Phylogenetic signal in bone microstructure of sauropsids.

In spite of the fact that the potential usefulness of bone histology in systematics has been discussed for over one and a half centuries, the presence of a phylogenetic signal in the variation of histological characters has rarely been assessed. A quantitative assessment of phylogenetic signal in bone histological characters could provide a justification for performing optimizations of these traits onto independently generated phylogenetic trees (as has been done in recent years). Here we present an investigation on the quantification of the phylogenetic signal in the following bone histological, microanatomical, and morphological traits in a sample of femora of 35 species of sauropsids: vascular density, vascular orientation, index of Haversian remodeling, cortical thickness, and cross-sectional area (bone size). For this purpose, we use two methods, regressions on distance matrices tested for significance using permutations (a Mantel test) and random tree length distribution. Within sauropsids, these bone microstructural traits have an optimal systematic value in archosaurs. In this taxon, a Mantel test shows that the phylogeny explains 81.8% of the variation of bone size and 86.2% of the variation of cortical thickness. In contrast, a Mantel test suggests that the phylogenetic signal in histological traits is weak: although the phylogeny explains 18.7% of the variation of vascular density in archosaurs, the phylogenetic signal is not significant either for vascular orientation or for the index of Haversian remodeling. However, Mantel tests seem to underestimate the proportion of variance of the dependent character explained by the phylogeny, as suggested by a PVR (phylogenetic eigenvector) analysis. We also deal with some complementary questions. First, we evaluate the functional dependence of bone vascular density on bone size by using phylogenetically independent contrasts. Second, we perform a variation partitioning analysis and show that the phylogenetic signal in bone vascular density is not a by-product of phylogentic signal in bone size. Finally, we analyze the evolution of cortical thickness in diapsids by using an optimization by squared change parsimony and discuss the functional significance of this character in terms of decreased buoyancy in crocodiles and mass saving in birds. These results are placed in the framework of the constructional morphology model, according to which the variation of a character in a clade has a historical (phylogenetic) component, a functional (adaptive) component, and a structural (architectural) component.

Relationship between bone growth rate and the thickness of calcified cartilage in the long bones of the Galloanserae (Aves).

The histological features of mineralized tissues can be preserved for hundreds of millions of years, and are therefore important potential sources of information for reconstructing the life history traits of extinct species. Bone growth rates and the duration of the growth period have recently been estimated in fossil archosaurs from periosteal ossification (a mechanism responsible for bone diametral growth). Similarly, data on endochondral ossification (the mechanism responsible for bone longitudinal growth) may also yield information on growth duration and rate among extinct vertebrates, as long as potentially informative structures are preserved. However, in order to carry out palaeobiological estimations of growth rate and/or the duration of growth, it is first necessary to quantify in extant species the relationship between these life history traits and the histological features of endochondral ossification that are potentially preserved in the fossil record. Here we analyse the ontogenetic variation of both bone longitudinal growth rate and the thickness of the calcified cartilage in the femora of two Galloanserae (Aves) and find a significant positive relationship between these variables in both species. We discuss possible factors underlying interspecific differences in this relationship, and conclude that it could be applied with caution to draw palaeobiological inferences.

Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus).

Microstructure-function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones (humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3-5 weeks after hatching) and identified the associated bone tissue types ('laminar', 'longitudinal', 'reticular' or 'radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 microm day(-1) (mean 55 microm day(-1)). There was a highly significant relationship between bone tissue type and growth rate (P<10(-6)). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered (P<10(-5)) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.

Contribution of collagen stable isotope biogeochemistry to the paleobiology of extinct endemic vertebrates from Tenerife (Canary Islands, Spain).

The paleodiet and paleoenvironmental context of two extinct species from Tenerife island, one giant rat Canariomys bravoi and one giant lizard Gallotia goliath, have been investigated using carbon and nitrogen isotopic compositions of fossil bone collagen. Preliminary to this study, a calibration of the isotopic variations of bone collagen from modern Rat Rattus rattus, Rabbit Oryctolagus cuniculus and Lizard Gallotia galotti relative to environmental conditions on Tenerife Islands has been attempted. No clear relationship could be found between collagen delta13C and delta15N values and aridity; the only relevant factors seem to be seashore proximity for rat, and the relative amount of C3 and CAM plants. It seems that anthropic activities have interfered with the expected relationships between collagen isotopic compositions and environmental conditions. Most fossil specimens yielded well preserved collagen. The isotopic composition of giant rat and giant lizard collagen suggest a purely C3 environment, possibly more humid than today on Tenerife. Large ranges of nitrogen isotopic compositions, especially within giant rats, may be due to local environmental conditions. Further work is needed in order to provide more valuable paleobiological information in order to better understand the role of environmental factors in the evolution and extinction of insular endemic species on Tenerife.

Heterochronic detection through a function for the ontogenetic variation of bone shape.

Heterochrony, evolutionary modifications in the rates and/or the timing of development, is widely recognized as an important agent of evolutionary change. In this paper, we are concerned with the detection of this evolutionary mechanism through the analysis of long bone growth. For this, we provide a function sigma (t) for the ontogenetic variation of bone shape by taking the ratio of two Gompertz curves explaining, respectively, the relative contribution to long bone growth of (a) endochondral ossification and (b) periosteal ossification. The significance of the fitting of this function to empirical data was tested in Anas platyrhynchos (Anseriformes). In this function sigma (t), the time t(m) at which periosteal growth rate first equalizes endochondral growth rate was taken as the timing parameter to be compared between taxa. On the other hand, the maximum rate of ontogenetic change in bone shape (maximum slope, beta) from hatching to t(m) was taken as the rate parameter to be compared. Comparisons of these parameters between the plesiomorphic condition and the derived character state would provide evidence for hypomorphosis (earlier occurrence of t(m)), hyper-morphosis (delayed occurrence of t(m)), deceleration (smaller beta) or acceleration (higher beta). Regarding the phylogenetic context, the ancestral condition for the character of interest should be estimated to polarize the direction of the heterochronic change. We have quantified the influence of the phylogenetic history on the variation of adult bone shape in a sample of 13 species of Anseriformes and 17 species from other neornithine orders of birds by using permutational phylogenetic regressions. Phylogenetic effects are significant, and this fact allows the optimization of bone shape onto a phylogenetic tree of Anseriformes to estimate the ancestral condition for Anas platyrhynchos.

[Cutaneous Waldenström's macroglobulinemia]. / Localisations cutanées de la maladie de Waldenström.

BACKGROUND: We report the case of a patient in whom the first manifestation of Waldenström' s macroglobulinemia was specific skin lesions, treated with chlorambucil chemotherapy. CASE REPORT: A 76-years old woman was referred to us because of chronic red nodular lesions on her face. A biopsy specimen showed a dense lymphocytic dermal infiltrate and immunohistochemistry identified a monoclonal B lymphoid population with an IgM-kappa phenotype. The patient's disease was diagnosed as Waldenström's macroglobulinemia with cutaneous localization, on the basis of a high level of circulating macroglobulinemia and a lymphoplasmocytic infiltrate in the bone marrow expressing the same monoclonal IgM-kappa as in blood and skin. Treatment with radiotherapy (12 Grays) was unsuccessful. Chlorambucil (16 mg per day, 7 days per month) was then introduced with rapid disappearance of the skin lesions. Neutropenia led to withdrawal of this treatment after 4 courses. The skin lesions relapsed 18 months later and were cured with chlorambucil at a lower dose. DISCUSSION: Specific skin infiltrates have been rarely described during Waldenström's macroglobulinemia. Review of the literature showed eight cases of such lesions treated by chemotherapy with only two successes with oral cyclophosphamide and polychemotherapy (cyclophosphamide, vincristine and CCNU). Chlorambucil was used unsuccessfully three times. We hypothesize that primary resistance to alkylating-agent and the small number of cases of cutaneous Waldenström's macroglobulinemia may explain the poor response to systemic chemotherapy previously reported.

Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.

The interstitial granulomatous drug reaction (IGDR) is a novel drug-associated entity, characterized by violaceous plaques with a predilection for skin fold areas. Light microscopically, it resembles the incipient diffuse interstitial phase of granuloma annulare. Differentiating light microscopic features include the absence of complete collagen necrobiosis, the presence of interface dermatitis, and variable lymphoid atypia. The lack of vasculitis rules out the extravascular necrotizing granuloma (Winkelmann granuloma) associated with systemic disease. The differential diagnosis with interstitial granulomatous dermatitis with arthritis as defined by Ackerman et al. has not been studied until now. Our aim was to determine the histologic criteria allowing us to differentiate IGDR without interface dermatitis and lymphoid atypia from interstitial granulomatous dermatitis. We report three patients with IGDR triggered, in two cases by respectively angiotensin convertin enzyme (ACE) inhibitors and furosemide, and in one case by the association of an ACE inhibitor, furosemide, and fluindione. Histologic examination showed a histological pattern of interstitial granulomatous dermatitis. We found a dense, diffuse histiocytic infiltrate distributed interstitially and in palisaded array within the reticular dermis. Eosinophils and some neutrophils were scattered throughout the infiltrate. In some tiny foci, enveloped by histiocytes, thick collagen bundles associated with basophilic nuclear debris or "flame figures" were seen. Vasculitis, interface dermatitis, or lymphoid atypia were absent. Our study allowed us to expand the histological spectrum of IGDR including a histological pattern similar to interstitial granulomatous dermatitis. The lack of degenerated collagen could be a subtle clue in favor of interstitial granulomatous dermatitis triggered by a drug.

Periosteal bone growth rates in extant ratites (ostriche and emu). Implications for assessing growth in dinosaurs.

The first quantitative experimental data on growth dynamics of the primary cortical bone of young ratites demonstrate the following. 1) From hatching to 2 months of age, cortical thickness remains constant, thereby expressing equilibrium between periosteal bone deposition and an endosteal bone resorption. 2) Radial growth rates of the diaphyseal bone cortex are high (10-40 microns.day-1 on average--maximum 80 microns.day-1) in the hindlimb (femur, tibiotarsus and tarsometatarsus). Wing bones are smaller and later developed. They have lower rates of radial osteogenesis (2-14 microns.day-1). 3) High growth rates are linked to densely vascularized primary bone belonging to the reticular or laminar tissue types. Growth rates fall when bone vascular density decreases. These results emphasize the importance of examining a large number of skeletal elements in order to build a precise knowledge of the general relationship between bone growth rate and bone tissue type. They also stress the potential of bone growth rate quantification among extinct tetrapods, including non-avian dinosaurs.

[Cheilitis granulomatosa in a child]. / Chéilite granulomateuse chez une enfant.

UNLABELLED: Granulomatous cheilitis is a rare disorder characterized by intermittent swelling of one or both lips, which may become persistent. We report a case occurring in a child, which improved with minocycline treatment. CASE REPORT: An eight year-old girl was seen for the swelling of her upper lip, which persisted for more than one year. There was no history of applied irritants, local trauma or atopy. On examination, the upper lip was swollen, indurated, erythematous and fissured with a bilateral perleche. The tongue and gums were normal. There was no facial palsy. The girl was in good health and did not take any drugs. Blood investigations were normal. Patch tests were negative. Antibiotic treatment or local steroids provided only temporary improvement. A biopsy showed extravascular epithelioid and gigantocellular non-caseating granulomas with lymphoid infiltrates. There was no sign of sarcoidosis or Crohn's disease. Treatment with hydroxychloroquine for three months, then with oral metronidazole, did not improve the symptoms. Minocycline (100 mg/d) was effective. CONCLUSION: Granulomatous cheilitis should be considered in children as well and differentiated from infectious, allergic or factitious dermatoses. Granulomatous cheilitis can be associated with Crohn's disease or sarcoidosis, and could precede these disorders from several months or years, thus requiring a long-term follow-up.

[Antiseptic treatment of the umbilical cord in newborns: survey and recommendations]. / Antisepsie du cordon ombilical du nouveau-né: enquête et recommandations.

AIM: To determine whether umbilical cord care of the neonate is in accordance with the guidelines of antiseptic treatment at this age of life. MATERIAL AND METHODS: A survey was conducted during the 3rd trimester of 1996 in 57 maternity units and departments of neonatalogy in the region of Provence-Alpes-Côte d'Azur (south of France). A questionnaire was sent to the head of each unit asking the modalities of disinfection of the umbilical cord. RESULTS: Fifty units answered the questionnaire. Six different groups of antiseptic products were used, corresponding to 17 distinct commercial preparations. The simultaneous association of several products (two or three) was done in 70% of cases. Eosin was the most frequently used (60%), in association with 25 units. Alcohol was used in 28 centers (56%). It was associated 22 times. Chlorhexidine was used in 16 units (32%), twice alone, and with another topic 14 times. The commercial association chlorhexidine-benzalkonium chloride (Biseptine) was reported seven times (six times in association with another topical treatment). Ektogan (a powder of Zn and Mg peroxide and Zn oxide) was used in ten centers, always in association. Hexamidine was used in four units, once in association. Silver nitrate, Milian solution, iodinated alcohol, and povidone iodine were respectively used once. CONCLUSION: This survey shows that a great variety of umbilical cord care modalities is used in this region, and that the recommendations for antiseptic treatment in young babies, are not always respected. According to these, eosin, ethanol, Ektogan and iodine should not be used for this purpose. Although chlorhexidine has been proven to be the most suitable disinfectant, it comes only in third place, used in association in 95% of the cases. Several studies in neonates have shown that it is well tolerated and efficient even if it delays cord separation. This study should lead to interdisciplinary consensual guidelines for umbilical cord care.

Demodicidosis in an immunodeficient child.

A 15-month-old girl developed acute lymphoblastic leukemia. Chemotherapy had induced a complete remission and she was continued on maintenance therapy. At 3 years of age, she developed an eruption consisting of excoriated papules and pustules on the face. Demodex folliculorum seemed to be the cause. Topical treatment with metronidazole applied twice a day over a period of 2 weeks resulted in partial improvement. The dermatosis finally cleared gradually with oral erythromycin therapy and one overnight application of 1% lindane cream per week for 2 successive weeks.

Visceral artery aneurysms in Von Recklinghausen's neurofibromatosis.

We report the case of a patient with Von Recklinghausen's neurofibromatosis in whom two visceral artery aneurysms were diagnosed: a 4 cm aneurysm originating from the common hepatic artery and a smaller aneurysm originating from the superior mesenteric artery. The hepatic artery aneurysm underwent successful embolization. Because of the patient's poor general condition, the superior mesenteric aneurysm was considered inoperable and has been kept under surveillance by ultrasonography. Arterial involvement in Von Recklinghausen's neurofibromatosis is a well-known but infrequent occurrence. Stenotic lesions predominate, with the renal arteries being the site of predilection. Aneurysmal defects are less common, and involvement of the visceral arteries is exceptional. Only three reports of superior mesenteric artery aneurysm in patients with Von Recklinghausen's neurofibromatosis were found in the literature, and hepatic artery aneurysm has never previously been described in this disease.

[Cutaneo-mucous manifestations of dengue]. / Manifestations cutanéo-muqueuses de la dengue.

OBJECTIVES: To describe muco-cutaneous manifestations of dengue fever, assessing their incidence and histopathological aspects. PATIENTS AND METHODS: During a dengue 2 epidemic, occurring in Guadeloupe in 1994, all patients admitted with a confirmed diagnostic of dengue fever were assessed for dermatological changes by 2 clinicians; 5 patients underwent skin biopsy with immuno-fluorescence staining. RESULTS: Among 39 adult inpatients (Sex ratio 1.1, medium age 41 years) none presented a severe form of the disease, whereas 18/39 (46 p. 100) had some muco-cutaneous changes, associating rash (13 cases (33 p. 100)), mucous membranes involvement (7 cases (18 p. 100)), or minor haemorrhages (6 cases (15 p. 100)). The rash appeared macular, discrete, itching, troncular with peripheral extension, rather than maculo-papular (morbiliform) as usually described. Apart from cases which minor haemorrhagic changes, significatively associated with marked thrombocytopenia (medium 37 x 10(9)/1), dengue cases either with or without muco-cutaneous changes had similar clinical (duration, severity) or biological (neutro-lympho-thrombocytopenia, transaminases) features, and evolution. Histological changes appeared non specific (minor lymphocytic dermal vasculitis, non contributive immuno-fluorescence). DISCUSSION: Clinical and histological features of the rash are unspecific and inconstant: they do not allow an easy and accurate diagnosis. Complete clinical, epidemiological (very recent travel in endemic areas) or biological data should be collected, and early virological or later serological confirmation is needed. As well as travel facilities are growing, the dengue area is extending: dengue fever should therefore be considered in every traveller with fever and rash.