Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.

Anamnese und klinischer Befund: Untersuchungen: Therapie und Verlauf: Folgerung: History and clinical findings: Investigations: Treatment and course: Conclusion:

HISTORY AND CLINICAL FINDINGS:For nine years a 54-year-old woman had been suffering from worsening treatment-resistant cold-dependent purpura of the limbs as well as cutaneous ulcerations and arthralgia, which recently had occurred even at a even slight decrease in room temperature.INVESTIGATIONS:A special form of cryofibrinogenemia was identified by affinity-chromatographic separation of a plasma cryoprecipitate. From this cryoprecipitate a monoclonal antifibrinogen antibody (IgG-kappa) was isolated which, in the cold, formed a precipitating complex with fibrinogen. Paraproteinaemia was not demonstrated by conventional serum and plasma electrophoresis. There was no evidence of neoplasma.TREATMENT AND COURSE:Attempted treatment with steroids, fibrinolytic agents and intravenous cyclophosphamide was unsuccessful. But long-term repeated plasmaphereses and anti-immunoglobulin adsorption improved the symptoms. After 5 years of this treatment-14 years after onset of symptoms-the patient died of the consequences of fulminant pulmonary embolism.CONCLUSION:To establish the diagnosis of monoclonal cryofibrinogenemia it is necessary, first, to identify the cryoprecipitate in plasma; secondly, to undertake affinity-chromatographic separation of the cryoprecipitate with subsequent analysis of its components.

OBJECTIVE:To investigate whether human recombinant granulocyte colony stimulating factor (GCSF) is capable of inducing increased neutrophil granulocyte (polymorphonuclear leukocytes, PMN) counts in patients with systemic lupus erythematosus (SLE) associated neutropenia and refractory infections.METHODS:Nine patients with SLE associated neutropenia and concomitant refractory infections received a total of 12 cycles of 48 Mio U GCSF per day subcutaneously for an average of 6 days (range 1-17 days) as an adjunct to antibiotic treatment. In one case of impaired wound healing, longterm GCSF was applied over 148 days.RESULTS:In each case, the average PMN count increased distinctly within 2 days from 1.3 per nl (range 0.7-2.4) to 8.4/nl (3.2-19.4). Major adverse events were exacerbation of central nervous system symptoms in 2 patients and leukocytoclastic vasculitis in one.CONCLUSION:GCSF induces a rapid increase in PMN counts in patients with lupus associated neutropenia and normal or hyperplastic granulopoiesis. In 3 of 9 patients we observed a flare of lupus associated symptoms.

Intravenous pulse cyclophosphamide (Cy) is an established treatment for severe SLE and other autoimmune diseases. Peroral application on an outpatient basis would be easier, less costly, and impose less of a burden on patients. We studied the feasibility of peroral pulse Cy in 16 patients with SLE (n=12), pemphigus (n=2), glomerulonephritis and cerebral vaculitis (n=1 each). 795 oral Cy pulses (ranging from 285 mg/m(2) up to the intravenous dosage of 1000 mg/m(2)) were applied (mean dosage: 480 mg/m(2)), 95% on an outpatient basis. 77% of the pulses induced no side effects. Nausea or vomiting were observed in 22%, oral candidiasis and pneumonia once each. In 12 patients disease activity declined, with a mean drop in the SLE activity index (SLAM) of 30.5%. Neurological deficits in the cerebral vasculitis improved and one of the pemphigus patients experienced remission of cutaneous blistering. Provided there is good patient compliance and if frequent laboratory controls are carried out, peroral pulse Cy is a feasible option.

High-dose chemotherapy with subsequent transplantation of hematopoietic stem cells is currently being discussed as a new treatment option in severe cases of SLE and other autoimmune disorders. This review summarizes current theoretic considerations, experimental results, and clinical data. Present knowledge appears to indicate that autologous transplantation of purged peripheral blood progenitor cells is best able to balance long-term remission and an acceptable risk of side effects. Another possible option is allogeneic transplantation of purged peripheral blood progenitor cells.

Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases.

Nine patients with SLE-associated neutropenia and infections received 48 Mio U G-CSF per day sc. for 2-17 days as an adjunct to antibiotic treatment. Granulopoiesis was normal or hyperplastic in all cases. The mean granulocyte count increased within 2 days from 1.4 per nl to 11.4 per nl. Side-effects were exacerbating CNS symptoms in two patients and a case of leukocytoclastic vasculitis.G-CSF induced constantly a rapid and distinct increase of neutrophil granulocytes in lupus-associated neutropenia patients with normo- or hyperplastic granulopoiesis.

OBJECTIVE:To investigate the effect of high dose intravenous immunoglobulins (IVIG) in systemic lupus erythematosus (SLE).METHODS:Twelve patients with mildly to moderately active disease were given 30 g of sulfonated IVIG preparation on each of Days 1-4 and 21-24.RESULTS:Within 6 weeks the mean disease activity score, the Systemic Lupus Activity Measure (SLAM), declined from 7.33 (range 3-15) to 5.25 (range 0-10) (p < 0.01). In 9/12 patients the SLAM dropped by at least 2 points. In 3/12 patients the improvement lasted 5 to 12 months. Within 1 week after initiation of therapy most patients showed a decline in ds-DNA antibodies, whereas titers of antinuclear antibodies and complement proteins were not affected. The treatment was well tolerated, with the exception of transient hypotension in one patient.CONCLUSION:In this uncontrolled study, IVIG had temporary beneficial effects in mildly to moderately active SLE.