[Current aspects of oncological rehabilitation]. / Onkologische Rehabilitation. So finden Krebspatienten in den Alltag zurück.

On completion of acute medical treatment oncological rehabilitation serves the purpose of re-integrating the patient into the everyday situation, family and working life, while at the same time improving his/her quality of life. The aims of outpatient or inpatient rehabilitation are based on an individual analysis of both physical and psychosocial problems and are implemented within the framework of an interdisciplinary therapeutic program. Not the least of the positive effects of rehabilitation is the saving of costs achieved by shortening the patient's time in hospital and reducing the number of working days lost.

Hereditary premenopausal breast cancer.

Less than 1% of breast cancers occur between the age of 20 and 30 years, but more than 50% of breast cancers under the age of 30 years are hereditary. Breast cancer mainly occurs sporadically, however, in 5 to maximally 10% of cases a genetic predisposition is present. Mutations in the already sequenced tumor suppressor genes BRCA1 and BRCA2 account for 60-70% of these hereditary breast cancers. The chromosomal location of BRCA1 is 17q21 and that of BRCA2 is 13q12-13. Screening procedures and possible prevention strategies for women with mutations in the BRCA1 and BRCA2 genes are discussed. They include the use of tamoxifen.

An unusual case of systemic lupus erythematosus, lupus nephritis, and transient monoclonal gammopathy.

A 23-year-old female patient suffering from active systemic lupus erythematosus (SLE) was treated with azathioprine (2 mg/kg per day) and prednisone. Lupus nephritis class III with increasing proteinuria developed 28 months after disease onset. Treatment was switched to monthly pulse cyclophosphamide administered intravenously for 6 months (total dose 6.3 g), followed by oral azathioprine and low-dose prednisone to maintain partial remission. Eight months later, the patient developed an acute exacerbation of SLE with fever, proteinuria of 9.1 g/day, pancytopenia, and cerebral involvement with cephalgias and a grand mal seizure. She responded well to high-dose corticosteroids (500 mg prednisolone pulses over 3 days, i.v.) and was azathioprine switched from to methotrexate (12.5-15 mg per week). Under this treatment, lupus activity gradually decreased and the patient felt well again. Five years after the initial diagnosis of SLE, a rapidly increasing immunoglobulin G-kappa type (IgG-kappa) monoclonal gammopathy developed, reaching a maximal serum paraprotein concentration of 73.5 g/l. Bone marrow biopsy revealed 15% of moderately abnormal, highly differentiated plasma cells arranged in small clusters and expressing IgG-kappa. No bony lesions were detectable on skeletal radiographs. Pulses of dexamethasone (40 mg) were administered and led to a transient decrease of paraproteinemia to a minimum of 31.9 g/l, followed by an increase to 62 g/l. At that point, high-dose chemotherapy supported by autologous stem cell transplantation was considered. Due to an intermittent pneumococcal septicemia, methotrexate was discontinued and dexamethasone was replaced by 5-10 mg cloprednol. At this point, totally unexpectedly, the paraprotein decreased spontaneously without any further cytostatic treatment and was no longer detectable 1 year later. Concomitantly, plasma cell counts in bone marrow biopsies fell to below 5%. As SLE remained inactive, the patient became pregnant and gave birth to a healthy child. During late pregnancy, SLE activity flared up with rising proteinuria and blood pressure. Therefore, after delivery, cyclophosphamide (100 mg/day, orally) was readministered for 4 months, resulting in an improvement of kidney function with stable proteinuria of 1-2 g/l to date. Paraproteins are no longer detectable. In conclusion, this case report documents the rare event of transient paraproteinemia in a patient with SLE. A self-limiting regulatory defect in the control of a terminally differentiated B-cell clone may be the origin of this phenomenon.

Bronchiolitis obliterans organising pneumonia and primary biliary cirrhosis-like lung involvement in a patient with primary biliary cirrhosis.

A 55-year-old woman with a 6-year history of primary biliary cirrhosis presented with an acute onset of fever, dyspnoea, crackles over both lower lung fields, and diffuse interstitial and bibasilar patchy pulmonary opacities. After exclusion of an infectious aetiology, an open lung biopsy was performed which revealed two histopathological features: (1) bronchiolitis obliterans organising pneumonia and (2) lympho-histiocytic interstitial pneumonitis and destructive bronchiolitis. Treatment response to corticosteroids and azathioprine followed a bimodal pattern with immediate resolution of her initial presenting symptoms and late resolution of residual gas exchange defects.

[Interdisciplinary group therapy for fibromyalgia]. / Interdisziplinäre Gruppentherapie für die Fibromyalgie.

Fibromyalgia is present in 2% of the general population and leads to impairment by chronic pain and fatigue. It does not improve without therapy directed at the symptoms of fibromyalgia. We describe our interdisciplinary group treatment for patients with fibromyalgia. They received a physical examination, ergometry and psychometric tests both at admission and before discharge, and they were questioned to the degree and localization of their pain, to fatigue, sleeping disorders and functional symptoms. Therapy included information about fibromyalgia, learning of coping strategies, relaxation and endurance training. Our results show that our interdisciplinary group treatment is effective for fibromyalgia and improves anxiety, depression and well being after a period of 5 weeks of in-patient rehabilitation.

Renal diseases in ankylosing spondylitis: review of the literature illustrated by case reports.

Ankylosing spondylitis (AS) can be accompanied by extraarticular manifestations in the cardiovascular, pulmonary, neurologic and renal organs. Secondary renal amyloidosis is the most common cause of renal involvement in AS (62%) followed by IgA nephropathy (30%), mesangioproliferative glomerulonephritis (5%) as well as rarely membranous nephropathy (1%), focal segmental glomerulosclerosis (1%) and focal proliferative glomeruleonephritis (1%). Treatment associated nephrotoxicity may result from non-steroidal anti-inflammatory drugs or disease modifying agents. The purpose of this paper was to alert for the possibility of renal damage in AS and to analyse the frequencies of different etiologies of renal involvement. Two typical case reports of renal involvement in AS are presented to illustrate the clinical course of such patients. Renal side effects and possible pre-existing renal diseases should be taken into account while choosing the appropriate medication for patients with AS.

Adhesion and migration are differentially regulated in hematopoietic progenitor cells by cytokines and extracellular matrix.

The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin-Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on beta1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1alpha, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-beta1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that beta1-integrin-mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of beta1-integrins in hematopoietic progenitor cells.

Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia.

Muscle tissue oxygen tension was measured by a polarographic oxygen fine-needle probe, and inorganic phosphate and creatine phosphate spectra were recorded using magnetic resonance spectroscopy in patients with chronic low back pain and in patients with fibromyalgia. Results were compared with healthy controls. The tissue oxygen tension was markedly higher in those with tense muscles than in normal subjects. Magnetic resonance spectra for inorganic phosphate were higher in patients demonstrating muscle contraction, and intracellular pH was shifted in the alkaline direction in cases with increased muscle tension. Results show that hypoxia is not the result of increased muscle tension, as was thought previously, but results from oversupply of oxygen demanded by the muscle, leading to increased capillary perfusion and rising oxygen tension.

Case report and review of the literature. Fatal pulmonary complication in ankylosing spondylitis.

A 44-year-old non-smoking patient with longstanding ankylosing spondylitis presented in marked respiratory distress with tachypnea, fever, cough, greenish sputum, night sweats, dyspnea and weight loss. Computed tomography showed traction bronchiectases and cavities associated with scarring. The findings were most pronounced in the upper lobes which contained multiple cavities up to 8 cm in diameter harboring fungus balls. The superior segment of the left lower lobe showed two additional cavities. Tuberculosis and atypical mycobacteria were ruled out. Antibiotic therapy resulted in transient improvement. Five months after this acute exacerbation the patient expired from massive haemoptysis. Pulmonary fibrosis is a rare manifestation of ankylosing spondylitis, may be complicated by infection and haemorrhage and determine the dismal prognosis of these patients.

Cerebral aneurysm in relapsing polychondritis.

A 51-year-old woman with relapsing polychondritis involving auricular and nasal cartilage, hearing loss, vasculitic skin lesions and a cerebral aneurysm of the posterior cerebral artery is described. Cerebral aneurysm is a rare manifestation of relapsing polychondritis which to our knowledge has not yet been described.

Stimulation of growth of human malignant lymphoma and lymphoid leukemia cells in vitro.

We have analyzed cultures of malignant lymphoma cells and cells from patients with acute lymphoid leukemia in methylcellulose for their ability to from colonies. Clonogenic growth was examined in the presence or absence of fetal calf serum (FCS), platelet-poor plasma (PPP), medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM), or irradiated allogeneic bone marrow stroma cells. Cells from 25 lymphoma patients--17 with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD)--and from 19 patients with acute lymphocytic leukemia (ALL) were investigated. We show that colony growth can be obtained in a minority of cases (in 3 NHL, 5 HD, and 2 ALL) and that the use of FCS and allogeneic irradiated stroma cells may be required for optimal colony formation.

Palmar fascial thickening and contractures of fingers resembling arthritis--a paraneoplastic symptom?

A 59-year-old women presented with contractures of the fingers of both hands 11 months before a diagnosis of an ovarian carcinoma with paraaortic lymph node metastases was made. We suggest that the contractures, which were associated with palmar fascial thickening and which clinically resembled arthritis, might have been a paraneoplastic sign.

Activated macrophages induce hemopoietic islands in the adult rat liver.

Focal hemopoiesis was induced in the liver of adult rats following treatment with glucan, a macrophage activator. Using endogenous peroxidase cytochemistry for identification of hemopoietic cell types, hemopoietic islands were studied by light and electron microscopy. Hemopoiesis in the islands was either restricted to the erythroid or myeloid lineage. Hemopoietic cells of various maturational stages frequently formed close contacts with macrophages. This indicates that activated macrophages exert a stimulatory effect on hemopoiesis by short-range action of humoral factors or by a close cell-to-cell-contact.

Effects of human bone marrow stroma on the growth of human tumor cells.

As some tumors metastasize frequently to marrow we modified the clonogenic assay for human tumor cell growth by culturing tumor cells in the presence of human bone marrow stromal cells. In a bilayer soft agar assay, human tumor cells which had been passaged in nude mice were plated in the agar overlayer on an underlayer containing a suspension of trypsinized human bone marrow stromal cells. These marrow stromal cells stimulated the growth of tumor cells in a dose-dependent fashion, with a growth peak at a stromal cell density of 5-10 x 10(5)/ml. The maximal stimulation of tumour cell growth was 13-fold. We evaluated clonal growth of six separate tumors of five different histological types (small and large cell bronchogenic carcinoma; mammary carcinoma; malignant melanoma; pleural mesothelioma) and demonstrated that in 9 of 11 experiments tumor cell colonies formed in the absence of stromal cells, but colony growth was markedly stimulated by stromal cells in every case. Stromal stimulation persisted after irradiation of the stromal cells with 10 Gy. Growth of five fresh human tumor samples was similarly stimulated by the presence of human bone marrow stromal cells. Tumor cell colonies were characterized morphologically by Pappenheim stain and immunologically for surface antigens by peroxidase-antiperoxidase immunostaining utilizing monoclonal antibodies (carcinoembryonic antigen 26/3/13 and 26/5/1, EMA, HEA125, Sam 2 and Sam 10) which detected epithelial cell antigens. Colonies consisted of cytologically malignant cells which expressed epithelial cell antigens. Thus, the tumor cell origin of colonies from mammary carcinoma and bronchogenic small cell, large cell, and adenocarcinoma was proven. This tumor stem cell assay permits further analyses of human tumor cell biology and may be useful for testing drug sensitivity.

[An unusual cause of mechanical ileus]. / Ungewöhnliche Ursache eines mechanischen Ileus.

A patient with the signs of mechanical ileus is reported. Past history of dilated cardiomyopathy with atrial fibrillation and the recent occlusion of the left renal artery suggested arterial mesenteric embolism. Celiacography ruled out mesenteric thromboembolism and vigorous enemas resulted in the delivery of the foreign bodies causing the mechanical ileus: 2 "10-Pfennig" coins.

Characterization of the in vitro stromal microenvironment of human bone marrow.

Utilizing long-term in vitro culture techniques, we characterized the cellular composition and functional attributes of the human in vitro bone marrow stromal microenvironment. Morphologic, specific cytochemical and immunologic methods demonstrated that the marrow stromal adherent layer (AL) reached confluency at two to three weeks, and was comprised of 60%-70% fibroblastic cells, 10%-20% endothelial cells, 10%-20% monocyte/macrophages and 5%-10% fat-laden adherent cells. These proportions of cell types persisted for at least three months concomitant with proliferation of CFU-gm and BFU-e. In contrast, umbilical cord blood cells did not form a stromal AL despite persistence of hemopoietic progenitor cell proliferation. These findings provide a basis for improved understanding of cellular interactions regulating hemopoiesis.

Fetal hemoglobin analysis of erythroid bursts in patients with chronic myelogenous leukemia (CML).

Early erythroid progenitors (BFUE) form colonies of mature progeny in culture. The development of hemoglobinized red cells within multilineage colonies (CFUGEMM) and erythroid bursts is dependent upon exogenously added erythropoietin and molecules released by hemopoietic subpopulations. Mixed colonies and erythroid bursts were grown from 3 patients with Ph' chronic myelogenous leukemia (CML). It was found that some mixed hemopoietic colonies and erythroid bursts did not require exogenously added erythropoietin. An increase of the plating efficiency of BFUE could be observed when erythropoietin was added. Erythroid bursts grown without added Ep from samples of the patients with chronic myelogenous leukemia have a higher probability to contain HbF than clones grown in the presence of Ep. The data support the view of a phenotypical heterogeneity among clonal descendents of a common ancestor as previously postulated for CML.