The systemic and SmD183-119-autoantigen-specific cytokine memory of Th cells in SLE patients.

OBJECTIVES: The aim of the study was to analyse the cytokine memory of T-cells derived from systemic lupus erythematosus (SLE) patients and healthy donors enriched for autoantigen-specific T-cells by in vitro stimulation with SmD1(83-119), a common autoantigen in SLE. METHODS: Autoreactive CD3+ T-cells derived from 37 SLE patients and 14 healthy donors were enriched by repetitive ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with SmD1(83-119). For control, PBMCs were stimulated only with interleukin-2 (IL-2). After two rounds of antigenic stimulation, cultures were stimulated with PMA/ionomycin to probe the cytokine memory by intracellular cytokine staining. Frequencies of cytokine-expressing T-cells were analysed and, in SLE patients, compared with disease activities and autoantibody levels. RESULTS: Comparing the cytokine memory in the cultures, SLE patients displayed higher frequencies of tumour necrosis factor-alpha (TNF-alpha)+ T-cells than healthy donors and the frequencies correlated with disease activity. Frequencies of SmD1(83-119)-specific TNF-alpha+ T-cells and of memory T-cells expressing interferon-gamma (IFN-gamma) correlated with serum anti-dsDNA antibody levels. The frequencies of IL-10 expressing SmD1(83-119)-specific T-cells were lower among PBMCs of SLE patients. Relatively higher frequencies of IL-10+ T-cells in SLE patients correlated with low disease activities, and low anti-dsDNA and anti-SmD1(83-119) antibody concentrations in culture supernatants. CONCLUSIONS: The memory of autoreactive SmD1(83-119)-specific and unspecific stimulated peripheral Th cells for re-expression of cytokines is shifted towards more cells expressing TNF-alpha and less IL-10+ cells, when compared SLE patients with normal donors. This shift towards proinflammatory memory effector Th cells correlates with disease severity and humoral autoimmunity.

T cell cytokine imbalance towards production of IFN-gamma and IL-10 in NZB/W F1 lupus-prone mice is associated with autoantibody levels and nephritis.

OBJECTIVE: The role of T cell-derived cytokine production in lupus is poorly understood. We analysed the cytokine production of CD4(+) T cells in the NZB/W F1 mouse strain, the mouse model probably most closely resembling human systemic lupus erythematosus (SLE), and assessed whether a possible shift in the cytokines expressed is associated with age or disease activity. METHODS: We used intracellular cytokine staining and flow cytometry to determine the cytokine expression of splenic CD4(+) T cells for interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and IL-10. NZB/W F1 mice at different ages spanning 5 to 36 weeks were analysed, healthy Balb/cxNZW F1 (CWF1) mice were used as controls. Serum anti-double-stranded DNA (anti-dsDNA) antibody levels were determined by enzyme-linked immunosorbent assay (ELISA), and proteinuria and plasma creatinine were estimated using commercial test kits. RESULTS: The cytokine profile of CD4(+) T cells was shifted towards T-helper 1 (Th1) cells and the frequencies of Th cells expressing IFN-gamma(+) correlated with age, anti-dsDNA-immunoglobulin G (IgG) titre and proteinuria. An increased percentage of IL-10 producers correlated positively with anti-dsDNA-IgG and proteinuria, and a small gain in IL-4 producers correlated with plasma creatinine. Neither the percentage of IL-10 producers nor IL-4 producers showed a significant correlation with age. There was no significant change observed in the frequency of TNF-alpha T cells. The IFN-gamma/IL-4 ratio demonstrated an increasing shift towards a Th1-type response during disease development that was not present in healthy mouse strains. CONCLUSION: The association between the frequencies of T cells expressing IFN-gamma and IL-10 and clinical findings suggests a key role for these cells in the pathogenesis of lupus.

Staff escorting centralized cardiotocographic surveillance (level 3: cardiotocographic surveillance).

As cardiotocograms may exceed borderline values unnoticed if the parturient/staff ratio exceeds 1/1 the distributions of deliveries and simultaneous occupancies of delivery beds over 11 years are analyzed. Variable influences, for example the management of labor, are outlined. The first level 3: staff escorting of centralized cardiotocographic surveillance in a family oriented obstetrical set up and its computerbased alert-system are described. Requirements for humane and safe parturition are formulated.

[Spontaneous labor in the 38th week of pregnancy under intermittent hemodialysis treatment of the mother. Alloimmune thrombocytopenia of the newborn infant]. / Spontangeburt in der 38. SSW unter intermittierender Hämodialysebehandlung der Mutter. Alloimmunthrombozytopenie des Neugeborenen.

Uncomplicated pregnancies and spontaneous deliveries of term infants are rare if mothers are treated by haemodialysis because of terminal renal insufficiency. Pregnancies under these circumstances mostly end in abortion or stillbirth; live births are mostly delivered by Caesarean section. Independent of the mother's basic disease the infant of this case was born at 38 weeks spontaneously with a neonatal alloimmune thrombocytopenia, which is analogous to Rh-haemolytic disease of the newborn.

Primary osteogenic sarcoma of the breast.

A rapidly growing tumor in the left breast of a 38-year-old woman was mammographically suggested to be a fibroadenoma because of its sharply circumscribed and quite homogeneous shadow, with coarse calcifications. Fine needle aspiration biopsy showed an unusual cytologic picture, with polymorphous and multinucleated giant tumor cells and scattered plaques of osteoid. After excision followed by mastectomy, the tumor was histologically diagnosed as an osteogenic sarcoma. Radiologically, there was no evidence of another tumor localization. The cytologic findings of this rare tumor, never previously reported, are presented.

[Cytologic diagnosis of malignant melanomas of the female genital tract (author's transl)]. / Zytologische Diagnostik maligner Melanome des weiblichen Genitale.

From 1969-1978 3 primary malignant melanomas of the vulva and 2 metastatic melanomas of the cervix were detected among 148,000 gynaecological cytosmears. Two melanomas of the vulva were diagnosed primarily by cytology because melanin was found. In the metastatic melanomas the primary site was known in one case. In the other case the primary malignancy of the skin was detected when the cytosmear from the cervix was diagnostic of matastatic melanoma. The literature and the personal experience on the possibilities of the cytological diagnosis of melanomas are discussed.

[Acute intrauterine hypoxia]. / Akute intrauterine hypoxie.

It is most commonly caused by cord compression and decreased utero-placental perfusion. Among all diagnostic procedures cardiotocography is most effective. The dignity of the different pathologic heart rate patterns varies. By technical and organisational means such as central control panels and automatic alert systems registered data are continuously evaluated even if the staff is limited. A number of therapeutical procedures may be chosen instead of rapid delivery. To a certain degree acute intrauterine asphyxia can be prevented.

[Desire for children and the practice of family planning]. / Kinderwunsch und Praxis der Familienplanung

Of 1647 women in confinement (mean age 26years) and 185 students nurses (mean age 18 years), the majority wanted two children. 8% of the women in confinement and 2% of the student nurses had received no previous family planning information, whereas 38% of the women in confinement and 81% of the student nurses had practiced contraceptive methods with a Pearl-index of 3 or less (oral contraceptives, basal-temperature-method). 31% of the women in confinement had already had unplanned pregnancies (mean: 1.4 pregnancy per woman). The last pregnancy was not planned in 27% and in these 4 out of 5 pregnancies were caused by incorrect application of the contraceptive method. Faulty practices and unsatisfactory results, in spite of the availability of secure contraceptive methods, emphasize the necessity of intensifying family planning. Because programmes including personal counsel have yielded better results, these should be favoured and include a clinical post partum programme. The latter was considered necessary by 95% of the women attending such a programme in our hospital.

PIP: Of 1647 women in the puerperium (mean age 26 years) and 185 student nurses (mean age 18 years), the majority wanted 2 children. 8% of the women in puerperium and 2% of the student nurses had received no previous family planning information, whereas 38% of the postpartal women and 81% of the student nurses had practiced contraceptive methods with a Pearl-index of 3 or less (oral contraceptives, basal temperature method). 31% of the maternity patients had already had unplanned pregnancies (mean: 1.4 pregnancy per woman). The last pregnancy was not planned in 27% and in these 4 out of 5 pregnancies were due to incorrect application of the contraceptive method. Faulty practices and unsatisfactory results, in spite of the availability of secure contraceptive methods, emphasize the necessity of intensifying family planning. Because programs, including personal counseling have yielded better results, these should be favored and include a clinical postpartum proram. The latter was considered necessary by 95% of the women attending such a program in our hospital.