haarzyklus, in dem es zu einer defekten Haarneubildung gekommen ist. Das methodische Spektrum der Untersuchungen reicht von stark invasiven bis zu weniger invasiven Ansätzen. Die Untersuchungsmethoden sollen hier mit all ihren Stärken und Schwächen betrachtet werden und werden vor allem in Bezug auf ihre potenzielle Anwendung in einer Haut‐ oder Haarklinik diskutiert. Mit den erst kürzlich entwickelten hoch auflösenden, nicht‐invasiven analytischen Methoden kann fast jeder Aspekt des dynamischen Haarwachstums und Haarverlustes betrachtet werden, außerdem ermöglichen diese eine Kalibrierung der bisher mehr allgemeinen Messmethoden. In diesem Artikel wird von dem Autor die Meinung vertreten, dass im Hinblick auf das Monitoring von guten und schlechten Haarwachstumsveränderungen, wie Haarwachstum und ‐verlust, eine Kombination der hoch auflösenden analytischen Messmethoden mit einer allgemeinen Kalibrierungsmethode für eine Klinik am empfehlenswertesten zu sein scheint.
Ernährung und Haarausfall
Authors: Rushton D. H.
Published: March 2003

Zusammenfassung: Die vorliegende Literatur zeigt, wie wenig über Ernährungsfaktoren und Haarausfall bekannt ist. Das vorhandene Wissen resultiert aus Untersuchungen zur Protein‐Mangelernährung, zu Hungerzuständen und Essstörungen.Bei ansonsten gesunden Menschen scheinen bei anhaltendem, vermehrten Haarausfall Ernährungsfaktoren eine Rolle zu spielen. Bereits vor 40 Jahren demonstrierte Hård, wie wichtig eine Eisensubstitution bei nicht‐anämischen Frauen mit Haarausfall und Eisenmangel ist. Die Serum‐Ferritinspiegel erlauben einen guten Einblick in den Eisenstatus eines Patienten. Rushton et al. veröffentlichten erstmals Daten, die verdeutlichten, dass die Bestimmung der Serum‐Ferritinspiegel beim weiblichen Haarausfall wichtig ist und 10 Jahre später bestätigten Kantor et al. diesen Zusammenhang. In welchem Bereich sich der Serum‐Ferritin‐Spiegel bei Personen mit verstärktem Haarausfall bewegen sollte, muss nun definitiv bestimmt werden, doch wird der Wert bei normaler BSG (Blutsenkungsgeschwindigkeit, NW: < 10 mm/h) ungefähr bei 70 µg/l liegen. Auch die essentielle Aminosäure L‐Lysin scheint beim Haarausfall relevant zu sein. Eine Doppelblind‐Studie bestätigte die Ergebnisse einer offenen Studie an Frauen mit vermehrtem Haarausfall, von denen viele gut auf die Gabe von L‐Lysin und Eisensubstitution reagierten. Es gibt keine Beweise für die verbreitete Meinung, dass niedrige Serum‐Zink‐Spiegel Haarausfall begünstigen. Die exzessive Einnahme von Ernährungsergänzungsmitteln kann sogar akuten Haarausfall verursachen und sollte ohne nachgewiesenen Mangel nicht erfolgen.Ernährungsfaktoren betreffen das Haar direkt, doch darf man nicht vergessen, dass sie auch die Haut betreffen. Bei Patienten mit Haarausfall sollten Haut‐ und Kopfhautschuppenbildungen abgeklärt werden, Ratschläge für eine vernünftige Haarpflege sind sinnvoll, und der Haarzyklus sollte dem Patienten ebenfalls geläufig sein. Viele Betroffenen waschen ihre Haare, aus der Angst heraus, mehr Haare zu verlieren, sehr selten, verlieren aber dann bei den selteneren Haarwäschen jeweils mehr Haare, was ihre Angst, kahl zu werden nur noch verstärkt und ihre Lebensqualität deutlich einschränkt.
Supportive Immunglobulingabe beim metastasierten Melanom unter Polychemoimmuntherapie nach dem „Legha‐Protokoll”
Authors: Fischer B. , Knop J. , Enk A. H.
Published: March 2003

Zusammenfassung: Hintergrund und Fragestellung: Das metastasierte maligne Melanom im Stadium IV hat als einer der aggressivsten Tumoren mit der Polychemoimmuntherapie nach dem sogenannten „Legha‐Protokoll” (5 – 7) eine vielversprechende Therapieoption erhalten. Angesichts der relativ hohen Toxizität dieses Therapieregimes, insbesondere der hohen Infektionsrate von 49 % (8), entschlossen wir uns zur begleitenden intravenösen Gabe von IgM‐angereicherten Immunglobulinen zur Infektionsprophylaxe.

 Patienten/Methoden: Von 1998 bis Anfang 2002 wurden insgesamt 34 Patienten mit einem metastasierten Melanom mittels Polychemoimmuntherapie nach dem Legha‐Protokoll behandelt und nachbeobachtet. Etwa vier Tage nach Abschluss des zweiten Zyklus der Polychemoimmuntherapie sowie nach jedem weiteren Zyklus erhielten die Patienten jeweils IgM‐angereicherte Immunglobuline intravenös verabreicht (5 ml/kg KG entsprechend 250 mg/kg KG).

 Ergebnisse: Von 34 behandelten Patienten erlitten drei Patienten Infektionen verschiedener Art:

 Ein Patient zeigte nach jedem Zyklus einen Herpes labialis, eine Patientin entwickelte nach dem dritten Zyklus einen Abszess im Bereich des rechten Unterarms und ein weiterer Patient hatte bereits nach dem ersten Zyklus, d. h. vor Anwendung der Pentaglobin‐Infusionen, einen glutealen Abszess. Mit nur 8,8 % ist damit die Rate der infektiösen Nebenwirkungen der Legha‐Therapie in Kombination mit einer begleitenden Immunglobulingabe deutlich geringer als die in der Literatur beschriebene Infektionsrate von 49 %.

 Schlussfolgerungen: Die begleitende Gabe von IgM‐angereicherten Immunglobulin während der Durchführung einer Polychemoimmuntherapie nach Legha kann die Rate von opportunistischen Infektionen in diesem sekundär immunsupprimierten Krankheitsklientel deutlich verringern.
Calcineurin‐Hemmer und Sirolimus: Wirkmechanismen und Anwendung in der Dermatologie
Authors: Reynolds N.J. , Al‐Daraji W.I.
Published: March 2003

Zusammenfassung: Kontrollierte Studien und klinische Erfahrungen geben Hinweise darauf, dass systemisch angewendetes Ciclosporin A und Tacrolimus wirksame Therapien der Psoriasis sind und dass Ciclosporin A auch zur Besserung bei atopischem Ekzem führt. Eine Reihe weiterer entzündlicher und nichtentzündlicher Hauterkrankungen sprechen vermutlich ebenfalls auf diese Medikamente an. Die weit verbreitete und langfristigere Anwendung von Ciclosporin A und Tacrolimus ist jedoch durch Nebenwirkungen eingeschränkt. Die molekularen Wirkungsmechanismen von Ciclosporin A, Tacrolimus und einem verwandten Medikament, Sirolimus, wurden gut belegt. Sie finden in den T‐Zellen statt und umfassen die Hemmung kritischer signalgebender Bahnen, welche die T‐Zell‐Aktivierung regulieren. Beispielsweise hemmen Ciclosporin und Tacrolimus die Calcineurin‐Phosphatase‐Aktivität und somit die Aktivierung des Transkriptionsfaktors NFAT. Die therapeutische Effektivität von lokal angewendeten Calcineurin‐Inhibitoren bei atopischem Ekzem hat das Interesse am Wirkungsmechanismus dieser Medikamente bei Hauterkrankungen neu entfacht. Kürzlich hat sich gezeigt, dass das Expressionsmuster von Calcineurin und NFAT in nicht zum Immunsystem gehörenden Geweben wie der Haut liegt. Die Relevanz dessen für den Wirkungsmechanismus von systemisch und lokal angewendeten Calcineurin‐Inhibitoren und Sirolimus bei Hauterkrankungen wird diskutiert.
Die Zytokin‐Blocker in der Dermatologie
Authors: Williams J.D.L. , Griffiths C.E.M.
Published: March 2003

Zusammenfassung: Zytokine sind interzelluläre Botenstoffe mit besonderer Bedeutung für die Entstehung und den Verlauf kutaner Entzündungsreaktionen. Die vorrangige Stellung der Zytokine im Rahmen der kutanen Immunantwort macht sie zu besonders attraktiven Angriffspunkten für neue biologische Immunmodulatoren. Diese Therapieoption für die Behandlung von Hauterkrankungen steckt allerdings noch in den Kinderschuhen. Die Blockade von Tumor Nekrose Faktor (TNF)‐α durch Infliximab oder Etanercept jedoch hat sich, insbesondere bei der Behandlung der Psoriasis, als vielversprechend erwiesen. Aus eher anekdotischen Berichten geht hervor, dass diese Behandlungsform auch bei einer Reihe anderer dermatologischer Krankheitsbilder wie dem Pyoderma gangraenosum und dem M. Beh et Wirkung gezeigt hat. Wir berichten über die gegenwärtige und zukünftige Bedeutung der Zytokin‐Blocker für die Behandlung von Hauterkrankungen.
Die Zukunft von Impfungen als Therapiestrategie bei dermatologischen Erkrankungen
Authors: Sterry W. , Walden P.
Published: March 2003

Zusammenfassung: Neue Entwicklungen in der Immunologie werden zunehmend und unmittelbarer für die Entwicklung von Impfstrategien zur Prävention oder Therapie von infektiösen, allergischen, autoimmunen und malignen Hauterkrankungen verwendet. Obwohl nahezu alle dieser neuen Konzepte sich noch immer in den Frühstadien der Entwicklung befinden und die klinischen Studien, die zur Untersuchung ihrer therapeutischen Wirksamkeit durchgeführt wurden, ihre experimentelle Natur zeigen, ist es vorhersehbar, dass Impfungen eine bedeutende Therapiemöglichkeit für diese Erkrankungen werden. Trotz vieler Versager können initiale Erfolge in vielen Einzelfällen als Boten künftiger Durchbrüche angesehen werden. Es sind noch immer viele Probleme zu lösen, die neuen Entwicklungen rechtfertigen jedoch rationale und systematische Ansätze für präventive sowie therapeutische Impfstoffe. Da es keine oder nur eingeschränkte Alternativen für die Therapie vieler dieser Erkrankungen gibt, gibt es hohe und, angesichts des gegenwärtigen Stands und der Richtungen von Forschung und Entwicklung neuer Impfstoffe, berechtigte Hoffnungen für viele Haut‐ sowie andere Erkrankungen, die mit Impfansätzen assoziiert sind.
Traditionelle Therapien: Glukokortikoide, Azathioprin, Methotrexat, Hydroxyharnstoff
Authors: Belgi G. , Friedmann P.S.
Published: March 2003

Zusammenfassung: Die „alten Favoriten”, die zur Therapie entzündlicher Erkrankungen verwendet wurden, und somit die ursprünglichen Immunmodulatoren sind, umfassen Glukokortikoide, Azathioprin, Methotrexat und Hydroxyharnstoff. Glukokortikoide zählen noch immer zu den wirksamsten antiphlogistischen Medikamenten, da sie mehrere unterschiedliche intrazelluläre Vorgänge beeinflussen und somit viele Komponenten hemmen, die an Entzündungs‐ und Immunreaktionen beteiligt sind. Sie binden sich an intrazelluläre Glukokortikoid‐Rezeptoren, welche sie in den Kern transportieren. Hier kann sich der Rezeptor/Steroid‐Komplex an viele Gene binden, die Glukokortikoid‐Response‐Elements in ihrer Promoter‐Region enthalten. Der Komplex kann mit Transkriptionsfaktoren wie NFκB und AP‐1 in Wechselwirkung treten und deren Aktivierung hemmen, wodurch die Aktivierung vieler Gene gehemmt wird, die Immun‐Effektor‐ und proinflammatorische Zytokine kodieren. Proteinkinasen, die an der intrazellulären Signalgebung beteiligt sind, werden ebenfalls direkt aktiviert, was zur Phosphorylierung verschiedener Zielmoleküle führt. Unter ihnen ist Annexin (AXA)‐1 von erheblicher Bedeutung zur Hemmung der Bildung von Prostaglandinen. Die Wirkung von Azathioprin verläuft völlig anders. Es hemmt die Biosynthese sowohl der Purine als auch der DNS. Dies führt zu einer verringerten Proliferation von B‐ und T‐Lymphozyten, verringerten Immun‐Effektor‐Mechanismen und verringerter Rekrutierung von mononukleären Zellen wie Monozyten im Bereich entzündlicher Reaktionen. Methotrexat blockiert ebenfalls die DNS‐Synthese und somit die Zellproliferation, induziert jedoch gleichzeitig die Freisetzung von Adenosin. Das hemmt die Chemotaxis polymorphkerniger Neutrophiler und die Freisetzung wesentlicher Zytokine wie TFN‐α und Interleukine 6 und 8. Hydroxyharnstoff hemmt ebenfalls die DNS‐Synthese und hat inhibitorische Wirkungen auf die Proliferation von Lymphozyten und möglicherweise Keratinozyten.  Auch wenn viele neue Substanzen mit erheblich größerer Selektivität zur klinischen Anwendung gelangen, hat diese Gruppe alter Medikamente noch immer eine absolut zentrale Stellung in der Gruppe der verwendeten Substanzen. Ihre Bedeutung liegt in der Tatsache, dass sie keine „clean drugs” mit engem Wirkungsbereich sind, sondern eine Reihe von Mechanismen hemmen, die an Immun‐ und Entzündungsvorgängen beteiligt sind.