Molecular phylogeny of Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (Monogenoidea: Dactylogyridae), gill parasites of Neotropical catfishes (Siluriformes).

Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (Dactylogyridae) represents one of the most species-rich groups (22 species currently recognized as valid) of all dactylogyrid parasites infecting Neotropical catfishes. Species of Cosmetocleithrum exhibit a remarkable affinity towards catfishes of the Doradidae and the Auchenipteridae. However, phylogenetic relationships between members of this genus have not been yet analysed. This study analysed newly obtained partial sequences of the 28S ribosomal RNA gene of seven species of Cosmetocleithrum, including its type species C. gussevi Kritsky, Thatcher & Boeger, 1986, along with several other dactylogyrids infecting siluriform, gymnotiform, perciform and characiform fishes. Cosmetocleithrum appeared as an evolutionary recent group, composed of two well-defined lineages: lineage 1 includes parasites of doradids - namely, C. bulbocirrus, C. confusum, C. parvum and C. bifurcum - whereas lineage 2 is composed of species from doradids - that is, C. rarum, C. gussevi, C. gigas, C. trachydorasi and C. falsunilatum - together with parasites of auchenipterids - namely, C. laciniatum and C. baculum. The search for synapomorphies to characterize taxonomic groups within Cosmetocleithrum appears challenging, since the morphology of their haptoral elements is quite conservative, and that of the copulatory complex is highly variable between species. The results of the present study support the recent synonymization of Paracosmetocleithrum Acosta, Scholz, Blasco-Costa, Alves & Silva, 2018 with Cosmetocleithrum. Whereas the 28S ribosomal DNA data resolved Cosmetocleithrum as monophyletic, the statistical support for the lineage was low, rendering its phylogenetic position between other Neotropical dactylogyrids yet undefined.

A new genus of caryophyllidean tapeworms (Cestoda) from Mystus catfishes (Bagridae) in India: cleaning up taxonomic chaos.

A new genus, Mystocestus, is proposed to accommodate a new species, Mystocestus anindoi n. g., n. sp. from Mystus vittatus (Bloch) (type host) in West Bengal and Mystus cavasius (Hamilton) (Siluriformes: Bagridae) in Maharashtra, India. The new genus is most similar to Lucknowia Gupta, 1961 in the shape of the body, which is elongate, slightly tapering towards the anterior end, and scolex, which is digitiform, but differs in the shape of the ovary, which is H-shaped (vs. inverted A-shaped in Lucknowia), the absence of a seminal receptacle (present in Lucknowia) and exclusively cortical vitelline follicles (vs. some follicles in the medulla in the latter genus). Molecular data support the erection of the new genus and place it close to Bovienia Fuhrmann, 1931, species of which can be easily distinguished by exclusively lateral vitelline follicles (lateral and median in the new genus), the presence of a seminal receptacle (absent in Mystocestus) and scolex shape (digitiform, with blunt or slightly concave anterior edge in the new genus vs. small, unspecialized or spatulate in Bovienia). The convoluted taxonomy of tapeworms placed in Mystoides Mathur, 1992 is critically reviewed to clean up taxonomic chaos in Indo-Malayan caryophyllideans. Mystoides was erected in an unpublished PhD thesis and thus its generic name becomes unavailable and also, its type species is conspecific with Lucknowia fossilisi Gupta, 1961 from the stinging catfish, Heteropneustes fossilis (Bloch). Other species of this genus are also conspecific with L. fossilisi. In addition, specific names of most of these taxa are unavailable because they were described in unpublished theses or conference abstracts. Based on recent revisions of Indo-Malayan caryophyllideans, the following nine genera with 15 species are considered valid (numbers of species of individual genera are provided in parentheses): Bovienia (3), Djombangia (1), Lucknowia (2), Lytocestus (2), Mystocestus (1), Pseudocaryophyllaeus (2) (all family Lytocestidae); Adenoscolex (1), Lobulovarium (2), Paracaryophyllaeus (1) (all family Caryophyllaeidae).

High diversity of metazoan parasites in carp gudgeons (Eleotridae: Hypseleotris spp.) from Eastern Australia.

Knowledge of the parasite fauna of Australian freshwater fish is fragmentary and incomplete. An understanding of fish hosts and their associated parasites is vital for the successful management of aquatic ecosystems. In this study, we surveyed the parasite fauna of carp gudgeons (Hypseleotris spp.), a complex of species of Australian freshwater fishes, using morphology and molecular data for the 18S and 28S ribosomal RNA genes. We examined 137 individuals of three different taxa in the carp gudgeon species complex and found 16 parasitic taxa of the Digenea, Cestoda, Nematoda and Arthropoda (five adults and 11 larvae). Eleven parasites are reported for the first time from the carp gudgeons (Pseudodactylogyrus sp., Gyrodactylus sp., Clinostomum sp., Paradilepis patriciae, P. cf. kempi, two unidentified species of Paradilepis, Dendrouterina sp., Parvitaenia sp., two lineages of Cyclophyllidea gen. sp., Procamallanus sp., larvae of a spirurine nematode and Lernaea sp.), in addition to Apatemon cf. hypseleotris Negm-Eldin & Davies, 2001 and the invasive tapeworm Schyzocotyle acheilognathi (Yamaguti, 1934), which were previously reported from these fish hosts. Parasite species richness was double in Lake's and Midgley's carp gudgeons relative to western carp gudgeon. These findings highlight the key role of carp gudgeons as intermediate hosts for multiple parasites with complex life cycles using native birds as definitive hosts and the usefulness of DNA data for the identification of parasite larvae.

Redescription of Acanthogyrus (Acanthosentis) maroccanus (Dollfus, 1951) (Acanthocephala: Quadrigyridae), a parasite of the Algerian barb Luciobarbus callensis (Valenciennes) (Cyprinidae) in Algeria, and first molecular data.

Acanthogyrus (Acanthosentis) maroccanus (Dollfus, 1951), an insufficiently described quadrigyrid acanthocephalan of cyprinid fishes from Northwest Africa, is redescribed based on recently collected specimens from the Algerian barb Luciobarbus callensis (Valenciennes) in Algeria. Newly observed morphological features for A. (A.) maroccanus include the arrangement of proboscis hooks (not in regular circles), the male reproductive structures extending into the copulatory bursa and the presence of a para-receptacle structure and vaginal sleeve. The mechanism of copulation of this acanthocephalan is described based on several copulating pairs. The phylogenetic position of A. (A.) maroccanus within Eoacanthocephala was assessed based on partial 28S rDNA sequences. Maximum likelihood and Bayesian inference analyses placed A. (A.) maroccanus in a clade with Palliolisentis (Demidueterospinus) ophiocephalus (Thapar, 1931), both species included in the Quadrigyridae, the only family within the Gyracanthocephala.

The First Record of the Invasive Asian Fish Tapeworm (Schyzocotyle Acheilognathi) from An Endemic Cichlid Fish in Madagascar.

The Asian fish tapeworm, Schyzocotyle acheilognathi (Yamaguti, 1934) (Cestoda: Bothriocephalidea), is an invasive parasite of freshwater fishes that have been reported from more than 200 freshwater fish worldwide. It was originally described from a small cyprinid, Acheilognathus rombeus, in Japan but then has spread, usually with carp, minnows or guppies, to all continents including isolated islands such as Hawaii, Puerto Rico, Cuba or Sri Lanka. In the present account, we report the first case of the infection of a native cichlid fish, Ptychochromis cf. inornatus (Perciformes: Cichlidae), endemic to Madagascar, with S. acheilognathi. The way of introduction of this parasite to the island, which is one of the world's biodiversity hotspots, is briefly discussed.

Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries.

Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 µmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the "sickest children first" allocation policy and correction of malnutrition before surgery.

CDK9 inhibition as an effective therapy for small cell lung cancer.

Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC.

Early implant healing: promotion of platelet activation and cytokine release by topographical, chemical and biomimetical titanium surface modifications in vitro.

OBJECTIVES: Platelet releasate has been shown to promote osteogenetic cell proliferation and differentiation. Topography and chemistry of biomaterials have high impact on platelet activation. More specifically, the bioactive cell adhesive peptide sequence Arg-Gly-Asp (RGD) triggers platelet activation mediated by the α(IIb) ß(3) integrin receptor. Accordingly, topographical, chemical and biomimetical (immobilized RGD peptide) modifications of titanium (Ti) surfaces may enhance early platelet activation and bony healing of implants. Therefore, the aim of the study was to evaluate platelet activation with subsequent platelet-derived cytokine release by accordingly modified Ti surfaces. MATERIALS AND METHODS: Pre-treated (PT; mean roughness [R(a)]=0.04 µm, contact angle [CA]=91°), acid-etched (A, R(a) =0.83 µm, CA=106°), large grit-sandblasted, acid-etched (SLA, R(a) =3.2 µm, CA=109°) as well as hydrophilically modified acid-etched (modA, R(a) =0.83 µm, CA=0) and modified large grit-sandblasted, acid-etched (modSLA, R(a) =3.2 µm; CA=0°) titanium surfaces were investigated. Additionally, RGD peptides were chemically immobilized on PT, A and SLA surfaces (PT-RGD [CA=18°], A-RGD [CA=0°], SLA-RGD [CA=0°]). The different Ti surfaces were incubated with platelet concentrate of three healthy volunteers at room temperature for 15 min and for 30 min. High thrombogenous collagen served as the control group. Out of the supernatant, platelet consumption was assessed via platelet count (PC). Cytokine release was quantified via the level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). RESULTS: After 15 min, especially the rough SLA surface showed a strong decrease in PC and a strong increase in VEGF and PDGF levels. After 30 min, high platelet consumption as well as high levels of VEGF and PDGF were measured for unspecifically modified (modA) and especially for biomimetic, specifically modified (PT-RGD, A-RGD) surfaces, indicating a delayed effect of the surface modifications on platelet activation. DISCUSSION: Modifications of surface roughness modifications appear to influence early platelet activation and cytokine release after 15 min whereas surface chemistry modifications with increased hydrophilic properties and surface modifications via RGD peptide on plainer surfaces lead to a further, more specific promotion of platelet activation and degranulation after 30 min. The observed effect could be valuable for critical clinical situations like compromised bone sites.

Larval gryporhynchid tapeworms (Cestoda: Cyclophyllidea) of British freshwater fish, with a description of the pathology caused by Paradilepis scolecina.

Larvae of the cyclophyllidean tapeworms Paradilepis scolecina (Rudolphi, 1819), Neogryporhynchus cheilancristrotus (Wedl, 1855) and Valipora campylancristrota (Wedl, 1855), are described from British freshwater fish. The morphometrics of the rostellar hooks, infection characteristics and host ranges of these parasites from fisheries in England and Wales are presented. Difficulties in the detection, handling and identification of these tapeworms are highlighted, and may in part explain the paucity of records from Britain. Tissue digestion was shown to be a useful technique for the examination of these parasites, providing clear and consistent preparations of the rostellar hooks for measurement. The pathological changes caused by P. scolecina to the liver of wild tench, Tinca tinca, are detailed for the first time. Tapeworms located in the hepatic parenchyma and pancreatic tissues caused little pathological damage and invoked only mild inflammatory responses. The small size of these tapeworms and their encapsulation within host tissues appear to limit the severity of pathology, compared with parasites that insert their rostellum during attachment.

Processive behaviour of kinesin observed using micro-fabricated cantilevers.

The mechanical characterization of biomolecular motors requires force sensors with sub-piconewton resolution. The coupling of a nanoscale motor to this type of microscale sensors introduces structural deformations in the motor according to the thermally activated degrees of freedom of the sensor. At present, no simple solution is available to reduce these effects. Here, we exploit the advantages of micro-fabricated cantilevers to produce a force sensor with essentially one degree of freedom and a spring constant of 0.03 pN nm(-1) for the study of the molecular motor protein kinesin-1. During processive runs, the cantilever constrains the movement of the cargo binding domain of kinesin in a straight line, parallel to the microtubule track, and excludes specific reaction coordinates such as cargo rotation. In these conditions, we measured a step size of 8.0 ± 0.4 nm and a maximal unloaded velocity of 820 ± 80 nm s(-1) at saturated adenosine triphosphate (ATP) concentration. We concluded that the motor does not need to rotate its tail as it moves through consecutive stepping cycles.

Parasites in a man-made landscape: contrasting patterns of trematode flow in a fishpond area in Central Europe.

We have explored a large body of novel data focusing on small-scale temporal and spatial patterns in the composition and structure of larval trematode communities in Lymnaea stagnalis (L.) from a typical Central European agricultural landscape. The 5 eutrophic fishponds studied provide excellent environments for the development of species-rich and abundant trematode communities. Nine prevalent species were consistently present in component communities, but had differential contribution to the parasite flow in the 5 ponds resulting in significant contrasting patterns of community similarity and the prevalence of the 3 major transmission guilds driving this similarity. Component communities split into 2 groups: (i) those from the large pond dominated by anatid and larid generalists with active miracidial transmission; and (ii) those from the smaller ponds dominated by 2 plagiorchioideans infecting snails via egg ingestion. We put forward 3 hypotheses for the remarkable differences in larval trematode flow in the similar and closely located eutrophic ponds: (i) species-specific differences in parasite colonization potential displayed by an 'active-passive' dichotomy in miracidial transmission strategies of the species; (ii) top-down effects of pond context on transmission pathways of the trematodes; and (iii) competition as an important mechanism in eutrophic environments with a bottom-up effect on component community structure.

Histopathological and ultrastructural studies of the tapeworm Monobothrium wageneri (Caryophyllidea) in the intestinal tract of tench Tinca tinca.

Monobothrium wageneri is a monozoic caryophyllidean tapeworm of tench Tinca tinca. The pathological changes caused by this parasite within the intestinal tract of wild tench are described for the first time. Parasites were found attached to the anterior third of the intestine in tight clusters comprising up to 109 tapeworms. Infection was associated with the formation of raised inflammatory swellings surrounding the parasites. This host response, combined with the deep penetration of the scolex into the gut wall, formed a very firm seat of parasite attachment. Histopathological changes were characterised by a pronounced fibrogranulomatous lesion that extended through all layers of the intestine. This was accompanied by haemorrhage, oedema, necrosis and degeneration of the muscularis. A marked eosinophilic interface layer between the scolex of the tapeworm and gut wall indicated intimate host-parasite contact. Ultrastructural examinations revealed coniform spinitriches covering the neck and lateral sides of the scolex and capilliform filitriches present on the apical end of the scolex. Numerous glandular cytons (tegumental glands) were recorded throughout the scolex tegument. Large numbers of secretory granules discharged from the glands through a network of processes onto the scolex surface were consistent with distancing the cellular responses of the host. Observations of severe inflammatory lesions, partial intestinal occlusion and the potential for intestinal perforation represent important pathological changes that are consistent with loss of normal gut function. The lesions associated with the attachment of M. wageneri are more severe than those recorded for any other tapeworm of British freshwater fish.

Predicting neurodevelopmental impairment in preterm infants by standardized neurological assessments at 6 and 12 months corrected age.

AIM: Neurodevelopmental impairment in very preterm infants can be reasonably diagnosed by 18-24 months corrected age, whereas the predictive value of earlier assessments is debated. We hypothesized that neurological findings at 6 and 12 months indicative of subsequent cerebral palsy predict 18-24 months' neurodevelopmental impairment. METHODS: Neurodevelopmental examinations (Griffiths scales) at 20 months of age in 561 preterm infants (birth weight <1 500 g) were compared with results of standardized neurological examinations (Early Motor Pattern Profile; EMPP) and Griffiths scales at 6 (n = 451) and 12 months (n = 496) corrected age. RESULTS: Griffiths developmental quotients at 20 months were weakly but significantly related to EMPP scores at 6 (R(s) = 0.328) and 12 months (R(s) = 0.493). Areas under receiver operator characteristic curves for the EMPP to predict neurodevelopmental impairment (Griffiths scores

Interplay of host specificity and biogeography in the population structure of a cosmopolitan endoparasite: microsatellite study of Ligula intestinalis (Cestoda).

Organisms with wide geographical or phenotypic diversity often constitute assemblages of genetically distinct species or lineages. Within parasites, an emergence of host-specific lineages is assumed to create such cryptic variability; however, empirical evaluation of these processes is scarce. Here, we analyse populations of a parasite with a complex life cycle, wide host spectrum and global distribution, with the aim to reveal factors underlying the evolution of host- or geography-dependent lineages. Using 15 microsatellite loci, deep genetic distances were observed between populations from distant geographical areas. On the local scale, host-mediated genetic structure was found among sympatric samples. Two lineages differing in the spectrum of infected hosts co-occurred in the Euro-Mediterranean area, and two distinct lineages were recovered from Lake Tana in Ethiopia. Although sampled across several host taxa and multiple localities, a lack of marked genetic structure was seen in the populations belonging to one of the European lineages. Only weak genetic differentiation between sympatric samples from two host species was found. Complexity of the parasite life-cycle contributed to such a stratified pattern. Differences in the immune response between fish hosts were suggested as the factor diversifying the populations locally; conversely, high mobility of the parasite due to migration with its bird (definitive) host were assessed to homogenize populations across the area of distribution. However, despite the high mobility, large bodies of salt water prevent the parasite from long-distance migrations, as was demonstrated in an example of the Mediterranean Sea which represented an effective barrier to gene flow.

Lung hyperinflation: foe or friend?

Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

Suppression of the tapeworm order Pseudophyllidea (Platyhelminthes: Eucestoda) and the proposal of two new orders, Bothriocephalidea and Diphyllobothriidea.

Pseudophyllidea van Beneden in Carus, 1863, a well recognised order of tapeworms (Platyhelminthes: Eucestoda), is suppressed because it is composed of two phylogenetically unrelated groups, for which the new names Bothriocephalidea and Diphyllobothriidea are proposed. The new orders differ from each other in the following characters: (i) position of the genital pore: on the dorsal, dorso-lateral or lateral aspects and posterior to the ventral uterine pore in the Bothriocephalidea versus on the ventral aspect of segments and anterior to the uterine pore in the Diphyllobothriidea; (ii) the presence of a muscular external seminal vesicle in the Diphyllobothriidea, which is absent in the Bothriocephalidea; (iii) the presence of a uterine sac in the Bothriocephalidea, which is absent in the Diphyllobothriidea; and (iv) the spectrum of definitive hosts: mainly teleost fishes, never homoiothermic vertebrates in the Bothriocephalidea, versus tetrapods, most frequently mammals, in the Diphyllobothriidea, with species of Diphyllobothrium, Spirometra and Diplogonoporus parasitic in humans. The Diphyllobothriidea, which includes 17 genera in four families (Digramma is synonymised with Ligula), is associated with cestode groups that have a range of plesiomorphic characters (Haplobothriidea and Caryophyllidea), whereas the Bothriocephalidea, consisting of 41 genera grouped in four families, is the sister-group to the 'acetabulate' or 'tetrafossate' cestodes, which are generally regarded as having derived characters.

On the position of Archigetes and its bearing on the early evolution of the tapeworms.

The tapeworm Archigetes sieboldi Leuckart, 1878 (Platyhelminthes: Cestoda: Caryophyllidea) has been cited as a likely representative of the "protocestode" condition, owing to its lack of segmentation and ability to attain sexual maturity in the invertebrate host (aquatic oligochaetes). The idea has been variously amplified or rejected in the literature, although the actual phylogenetic position of the species has not been investigated until now. New collections of Archigetes sp. from both its vertebrate and invertebrate hosts provided the opportunity to estimate its phylogenetic position with the use of molecular systematics, while prompting new analyses aimed at assessing the early diversification of the Cestoda. Additional collections representing the Amphilinidea, Caryophyllidea, and Gyrocotylidea were combined with published gene sequences to construct data sets of complete 18S (110 taxa) and partial (D1-D3) 28S (107 taxa) rDNA sequences, including 8 neodermatan outgroup taxa. Estimates resulting from Bayesian inference, maximum likelihood, and maximum parsimony analyses of the separate and combined data sets supported a derived position of the genus within the Caryophyllidea, and thus reject the idea that Archigetes sp. may exemplify a "primitive" condition. Topological constraint analyses rejected the hypothesis that Archigetes represents the most basal lineage of the Eucestoda, but did not rule out that it could represent the earliest branching taxon of the Caryophyllidea. In all analyses, the Eucestoda were monophyletic and supported basal positions of the nonsegmented Caryophyllidea and Spathebothriidea relative to other major lineages of the Eucestoda, implying that segmentation is a derived feature of the common ancestor of the di- and tetrafossate eucestodes. However, constraint analyses could not provide unequivocal evidence as to the precise branching patterns of the cestodarian, spathebothriidean, and caryophyllidean lineages. Phylogenetic analyses favor the interpretation that sexual maturity of Archigetes sp. in the invertebrate host, and similar examples in members of the Spathebothriidea, are the result of progenesis and have little if any bearing on understanding the protocestode condition.

[Cost analysis of conservative versus operative therapy of macromastia]. / Kostenanalyse der konservativen versus operativen therapie der makromastie.

Macromastia causes back and neck pain, scaphodynia, intertrigo of the inframammary crease up to dysaesthesia. Typical complaints of patients with macromastia are physical burden, psychological irritation and aesthetic deformity, often resulting in social isolation. Despite the demonstrable success of reduction mammaplasty to eliminate not only the symptoms of macromastia but the cause of the ailment, conservative therapy is still favoured by insurance companies and bearing of costs for surgical therapy therefore is rejected. Expenses of conservative treatment as well as costs related to appeal and lawsuits against insurance decisions exceed the case-based lump sum of reduction mammaplasty manifold. Conservative treatments do not eliminate the causes of the illness. Therefore the rejection of a medically indicated reduction mammaplasty has to be regarded as unfavourable and economically inefficient.

[The oculocardiac reflex in blepharoplasties]. / Der okulokardiale Reflex bei Blepharoplastiken.

The oculocardiac reflex (OCR) is a well-known phenomenon in ophthalmic surgery, but is rarely described in aesthetic blepharoplasty surgery. It was first mentioned in 1908 by Ascher and Dagnini. Since then, ophthalmologists and anaesthesiologists have regarded the onset of the oculocardiac reflex as a significant intraoperative problem, which is undermined by several case reports that describe dysrhythmias which have haved caused morbidity and death. Per definition the OCR is caused by ocular manipulation and involves intraoperative bradycardia by a change of 20 beats/minute compared to the preoperative heart rate or any dysrhythmia during the manipulation via a trigeminal-vagal-mediated reflex arc. Having operated on a 48-year-old, healthy woman in our clinic, who underwent a cardiac arrest during the blepharoplasty procedure, followed by a successful resuscitation, we investigated the onset of the OCR in our blepharoplasty patients within the last 3 years. The onset of the OCR was noted in 22 of 110 (20 %) blepharoplasty patients, mainly affecting younger, low-weighted patients operated under local anaesthesia. Awareness and treatment of this potentially life-threatening oculocardiac reflex are necessary. In most cases the onset of the reflex may be avoided by a gentle operation technique and by refraining from severe traction to the muscle or fat pad. The best treatment of a profound bradycardia caused by the OCR is to release tension to the muscle or fat pad in order to permit the heart rate to return to normal. Intraoperative monitoring is of utmost importance.

Diagnostic management of benign and malignant pheochromocytoma.

As rare and thus often overlooked hormone-secreting tumors, pheochromocytomas pose a particular diagnostic challenge. Difficulties involve biochemical confirmation, localizing, and detection of malignancy. Measurement of free plasma metanephrines, genetic testing and specific imaging procedures--such as MIBG and octreotide scintigraphy or fluorodopamine PET--represent a considerable progress, and the management of benign pheochromocytomas has become very effective. However, a comparable improvement in the prognosis of malignant chromaffin cell tumors, which occur in approximately 10-15% of all cases, has not yet been achieved. Here, telomerase catalytic subunit (hTERT) activity and heat shock protein 90 expression could serve both as molecular markers allowing an earlier diagnosis of malignancy and as therapeutic targets. Familial syndromes should be considered both in benign and malignant pheochromocytoma, and should be tested for prior to surgery in selected patient groups.