Devices and methods for Integrated Bioprocessing have been developed for production of recombinant proteins with the yeast Pichia pastoris. In doing so cross flow filtration techniques for cell separation and product concentration are connected directly to high instrumented cultivation processes. These are equipped with on‐line measuring techniques for substrates and products, e.g., glycerol, methanol and pyruvate as well as recombinant proteins, e.g., the chemokines 1–8del MCP‐1 and vMIP‐II. Complex automation structures allow for process development at virtual plants which can be used as the basis for establishing and implementing fully automated real processes. Experiments for determination of reaction kinetics, optimization of productivity in high‐cell density cultures and Integrated Bioprocessing are outlined, along with detailed illustration of the realization of the methods at industrial pilot plant scale.

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The paediatrician and the child surgeon are not infrequently confronted by a form of congenital malformation of the angiomatous type, which is characterized by a diffuse, ill-defined, increase in the tissues and often involves an entire part of the body. The changes are usually confined to a n arm or a leg, but may occur a t multiple sites. The anatomical basis is a mixed haemolymphangioma with a preponderance in one or the other direction.The literature, including the large text-books of paediatrics, provides very varying and often incomplete descriptions of this pathological condition. Moreover, there are considerable discrepancies in the data regarding its pathogenesis and prognosis. Because we have had a number of cases at our hospital, we have been obliged to form a definite opinion with regard to these questions, as well as to various forms of therapy. An account of our experience is given in the foIlowing. NONNE in 1891 published a report of a family in which elephantiasis of thc legs occurred as a congenital-hereditary phenomenon. In the following year, MILROY described a family in which 20 out of 97 persons suffered from congenital oedenia of the legs and in an additional tm-o it developed a t a later age. A few years later, hfEIGE reported a further 8 cases. On the bash of these publications, and mainly in view of the symptomatology, it has becomc customary to regard Nonne-Milroy-hleige's disease or chronic hereditary oedenia as a separate clinical entity. I t is stated to be a hereditary-familial disease and to be consistently localized to the lower extremities (BRAHAM 8; HOWELLP; MEIGE; MILROY; SCHROEDER 8L HELWEG-LARSEN!. The data regarding the onset of the disease nevertheless vary; thus all MEIGE'S cases started during puberty. All the writers agree that, in this disease, the functional ability of the affected extremities is well maintained and that the cordilion is, on the whole, stationary. With regard to the pathogenesis, opinions are divergent and often based on hypotheses; conclusive histological studies are lacking. The most complete investigation appear6 to have been made by SCHROEDER 8L HELWEG-LARBEN, who described 11 cases; biopsy was performed in 4 of them. Fibrosis of the subcutaneous tissues then appeared to be the most salient feature, whereas the changes in the blood vessels and lymphatics were considerably less prominent.The isolated cases of non-familial congenital elephantiasis -ELTERICII 8; YOUNT and ALLEN el al. -differ from the aforementioned description. The clinical picture is fairly similar to that in Milrop's disease, but the histological basis of the malforma-

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