Th.--Méd.--Saint-Étienne, 1980. N°: 13.

The purpose of the study was to determine the morphological capillary pattern of the mongoloids and compare this with another constitutionally retarded clincial group - the phenylketonurics- and the degree of deviation from the "normal" pattern. Photomicrographs were taken with capillary microscope and the capillaries were analysed into the ten basic morphological categories as set out by Gibson, Bosley and Griffiths (1956). It was concluded that the mongoloids and the phenylketonurics differed significantly in the amount of primitive immature configuration they displayed. The hypothesis of Powdermaker (1929) that structure is related to function, was found tenable through a capillaroscopic examination of scholastically retarded school children. / Medicine, Faculty of / Graduate

A mathematical model describing the transport and distribution of fluid and plasma proteins between the circulation, the interstitium, and the lymphatics, is formulated for the human. The formulation parallels that adopted by Bert et al.[5] in their model of microvascular exchange in the rat. The human microvascular exchange system is subdivided into two distinct compartments: the circulation and the interstitium. Both compartments are treated as homogeneous and well-mixed. Two alternative descriptions of transcapillary exchange are investigated: a homoporous "Starling Model" and a heteroporous "Plasma Leak Model". Parameters which characterize fluid and protein transport within the two models are determined by a comparison (quantified statistically) of the model predictions with selected experimental data. These data consist of interstitial fluid volumes and colloid osmotic pressures measured as a function of plasma colloid osmotic pressure for subjects suffering from hypoproteinemia. The relationship between this fitting data and the model transport parameters is investigated using a visual "graphical optimization technique" and additionally, in the case of the Starling Model, by use of a non-linear optimization technique. Both the Starling Model and the Plasma Leak Model provide good representations of the fitting data for several alternative sets of parameter values. The ranges of parameter values obtained generally agree well with those available in literature. The fully determined model is used to simulate the transient behaviour of the system when subjected to an intravenous infusion of albumin. All alternative "best-fit" parameter sets determined for both models produce simulations which compare reasonably well with the experimental infusion data of Koomans et al.[42]. The predictions of both models compare favourably not only with the available experimental data but also with the known behavioural characteristics of the human microvascular exchange system. However, no conclusions may be drawn regarding which of the alternative transcapillary transport mechanisms investigated provides the better description of human microvascular exchange, although it appears likely that diffusion of proteins plays a significant role in both. Final model selection and choice of fitting parameters await the availability of more and better microvascular exchange data for humans. Analysis of both the Starling Model and Plasma Leak Model indicates that the microvascular system is capable of regulating the interstitial fluid volume over a fairly wide range of transport parameter values. The important model-predicted passive regulatory mechanisms are tissue "protein washout", which reduces its colloid osmotic pressure,and a low tissue compliance which increases the hydrostatic pressure of the interstitium as it becomes hydrated. It would therefore seem that the human microvascular system can be regarded as a fairly "robust" system when considering its ability to regulate interstitial fluid volume (i.e., small changes in the values of transport parameters, such as the capillary wall permeability, have little effect on the conditions and operation of the system). / Applied Science, Faculty of / Chemical and Biological Engineering, Department of / Graduate

No description available.

Note:

Les RASopathies avec phénotype Noonan associent le syndrome de Noonan (SN), le syndrome cardio-facio-cutané (SCFC) et le syndrome de Costello (SC). Leurs manifestations dermatologiques restent peu étudiées.Objectifs Colliger les différentes manifestations dermatologiques des SN, SCFC et SC afin d’établir leur nature et leur prévalence, et définir d’éventuelles corrélations phénotype/génotype au sein de chacune de ces affections.Méthodes Les patients atteints d’un SN, SCFC et SC confirmé sur le plan moléculaire par la présence d’une mutation germinale pathogène étaient inclus dans une étude menée durant 5 ans dans les départements de Génétique, Dermatologie et Pédiatrie des CHU de Bordeaux, Marseille, Montpellier, Nancy, Nantes, Paris AP-HP (Hôpital Robert-Debré et Hôpital Necker-Enfants Malades), Rennes, Saint-Pierre (La Réunion) et Toulouse.Résultats Cent quatre-vingt-quatorze patients atteints de SN, SCFC et SC étaient inclus. Cent-vingt et un patients atteints de SN étaient inclus. La tendance aux hématomes était la manifestation la plus fréquente au cours du SN-PTPN11 (53.8%). Les ML et les tâches café-au-lait atypiques (≥3) étaient observés respectivement dans 94% et 80% des SNML liés à des mutations spécifiques de PTPN11. Des formes atypiques de SNML étaient associées au SN-RAF1 et SN-NRAS. En analyse univariée, les patients sans mutation PTPN11 présentaient (i) un risque de troubles de la kératinisation augmenté (P=0.001), dont la kératose pilaire (KP) (P=0.005), l’ulerythema ophryogenes (UO) (P=0.0001) et la kératodermie palmoplantaire (KPP) (P=0.06), et (ii) un risque augmenté d’alopécie du scalp (P=0.035) et des cils (P=0.06) par rapport aux patients sans mutation PTPN11.Quarante-cinq patients atteints de SCFC étaient inclus, parmi lesquels 77,8% avec mutation BRAF. Les anomalies pilaires étaient constantes, incluant une alopécie du scalp et des sourcils et des cheveux frisés ou bouclés respectivement dans 73% et 69% des cas. Une KP, un UO, une KPP et de multiples naevi (MN >50) étaient observés respectivement dans 82%, 44%, 27% et 29% des cas. L’alopécie des sourcils, l’association UO et KPP, la KP diffuse, et les MN constituaient des signes pertinents de différenciation du SCFC avec le SN et le SC. L’acitrétine orale permettait de traiter avec succès la KPP, tandis que le traitement de l’UO par sirolimus à 1% en topique échouait. Aucune corrélation phénotype-génotype n’était notée.Vingt-et-un patients atteints de SC étaient inclus, parmi lesquels 60% avec la mutation p.G12S-HRAS. Les anomalies pilaires étaient constantes, comprenant des cheveux frisés ou bouclés et une alopécie du scalp respectivement dans 70% and 60% des cas. Un acanthosis nigricans, des papillomes, une KPP, et une cutis laxa acrale étaient notés respectivement dans 65%, 65%, 55% et 80% des cas. Des papules linéaires à disposition pavimenteuse de la lèvre supérieure étaient présentes dans 55% des cas, tandis que l’alopécie des sourcils ou le lymphoedème n’étaient pas observés. Aucune corrélation phénotype-génotype n’était notée. Un patient avec SC atypique avec mutation c187_207dup21/p.Glu63_Asp69dup-HRAS présentait un phénotype cutané distinct associant des MN, un lymphoedème et des manifestations dermatologiques de SC, évoquant une nouvelle forme phénotypique de chevauchement entre un SC et un SN et/ou un SCFC.Conclusion La connaissance précise des manifestations dermatologiques des RASopathies et l’identification de thérapeutiques permet une optimisation de leur prise en charge. / Background Data on dermatological manifestations of RASopathies with Noonan phenotype including Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFCS) and Costello syndrome (CS) remain heterogeneous and based on little dermatological expertise.Objectives To describe the dermatological manifestations of NS, CFCS and CS compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11, BRAF and pG12S-HRAS mutations respectively for NS, CFCS and CS.Methods We performed a large, 5-year, prospective, multicentric, collaborative dermatological and genetic study.Results A total of 194 patients with NS, CFC and CS were included. One hundred and twenty-nine patients with NS were enrolled, including 65 with PTPN11-NS, 34 with PTPN11-NS with multiple lentigines (NSML), and 30 without PTPN11-NS. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53.8%. Multiple lentigines and café-au-lait macules (≥3) were present in, respectively, 94% and 80% of NSML linked to specific mutations of PTPN11. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P=0.001), including keratosis pilaris (P=0.005), ulerythema ophryogenes (P=0.0001) and palmar and/or plantar hyperkeratosis (P=0.06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P=0.035) and scarce or absent eyelashes (P=0.06, trend association) than those with PTPN11 mutations. Forty-five patients with CFCS were enrolled with mutations in BRAFin 77.8%. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair respectively in 73% and 69%. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmo-plantar hyperkeratosis (PPHK), and multiple melanocytic naevi (MMN; MN >50) were noted respectively in 82%, 44%, 27% and 29%. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP, and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical 1% sirolimus failed. No significant dermatological phenotype-genotype correlation was determined. Twenty-one patients with CS were enrolled with p.G12S mutation of HRAS identified respectively in 60%. Hair abnormalities were ubiquitous, including wavy or curly hair and scalp alopecia respectively in 70% and 60%. Acanthosis nigricans with pachydermatoglyphia, papillomas with periorificial location, PPHK, and acral cutis laxa were noted respectively in 65%, 65%, 55% and 80%. Cobblestone papillomatous linear papules of the upper lip was present in 55%, while scarcity of eyebrows and lymphedema were almost absent. No significant dermatological phenotype-genotype correlation was determined. One patient with CS with c187_207dup21/p.Glu63_Asp69dup mutation of HRAS had a new distinct cutaneous phenotype including MMN and severe lymphedema similar to NS and/or CFCS findings.Conclusions A thorough knowledge of RASopathies skin manifestations would help in making a positive diagnosis.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M. Soc. Sc.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 31-34).

Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2009. / Includes bibliographical references.