Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism.

The theory of bifurcating vascular systems predicts vessel diameters that are related to optimality criteria like minimization of pumping energy or of building material. However, mechanisms for producing the postulated optimality have not been described so far, and quantitative data on bifurcation diameters during development are scarce. We used an embryonic vascular bed that rapidly grows and adapts to changing hemodynamic conditions, the chicken chorioallantoic membrane (CAM), and correlated vascular cast and tissue section morphology with in vivo time-lapse video monitoring. The bifurcation exponent delta and associated parameters were quantitatively assessed in arterial and venous microvessels ranging in diameter from 30 to 100 microm. We observed emergence of optimality by means of intussusception, i.e., formation of transvascular tissue pillars. In addition to intussusceptive microvascular growth (IMG = expansion of capillary networks) and intussusceptive arborization (IAR = formation of feeding vessels from capillaries) the observed intussusception at bifurcations represents a third variant of nonsprouting angiogenesis. We call it intussusceptive branching remodeling (IBR). IBR occurred in vessels of considerable diameter by means of two alternative mechanisms: either through pillars arising close to a bifurcation, which increased in girth until they merged with the connective tissue in the bifurcation angle; or through pillars arising at some distance from the bifurcation point, which then expanded by formation of ingrowing tissue folds until they became connected to the tissue of the bifurcation angle. Morphologic evidence suggests that IBR is a wide-spread phenomenon, taking place also in lung, intestinal, kidney, eye, etc., vasculature. Irrespective of the mode followed, IBR led to a branching pattern close to the predicted optimum, delta = 3.0. Significant differences were observed between delta at arterial bifurcations (2.70 to 2.90) and delta at venous bifurcations (2.93 to 3.75). IBR, by means of eccentric pillar formation and fusion, was also involved in vascular pruning. Experimental changes in CAM hemodynamics (by locally increasing blood flow) induced onset of IBR within less than 1 hr. Our study provides morphologic and quantitative evidence that a similar cellular machinery is used for all three variants of vascular intussusception, IMG, IAR, and IBR. It thus provides a mechanism of efficiently generating complex blood transport systems from limited genetic information. Differential quantitative outcome of IBR in arteries and veins, and the experimental induction of IBR strongly suggest that hemodynamic factors can instruct embryonic vascular remodeling toward optimality.     

Disturbed myelinogenesis and recovery in hyperphenylalaninemia in rats: An immunohistochemical study

Chronic hyperphenylalaninemia (HPA) in rats has been used as an experimental model of the human inborn error of metabolism phenylketonuria (PKU). Impaired brain development in PKU and HPA is reflected in reduced myelin formation. We have used immunohistochemistry, with antibodies to cell-specific antigenic markers, to investigate the cellular basis of the hypomyelination in the corpus callosum and cerebral cortex of rats made hyperphenylalaninemic from Postnatal Days 3-17. The rats were then allowed to recover until Day 59. No effects were seen on the number and differentiation pattern of ganglioside GD3-expressing glial progenitors. Myelin basic protein and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP) immunostaining demonstrated a reduction in myelin formation in the corpus callosum and subcortical white matter at 12 and 17 days postnatal. However, numbers of CNP+ oligodendrocytes appeared normal throughout development. No reactive astrogliosis was seen at any stage. The intensity of axonal neurofilament immunostaining was reduced in the corpus callosum at 17 days. In layers II and III of the cortical gray matter there was an increase in the cell packing density and a concomitant decrease in cell body size. Myelination in the corpus callosum was rapid during the recovery period with no difference noted at Day 59. Axonal neurofilament staining also returned to normal in the corpus callosum. However, recovery became increasingly incomplete away from the corpus callosum into the cortical gray matter. Our data suggest a primary effect of HPA on axonal maturation with hypomyelination consequential upon this.     

Pregnancy following induced abortion: maternal morbidity, congenital abnormalities and neonatal death. Royal College of General Practitioners/Royal College of Obstetricians and Gynaecologists Joint Study

In a prospective cohort study of the long-term sequelae of induced abortion, a comparison is made between a group of 6418 women who had an induced abortion (cases) and a control group of 8059 women recruited with an unplanned pregnancy which was not terminated with an induced abortion (controls). The present paper reports on 729 cases and 1754 controls who had a post-recruitment pregnancy. In general, prior induced abortion had no material effect on the rate of pregnancy-related morbidity, nor on the rate of congenital abnormalities and neonatal death in the offspring. There was, however, a significant difference in two specific conditions. In the post-index pregnancy in the cases there was an increased relative risk (RR 2.26) of the occurrence of urinary tract infection and a decreased risk (RR 0.25) of pregnancy-related anaemia.     

Open fractures of the elbow joint

Both in open and in closed elbow fractures, anatomical joint reconstruction and rigid internal fixation, which permit early initiation of motion, are essential for good joint function. However, in open distal intraarticular humerus fractures this is more difficult to achieve, owing to the high rate of comminuted types C 2 and C 3 fractures. In addition, the extensive soft tissue lesions often mean that physiotherapy cannot be started until later than would otherwise be desirable. This retrospective study shows that the functional results in 60 patients operated on for correction of open distal intraarticular humerus fractures were worse (1/3 "excellent/good", 2/3 "moderate/poor") than those in patients treated for closed fractures. Complications included superficial infection in 7 patients, osteitis in 11, late instability in 10, fatigue failure of the implants in 5, and non-union in 10 patients.     

Load stability in relation to the osteosynthesis method, course and complications in open lower-leg fractures with severe soft tissue lesions

The external fixator ("fixateur externe") is today's method of choice in the treatment of lower leg fractures with severe damage to the soft parts. The various application techniques and angles of application of this device entail varying stability and are characterized by certain advantages and drawbacks. Basing on detailed biomechanical studies and experience with patients, the authors prefer the rectangular mode of application using Schanz screws. If the type of fracture allows, a combination of minimal osteosynthesis and external tensor is used; this can significantly enhance the stability. In 42 patients of a total of 56 during 1978-1980 with second-grade and third-grade open fractures of lower leg, combination with minimal osteosynthesis was effected (traction screw). Of 44 patients followed up, 19 achieved stability to load within an average period of 19.8 weeks. If there is no osseous bridging 10-12 weeks after initial treatment, additional measures such as spongiosaplasty and changeover to stable inner fixation with plates become necessary. Following plate osteosynthesis with additional spongiosaplasty, full load was permissible on the average 14 weeks after this procedure in 23 patients. The course was more complicated in the case of the 2 remaining patients; it took up to 45 weeks until full load became permissible.     

Die Veränderungen der physikalischen Eigenschaften von Polyacetalharz (Hostaform,C®), Polyester (Hostadur®), Polyäthylen (Hostalen®) und Teflon (Hostaflon®) nach tierischer Implantation und mehrfachem Autoklavieren

Zusammenfassung Nach 4- und 12wöchiger Implantation in der Rückenmuskulatur von 6 Monate alten gleichgewichtigen männlichen Kaninchen sowie nach ein- bis viermaligem Autoklavieren erfolgte die Untersuchung von standardisierten Probekörpern aus Polyacetalharz (Polyoxymethylen-Copolymer), Polyester (Polyäthylenterephthalat), Polyäthylen und Teflon (Polytetrafluoräthylen) im Rahmen eines Zugversuches. Dabei zeigte es sich, daß Polyester durch Implantation und Autoklavieren eine starke Verminderung der viscoelastischen Eigenschaften erfährt. Während Polyäthylen und Teflon nach beiden Behandlungen im wesentlichen unveränderte Eigenschaften aufweisen, läßt sich bei Polyacetalharz nach 12wöchiger Implantation und viermaligem Autoklavieren nur eine leichte Verminderung der viscoelastischen Eigenschaften im Sinne einer Versprödung von 10 bis 15% nachweisen.Die histologisch-qualitative Beurteilung des umliegenden Gewebes ergibt eine überragende Gewebsverträglichkeit von Polyäthylen, während bei den drei übrigen Kunststoffen Polyacetalharz, Polyester und Teflon eine vergleichbare Fremdkörperreaktion nach 4 Wochen erkennbar ist, die nach 12 Wochen jedoch deutlich abgenommen hat.

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The change of physical properties of plastics (polyoxymethylenecopolymer, polyethyleneterephthalate, polyethylene, polytetrafluorethylene) after animal implantation and autoclavation

Summary The change of physical properties of plastics (polyoxymethylene-copolymer, polyethyleneterephthalate, polyethylene, polytetrafluorethylene) and the bio-compatibility of these materials were examined by implantation in the backmuscle of 6-month-old male rabbits for 4 and 12 weeks and after autoclavation.We have found out, that after implantation and autoclavation polyethyleneterephthalate demonstrates a strong diminution of the visco-elastic qualities. Polyethylene and polytetrafluorethylene were not changed by these treatments. After an implantation of 12 weeks and an autoclavation of four times the visco-elastic properties of polyoxymethylene-copolymer were only slightly diminished by 10 to 15%.The histological investigation of the surrounding tissue demonstrated a very good bio-compatibility of polyethylene. After an implantation of 4 weeks polyoxymethylene-copolymer, polyethyleneterephthalate and polytetrafluorethylene produced a comparable foreign body reaction, which, however, was evidently diminished after an implantation of 12 weeks.

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Mit Unterstützung der DFG (Schwerpunkt Biopolymere und Biomechanik von Bindegewebssystemen).

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Für Beratung und Unterstützung danken wir Herrn Prof. Dr. H. Ueberberg, Biberach, Abteilung für Experimentelle Pathologie der Firma Dr. K. Thomae.     

Near-fatal cerebellar swelling caused by acute multifocal cerebellar necrosis.

We report a case of acute near-fatal cerebellar swelling, which was accompanied by multifocal cerebellar necrosis. Acute, near-fatal cerebellar swelling is a rare problem thought to be of parainfectious aetiology. Initiation by multifocal cerebellar necrosis has not been reported so far with this disorder.     

Extradural endodermal cyst of posterior fossa: case report, review of the literature, and embryogenesis

OBJECTIVE AND IMPORTANCE: Posterior fossa endodermal cysts are rare. They are located in the midline, in ventral or ventrolateral locations, or intrinsic to the neural axis. Accordingly, various theories of embryogenesis have been proposed. We report the first case of an extradural, dorsolaterally situated endodermal cyst. CLINICAL PRESENTATION: An adult male patient presented with a short history of headache and cerebellar ataxia. Neuroimaging revealed an extra-axial cystic posterior fossa mass. INTERVENTION: An entirely extradural cyst was found and was totally excised. Immunohistochemistry confirmed the diagnosis of endodermal cyst. CONCLUSION: The extradural, dorsal location of the endodermal cyst suggests gaps at the cranial end of the notochord causing ectodermal-endodermal adhesions during early gastrulation and the persistence of endodermal remnants in the dorsal mesenchyme of the blastemal cranium. The literature is reviewed, and proposed theories of embryogenesis are discussed.     

Implications of Liver Cirrhosis in Pregnancy

Summary: We present the case of a pregnant woman with alcohol-induced liver cirrhosis and a discussion of the clinically relevant issues of cirrhosis in pregnancy.