New J-3 flexible-leaflet polyurethane heart valve prosthesis with improved hydrodynamic performance.

The aim of this new three-leaflet valve development was to design a leaflet with minimum membrane stresses during performance. This is achieved by manufacturing the valve leaflets shaped almost flat in a medium opening position. Thus, the leaflets have two stable positions, one with maximum opening area and the other with favorable stress distribution in the closed position. The transition between the two end positions is achieved through a two-dimensional rolling motion without buckling and with minimum membrane stresses (bulge forces). The manufacturing technique is dip-coating in polyurethane. Hydrodynamic evaluation of the J-3 valve in steady and pulsatile flow showed minimum pressure drop compared to other commercially available valves. Laser-Doppler-anemometry studies indicated very low shear stresses in the flow field downstream of the valve. In durability tests prototypes have reached lifetimes of up to 17 years. In conclusion, the J-3 valve shows superior hydrodynamic performance thereby reducing potential thrombus formation. Minimization of stresses within the valve leaflets through design could reduce calcification.

Advances in design principle and fluid dynamics of a flexible polymeric heart valve.

The three leaflet J-3 valve is manufactured in a medium open position with almost flat leaflets, whereby the stent is expanded by a cone shaped mold. After manufacturing, the dipcoated leaflets have stable closed and open positions. The transition succeeds with very low membrane stresses. Due to this design, the J-3 polymer valve showed superior hydrodynamic performance compared with commercial valves. In durability tests, prototypes have reached lifetimes up to 17 years. While animal tests are encouraging, they also reveal needed manufacturing improvements.

[Correction of fatal genetic diseases using bone marrow transplantation. 2]. / Korrektur letal verlaufender genetischer Erkrankungen mit Hilfe der Knochenmarktransplantation. Teil 2.

Genetic diseases can be treated by transplantation of normal allogeneic bone marrow. Four patients with congenital disorders of their hematopoietic and/or lymphoid stem cells have been transplanted. One patient had a congenital aplastic anemia (Blackfan-Diamond), one had Gaucher's disease, one had congenital agranulocytosis Kostmann and one had chronic granulomatous disease. All patients received busulfan, cyclophosphamide and total nodal irradiation as preparatory regimen. Total nodal irradiation and cyclophosphamide were used as immunosuppressive agents. In all cases hematopoietic ablation and donor lymphoid and hematopoietic engraftment were achieved. The basic disorders of all transplanted children could be corrected completely. All children are alive and well.

[Correction of fatal genetic diseases using bone marrow transplantation. 1]. / Korrektur letal verlaufender genetischer Erkrankung mit Hilfe der Knochenmarktransplantation. Teil 1.

Bone marrow transplantation (BMT) was mainly used for the treatment of immunological, hematological and oncological diseases. Genetic diseases can also be treated by transplantation of normal histocompatible allogeneic bone marrow. This type of marrow transplantation is used for the treatment of inborn errors whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases is under investigation. Genetic disorders that can be cured include congenital immune deficiencies, infantile malignant osteopetrosis, thalassemia, infantile agranulocytosis, chronic granulomatous disease, lysosomal storage diseases and others. The use of autologous bone marrow after the insertion of a normal gene (gene therapy) in vitro circumvents the need for a histocompatible donor.

Status of allogeneic bone marrow transplantation in childhood in the GDR.

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.

Cryopreservation of marrow, purging and autologous bone marrow transplantation in childhood.

Since 1984 bone marrow from 42 children with acute lymphoblastic leukaemia, non Hodgkin's lymphoma and neuroblastoma was cryopreserved. In 5 cases (c-ALL, NHL and B type) the marrow was purged by using a cocktail of three monoclonal antibodies (VIL A1, VIB C5, VIB-E3). Up to now 13 children (ALL/10, neuroblastoma/3) were autografted (one of them after purging) after supralethal chemoradiotherapy. Except one child with early death all patients had engraftment: a level of 1.0.10(9)/l leukocytes was reached at days 10-33 (median, 19); platelet level over 60.10(9)/l at days 32-60 (median, 41). 2 children died on treatment related complications, one on infection after full haematological restitution, 2 patients alive with relapse, 8/13 alive in CCR and well.

[Cryopreservation of bone marrow for the autologous transplantation in children]. / Kryokonservierung von Knochenmark zur autologen Transplantation bei Kindern.

In preparing the autologous transplantation of children a method for cryoconservation of bone-marrow was developed by means of investigating the donor's bone-marrow. This method is adapted to our conditions, can easily be practised and is cell-preserving. Quantity and quality of the stored bone-marrow cells were evaluated concerning their proliferation capability by means of CFU-c assays. The highest recovery in CFU-c (78%) and cells (98%) was observed if isolated mononuclear cells with cryoprotective addition of 5% DMSO, 20% of human albumin, and 20% of serum were slowly frozen at a controllable rate, stored in liquid oxygen and thawed very quickly. According to the elaborated method the remission marrow was taken from 15 children affected with malignant diseases for autologous reinfusion. The data gained here confirm the experimental experiences.

[Lysis of leukemia cells with a monoclonal antibody-cocktail (e.g. VIP-pool) and human complement]. / Untersuchungen zur Lyse von Leukämiezellen mit einem monoklonalen Antikörpercocktail (sog. VIB-pool) und Humankomplement.

During the lysis of leukemic cells with a monoclonal antibody cocktail (the so-called VIB pool) and complement the attempt was made to replace rabbit serum as a complement source by human serum. For identifying the lysis of leukemic cells the complement-dependent in vitro cytotoxicity test was used and for excluding stem cell toxicity the CFU-c test according to PIKE and ROBINSON. In combination with the applied monoclonal antibody pool against B and c-ALL the human complement could be shown to be suitable to produce a lysis in the same manner as rabbit complement. Similarly to the pretested rabbit serum the treatment with the human complement had no impact on stem cell recovery. An optimal cytotoxic activity (95% against ALL blasts of patients, 100% against NALM) could be identified up to an antibody dilution of 1:32 with a volume percentage of 50% of human complement, an incubation temperature of at least 37 degrees C and an incubation time of 30 mins. With proved high reactivity against leukemic cells and lacking impairment of the haemopoietic power of the bone-marrow, this method can be recommended for "purging" protocol with the possibility of using human serum as a source of complement having advantages as far as clinical application is concerned.

[Use of human albumin as an additional cryoprotective agent in freeze preservation of hematopoietic stem cells]. / Verwendung von Humanalbumin als zusätzliches Kryoprotektivum bei der Tieftemperaturkonservierung hämatopoetischer Vorlüferzellen.

14 bone-marrow samples of healthy donors were cryopreserved with 5% of DMSO in combination with different volume percentages of 20% human albumin, with the protective impact of the respective freezing mixture on the proliferating capacity of early hemotopoietic precursor cells being determined by means of CFU-c-technique. A combination of 5% of DMSO with 20% of human albumin with an addition of 20% of autologous serum proved to be the most favourable freezing protection. CFU-c-recovery which was achieved in this way amounted to 78 +/- 7%. A protective impact of human albumin for CFU-c during incubation with the freezing medium at room temperature was statistically not significant. Thus, the method presented is suitable for cryopreservation of bone marrow for autologous transplantation. The advantages over the traditional procedure results from the slight degree of toxicity by reducing the DMSO percentage from the common 10% to 5% as well as from the fact that the thawed cell suspension may be directly infused with the substance for freezing protection, thus avoiding an additional loss of proliferative material. The procedure may be used especially for autologous transplantation in childhood.

[Model for a sociopsychiatric out-patient clinic? (author's transl)]. / Modell für eine sozialpsychiatrische Ambulanz? Uber die Arbeitsweise des Sozialpsychiatrischen Dienstes in Berlin

In the psychiatric social services of the Public Health Departments in Berlin (Charlottenburg, Spandau, Kreuzberg), data concerning the clients, the work of the coworkers and the quality of client care were collected. More than 80% of the clients of the psychiatric social service suffer from severe psychiatric disturbances: alcoholism, psychiatric geriatric illness and schizophrenia. This diagnosis range differs significantly from that of the physicians in a private practice. Competition, therefore, does not exist between the psychiatric social services and the psychiatrists in a private practice. --The coworkers of the social istuation (housing, profession, salary and social contacts) to be poor for every second (to third) client and unfavorable for the course of the disease. Psychiatric social care in the areas of medicine, nursing and welfare as well as the coordination of the care was evaluated as unsatisfactory for every second (to third) client. --Dor social workers and physicians, the percentage of direct patient-oriented activity was about 45%, the percentage of indirect patient-oriented activity was about 55%, about 40% of the work-time was used for administration. An improvement in the organization could free more work-time for meaningful activity. --The psychiatric social services fulfill an important function for out-patient care, particularly for the severly mentally disturbed. The existing gaps in client care cannot begin to be closed by just expanding the psychiatric social services in terms of personnel in the Public Health Department. Extensive structural changes must also be made in regard to psychiatric care.