Flexible fluidic microchips based on thermoformed and locally modified thin polymer films.

This paper presents a fundamentally new approach for the manufacturing and the possible applications of lab on a chip devices, mainly in the form of disposable fluidic microchips for life sciences applications. The new technology approach is based on a novel microscale thermoforming of thin polymer films as core process. The flexibility not only of the semi-finished but partly also of the finished products in the form of film chips could enable future reel to reel processes in production but also in application. The central so-called 'microthermoforming' process can be surrounded by pairs of associated pre- and postprocesses for micro- and nanopatterned surface and bulk modification or functionalisation of the formed films. This new approach of microscale thermoforming of thin polymer film substrates overlaid with a split local modification of the films is called 'SMART', which stands for 'substrate modification and replication by thermoforming'. In the process, still on the unformed, plane film, the material modifications of the preprocess define the locations where later, then on the spatially formed film, the postprocess generates the final local modifications. So, one can obtain highly resolved modification patterns also on hardly accessible side walls and even behind undercuts. As a first application of the new technology, we present a flexible chip-sized scaffold for three dimensional cell cultivation in the form of a microcontainer array. The spatially warped container walls have been provided with micropores, cell adhesion micropatterns and thin film microelectrodes.

3D tissue culture substrates produced by microthermoforming of pre-processed polymer films.

We describe a new technology based on thermoforming as a microfabrication process. It significantly enhances the tailoring of polymers for three dimensional tissue engineering purposes since for the first time highly resolved surface and bulk modifications prior to a microstructuring process can be realised. In contrast to typical micro moulding techniques, the melting phase is avoided and thus allows the forming of pre-processed polymer films. The polymer is formed in a thermoelastic state without loss of material coherence. Therefore, previously generated modifications can be preserved. To prove the feasibility of our newly developed technique, so called SMART = Substrate Modification And Replication by Thermoforming, polymer films treated by various polymer modification methods, like UV-based patterned films, and films modified by the bombardment with energetic heavy ions, were post-processed by microthermoforming. The preservation of locally applied specific surface and bulk features was demonstrated e.g. by the selective adhesion of cells to patterned microcavity walls.

Effect of stress on track formation in amorphous iron boron alloy: ion tracks as elastic inclusions

In a recently developed model of ion beam induced plastic deformation of amorphous solids, ion tracks are described as cylindrical thermoelastic inclusions formed upon local heating and shear stress relaxation along the ion trajectories. According to this model, track formation can be influenced or even suppressed by an applied stress. This model prediction is tested by studying the influence of stress on the etching of tracks of 2.4 GeV Pb in foil samples of the glassy metal Fe 81B 13.5Si 3.5C (2), where a compressive in-plane stress was built up in limited zones by preirradiation with a high fluence of 200 MeV Xe ions. The variation of the size of the observed etch pits with the local stress is found to be consistent with the model predictions, thus confirming the thermal spike origin of the tracks.

Cutaneous involvement in prelymphomatous angioimmunoblastic lymphadenopathy.

We describe prelymphomatous angioimmunoblastic lymphadenopathy with cutaneous involvement in a 73-year-old female patient. A maculopapular skin eruption was the first sign of the disease. Skin histology showed extensive perivascular and periadnexal mixed lymphoid infiltrates including centroblasts and immunoblasts with a high proliferative index and with focal erythrocyte extravasation. Lymph node histology confirmed the diagnosis, showing nearly complete effacement of the follicular architecture, a mixed lymphoid infiltrate, and numberous high endothelial venules in an expanded T-cell zone. Immunohistochemistry, however, demonstrated preservation of at least some follicular structures. T-cell receptor gene rearrangement analysis revealed oligoclonal patterns in both lymph node and skin specimens. In contrast, immunoglobulin heavy-chain gene rearrangement analysis revealed a polyclonal pattern. Accordingly, the disease was classified as a prelymphomatous stage of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) with specific involvement of both lymph node and skin. The patient was treated with high-dose corticosteroids, and long-lasting remission was induced. In contrast to our case, most reported cases of AILD show a monoclonal T-cell pattern indicating AILD-type lymphoma. Therefore we discuss the concept of prelymphomatous AILD developing into AILD-type lymphoma. Persistence of some antigenic stimulus may induce the proliferation of a monoclonal population of lymphoid cells from a polyclonal background in a multistep fashion. Proper treatment of AILD at an early, prelymphomatous stage may protract or inhibit development of full-blown, fatal AILD-type lymphoma.

Symmetric lipomatoses in female patients.

BACKGROUND: Symmetric lipomatoses are characterized by marked symmetric deposition of diffusely distributed fatty tissue. Though relatively common disorders, they are rather rarely reported in the literature, possibly being misdiagnosed as general obesity. While the differential diagnosis of symmetric lipomatosis versus general obesity may not appear difficult in males, it is obviously problematic in females. OBSERVATIONS: We describe the findings in 6 representative female patients with symmetric lipomatoses: 3 with benign (multiple) symmetric lipomatosis and 3 with female zonal obesity. The former disorder was characterized by massive, firm, symmetric fat deposition predominantly around the neck and shoulder girdle and was clearly associated with alcohol abuse and/or liver disease. There were no malignant tumors of the upper airways. In the latter case, fatty tissue had accumulated mainly at the buttocks and thighs but characteristically spared the feet and hands. Tenderness was a common symptom. This disorder showed familial predisposition. Histology in both cases revealed normal fatty tissue which was neither encapsulated nor septally divided. CONCLUSIONS: We suggest that the term 'symmetric lipomatoses' refers to two separate disorders, benign (multiple) symmetric lipomatosis and female zonal obesity.

Fulminant metastatic calcinosis with cutaneous necrosis in a child with end-stage renal disease and tertiary hyperparathyroidism.

Metastatic calcinosis is a common feature of chronic renal failure. Its first manifestations are bone demineralization and non-visceral and/or visceral calcification with mostly mural deposits in arteries and arterioles. It is initially characterized by hyperphosphataemia followed by secondary or tertiary hyperparathyroidism. Cutaneous involvement is a rare complication. Histologically, the lesions show vascular calcification with ischaemic skin necrosis. Extreme cases may produce calcinosis cutis (calciphylaxis), i.e. disseminated calcification of the subcutaneous tissue and dermis in the form of hard painful cutaneous nodules and plaques with subsequent ulceration. Metastatic calcinosis is a disease affecting adults, while the dystrophic or idiopathic type can develop in children. We present the case of a 6-year-old boy with end-stage renal disease, attributed to congenital renal hypoplasia, and accompanied by secondary hyperparathyroidism. He developed fulminant tertiary hyperparathyroidism and metastatic calcinosis of the lungs, as well as cutaneous necrosis of the buttocks and legs, subsequent to calcification of arteries and arterioles. A maternal renal transplant failed to function. The serum parathormone, calcium and phosphate levels could not be controlled by maintenance dialysis, phosphate binders and calcitriol. Total parathyroidectomy without autotransplantation of parathyroid tissue rapidly returned the serum parathormone, calcium and phosphate levels to normal. In addition, topical treatment using merbromine solution and hydrocolloid dressings, healed the ulcers with significant scar formation, within 2.5 months after parathyroidectomy. A renewed increase of the calcium x phosphate product, 2 months after parathyroidectomy, was attributed to mobilization of calcium compounds from the viscera, as confirmed by a chest X-ray.

[Rare variants of cutaneous T-cell lymphomas]. / Seltene Varianten kutaner T-Zell-Lymphome.

Besides the classical forms of cutaneous T-cell lymphoma (C-CTCL), such as mycosis fungoides and Sézary's syndrome, unique variants may be encountered. The classification of these rare cutaneous T cell lymphomas is problematic and controversial. Newer classifications of lymphoma in general, such as the Revised European-American Lymphoma (REAL) Classification, emphasize well-established clinico-pathological entities. It seems appropriate to attempt to bring greater clarity to the classification of cutaneous T-cell lymphomas using the same principles. In this review, we list and characterize the rare variants of cutaneous T-cell lymphoma, such as (1) clinical, histological and immunological variants of mycosis fungoides; (2) progressive cutaneous T-cell lymphoma (P-CTCL) including transformed classical cutaneous T-cell lymphoma (TC-CTCL) and primary progressive cutaneous T-cell lymphoma (PP-CTCL); (3) angiocentric and angioimmunoblastic cutaneous T-cell lymphomas; (4) large cell anaplastic, CD30+ cutaneous T-cell lymphoma; (5) HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL); (6) cutaneous manifestations of primary extracutaneous T-cell neoplasias; (7) unclassifiable cutaneous T-cell lymphoma.

[Generalized molluscum contagiosum in an African child with AIDS]. / Mollusca contagiosa generalisata bei einem afrikanischen Kind mit Aids.

A 12-year-old girl from Zaire with AIDS (CDC: P2 D1) presented with a generalized molluscum contagiosum infection. She had suffered from systemic cryptococcosis and from cryptosporidiosis several months before admission. While molluscum contagiousum infection is usually a self-limiting disease in immunocompetent persons, a fulminant appearance and persistence of giant mollusca occurs with advanced immunodeficiency. Histological and immunohistological examinations showed a severe diminution of Langerhans and T cell populations that might enhance the dissemination of the infection. Molluscum-like lesions of cryptococci have been described, and cutaneous cryptococcosis is the main condition to be considered in the differential diagnosis. Further differential diagnoses should include American and African histoplasmosis, and the cutaneous manifestations of mycobacterial infections, of toxoplasmosis and of Pneumocystis carinii infection.

[Large cell anaplastic Ki-1 positive lymphoma of the skin. 5 personal cases and review of the literature]. / Das grosszellig-anaplastische Ki-1-positive Lymphom der Haut. Fünf eigene Beobachtungen und Literaturübersicht.

Primary cutaneous large cell anaplastic non-Hodgkin lymphomas positive for Ki-1-antigen are rarely described. There are 100 published cases worldwide. Typically large cell anaplastic lymphomas have an inflammatory appearance, which often leads to false diagnosis and unsuccessful treatment with antibiotics. Histological examination reveals a highly malignant non-Hodgkin lymphoma. The tumour is composed of large pleomorphic lymphoid cells composed of T-cells in 80% of the cases and of B-cells in 10%. The immunological phenotype in the remaining 10% remains unclear. Crucial for the diagnosis is the expression of CD30 antigen in > 70% of the tumour cells. This article presents 5 cases of cutaneous Ki-1-positive lymphoma seen in our Berlin department during the last 10 years. In 4 patients the diagnosis was established in clinical stage I of cutaneous lymphoma without further manifestation; 1 patient had lymph node involvement and was in stage II. Total excision of the primary tumour in stage I with adjuvant polychemotherapy in stages II-IV led to complete remission in all cases. Long-term remissions were seen in case 1 (2 years) and in case 5 (1 year), whilst 2 patients showed local relapse, and 1 patient showed generalized lymphogenic and hematogenic metastasis. After repeated surgical removal or irradiation of the tumour and adjuvant polychemotherapy, further complete remission was achieved in 2 patients (up to now lasting 1 and 4 years). another patient has been in partial remission for the last 2 years. Our observations underline the high relapse rate of large cell anaplastic lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative experimental studies of mechanical and holmium laser synovectomy]. / Vergleichende experimentelle Untersuchungen zur mechanischen und Holmiumlaser-Synovektomie.

The goal of this study was to evaluate tissue reactions in rabbit knees following laser synovectomy using a holmium:YAG laser (wavelength: 2.1 microns) and to compare these results with those found after conventional mechanical abrasion treatment. Chronic arthritis was immunologically induced in one knee joint each of 48 rabbits. Twelve served as controls, 12 were sham-operated, 12 were exposed to laser radiation, and 12 others were treated according to conventional methods. In the laser group, a pulse length of 1 ms at a repetition rate of 3 Hz resulted in a pulse energy of 600 mJ. After periods of 1 day, 1 week and 1 and 3 months, respectively, three animals from each group were sacrificed and the synovialis was examined macroscopically and histologically using light and electron microscopy. Edema, acute inflammation, and coagulation necrosis occurred immediately following laser therapy. After 1 week, the synovial layer showed slight fibrosis, which was comparable to that found in the controls. One month later the surface appeared to be smooth. The mechanical abrasion caused hemorrhage and necrosis. Fibrosis was pronounced in all capsular layers, and after 3 months the surface appeared coarse and villous in this group. Based on these preliminary findings, holmium-laser synovectomy may offer an alternative to existing therapeutic techniques in the treatment of rheumatoid arthritis. The arthroscopic approach could prevent additional capsular fibrosis associated with mechanical irritation.

Holmium-laser synovectomy of immune synovitis in rabbits.

Holmium-laser synovectomy was carried out to remove allergically inflamed synovial membranes in rabbit knee joints. The healing process was then investigated at different periods. Left knee joints of 12 rabbits were exposed to Ho:YAG-laser radiation at a wavelength of 2.1 microns, pulse energy of 600 mJ, pulse length of 1 ms, and repetition rate of 3 Hz. Twelve others were treated conventionally and 12 served as controls. After 1 day, 1 week, and 1 and 3 months, respectively, 3 animals from each group were sacrificed and the synovialis grossly and microscopically examined. Coagulation necrosis, inflammation, and edema resulted following laser therapy. After 1 week, the synovial layer consisted of a scarlike formation of fibers and within 1 month, its surface appeared smooth. The mechanical abrasion caused hemorrhage and necrosis. Fibrosis developed in the capsular layers, and after 3 months, the surface appeared coarse and villous. Based on these preliminary findings, holmium-laser synovectomy may offer an alternative method to existing therapeutic techniques.

[Laparoscopic laser cholecystectomy]. / Laparoskopische Lasercholezystektomie.

In an ex vivo- and an animal study a Holmium-YAG laser, a Nd:YAG laser and a CO2 laser were examined. For laparoscopic cholecystectomy the pulsed Holmium:YAG laser proved to be the best instrument. Dissecting and haemostatic effects were connected when working with a power of 4 watts. Dissected area per minute was 112 mm2, gallbladder dissection (15 cm2) can be performed in 13 min. In the animal study the cholecystectomy lasted 30 min on average when the Holmium:YAG laser was used. Bleeding was not observed, development of smoke was tolerable.