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Biomedical subjects

E Hippe

Publications and source records attributed to E Hippe.

At least 37 records · Page 2Linked to original sources

Renal function in newly diagnosed multiple myeloma--a demographic study of 1353 patients. The Nordic Myeloma Study Group.

This study describes the occurrence of renal failure among 1353 newly diagnosed cases of multiple myeloma. Renal function was evaluated by serum creatinine concentration in 1353 cases, 31% of whom had renal failure at the time of diagnosis. In 1206 cases an estimation of creatinine clearance was made. When renal failure was defined by using creatinine clearance estimation, 49% had renal failure at the time of diagnosis. Renal failure was present in 24% of patients with an M component of IgG-, 31% of IgA- and 100% of IgD-type. 52% of patients with light chain disease had renal failure. The frequency of renal failure was similar in lambda- and kappa-light chain disease. Patients with a high excretion of Bence Jones protein in the urine (> 10 g/24 h) had renal failure significantly more often than patients with lower excretion. Renal failure was related to advanced disease; 41% of patients with stage III (Durie-Salmon) disease had renal failure. Renal failure was found in 45% of patients with hypercalcaemia. When estimated creatinine clearance was used as a predictor of renal function, the same trends were found as mentioned above. In addition, the proportion of patients with renal failure was found to increase with advancing age.

Adult↗

[Renal insufficiency in myelomatosis. Causes and treatment].

Renal failure is a frequent complication in multiple myeloma and it is present in about 50% of patients with newly-diagnosed multiple myeloma. Renal failure at the time of diagnosis has earlier been associated with a bad prognosis, but a better prognostic factor is the response to chemotherapy. In general, it is important to distinguish between 1) renal insufficiency at the time of diagnosis, 2) acute renal insufficiency and 3) chronic renal insufficiency developing during the course of the disease. The patients in the first two groups are treated with intensive therapy which is long-lasting (median four to six weeks). The improved function of the kidney is correlated to an improved survival. Patients developing chronic renal insufficiency late in the course of the disease should receive palliative therapy. The most important factors that provoke acute renal insufficiency are dehydration, hypercalcaemia and/or infection, but renal insufficiency is also provoked by the use of nephrotoxic drugs, hyperuricaemia and/or hyperviscosity. Chronic renal insufficiency is provoked by deposits of light chains, infiltration by plasma cells or deposits of amyloid. The treatment consists of elimination of the provoking factors and start of chemotherapy.

Acute Kidney Injury↗

[Daily single-dose aminoglycoside administration. Therapeutic and economic benefits].

Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity. Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Pharmacokinetic and microbiological data support this finding. Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing. The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Recommendations for once-daily dosing of netilmicin are given.

Aminoglycosides↗

Hypereosinophilic syndrome treated with alpha-interferon and granulocyte colony-stimulating factor but complicated by nephrotoxicity.

A 34-year-old male with hypereosinophilic syndrome (HES) and cardiac complications was treated with recombinant human alpha-interferon (rhIFN) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the attempt to suppress the eosinophilic cell clones and stimulate the neutrophil myelopoiesis in the bone marrow, respectively. After 1 month of pretreatment with rhIFN, rhG-CSF was administered daily for 22 days. Within a few days the combined treatment with rhIFN and rhG-CSF was followed by a marked increase in absolute neutrophil count but complicated by abdominal pain and an increase in plasma creatinine and blood urea nitrogen. The renal failure persisted when rhIFN therapy was stopped but resolved after discontinuing rhG-CSF. The pathogenesis of this reversible renal involvement needs further investigation. In that hematological improvement in vivo as well as in vitro followed the administration of rhIFN and rhG-CSF, a role for combined therapy with these cytokines may be advocated. However, caution with regard to kidney function should be taken with this combination therapy.

Adult↗

Recombinant human granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes.

The purpose of this study was to improve erythropoiesis in patients with anemia due to myelodysplastic syndromes (MDS). We treated 13 patients first with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 6 weeks, then with recombinant human erythropoietin (rhEpo) and rhGM-CSF for the next 12 weeks. Five patients had refractory anemia (RA), 3 refractory anemia with ringed sideroblasts (RAS), and 5 refractory anemia with excess of blasts (RAEB). Ten patients were transfusion-dependent at the time of inclusion. Eleven patients completed this phase II study. Five responded with an increase in hemoglobin level (3 patients) or a reduction in transfusion requirement (2 patients). We registered no response in the remaining 6 patients during treatment. Patients responding to combined treatment had relatively low concentrations of plasma Epo and plasma ferritin before treatment with rhEpo and a normal karyotype throughout the study. Long-term bone marrow cultures did not predict the response. Still, responders seemed to have a higher number of colony-forming progenitors than nonresponders. In conclusion, combined therapy with rhGM-CSF and rhEpo may stimulate hematopoiesis and correct or improve anemia in some patients with MDS.

Aged↗

Diurnal variations of serum erythropoietin in trained and untrained subjects.

The diurnal variations of serum-erythropoietin concentration ([s-EPO]) were investigated in six physically trained (T) and eight untrained (UT) men. The T subjects had a higher mean maximal oxygen uptake than UT subjects [75.7 (SEM 1.6) ml.min-1.kg-1 versus 48.3 (SEM 1.4) ml.min-1.kg-1, P < 0.0001] and a lower mean body mass index [BMI, 21.7 (SEM 0.7) kg.m-2 versus 24.4 (SEM 0.6) kg.m-2, P = 0.02]. Each subject was followed individually for 24 h as they performed their normal daily activities. Venous blood samples were collected from awakening (0 min) until the end of the 24-h period (1440 min). Both T and UT had a nadir of [s-EPO] 120 min after awakening [10.0 (SEM 0.3) U.l-1 versus 11.5 (SEM 2.1) U.l-1, P > 0.05]. The UT and T increased their [s-EPO] to peak values at 960 min and 960-1200 min, respectively (ANOVA P = 0.03) after awakening [UT: 18.4 (SEM 2.8) U.l-1; T: 16.2 (SEM 2.5) U.l-1, P > 0.05]. The mean 24-h [s-EPO] were 14.5 (SEM 1.0) U.l-1 and 14.9 (SEM 0.9) U.l-1 in T and UT, respectively (P > 0.05). The individual mean 24-h [s-EPO] were not correlated to body mass, BMI or maximal oxygen uptaken. Significant diurnal variations in [s-EPO] occurred in these healthy subjects irrespective of their levels of physical activity.

Analysis of Variance↗

The effect of short and long duration exercise on serum erythropoietin concentrations.

The effects of short and long duration exercise on serum erythropoietin concentrations [EPO]s were studied in seven male cross-country skiers of national team standard and eight male marathon runners, respectively. The short duration exercise was performed as 60 min of cycling at an intensity of 80%-95% of maximal heart rate. Arterial blood oxygen saturations monitored by pulse-oximetry remained unchanged throughout exercise. The partial pressure of O2 at which haemoglobin was half-saturated with O2 calculated from forearm venous blood gas tension and blood O2 saturation, and the erythrocyte 2,3-diphosphoglycerate did not change significantly during the exercise. Blood lactate concentrations were increased at the end of exercise [from 1.3 (SEM 0.1) to 3.6 (SEM 0.3) mmol.l-1]. The [EPO]s determined (by enzyme-linked immunosorbent assay) pre-exercise, 5 min, 6 h, 19 h, and 30 h after the exercise were unchanged [from 16.1 (SEM 2.6) to 19.1 (SEM 3.2), 17.9 (SEM 3.0), 17.0 (SEM 2.5), and 18.6 (SEM 2.9) U.l-1, respectively]. The [EPO]s were not correlated to the earlier parameters. The long duration exercise consisted of habitual training, a 3 week break from training followed by 2 and 4 weeks of re-training. The [EPO]s, body fat (BF), and serum free-testosterone concentrations determined at the end of each period remained unchanged. The maximal oxygen uptakes were decreased after the break from training and increased during retraining (P = 0.04). Body mass (mb) increased after the break in training (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Nordic Myeloma Study Group (NMSG).

One-hundred-and-fifty-one patients with previously untreated multiple myeloma were allocated to treatment with either NOP regimen (mitoxantrone 16 mg/m2 and vincristine 2 mg day 1 and prednisolone 250 mg day 1-4 and 17-20) or M+P regimen (melphalan 0.25 mg/kg and prednisolone 100-200 mg/day day 1-4). Both regimens were repeated every 4 weeks and were scheduled for 1 year. Seventy-seven patients were treated with NOP and 74 patients with M+P. No major clinical differences were recorded between the groups before treatment. Sixty percent of the patients responded (CR+PR) to NOP versus 64% to M+P (NS). The time to progression was 16 months (95% C.L. 14-51) in the NOP group versus 21 months (95% C.L. 15-27) in the M+P group (NS). The median survival was 14 months (7-21) in the NOP group and 31 months (21-43) in the M+P group (p = 0.02). NOP was significantly more toxic than M+P. Seven patients treated with NOP died due to infection and neutropenia and 1 patient died of cardiac toxicity, in contrast to 1 death due to infection and neutropenia in the M+P group. Gastrointestinal toxicity was acceptable in both groups. In conclusion, NOP was inferior to M+P as primary treatment of multiple myeloma.

Adult↗

[Pernicious anemia. A study of initial forms of the disease and diagnostic significance of determination of the intrinsic factor antibody and parietal cell antibody].

In a prospective study of thirty five consecutive patients with decreased plasma cobalamine (P-Cbl), twenty-two (63%) were diagnosed as having pernicious anaemia (PA) (no age or sex differences) on basis of the B12-absorption test and/or megaloblastic changes in the bone marrow. In this group ten patients were anaemic (six of whom were characterized as macrocytic), sixteen of nineteen examined had megaloblastic changes in the bone marrow, and all of thirteen examined had achlorhydria with positive correlation to Parietal Cell Antibodies (PCA). Two patients with PA had normal Cbl-absorption and two had malabsorption at the time of diagnosis. Twenty-one patients (95%) had PCA and thirteen (59%) were Intrinsic Factor Antibody (IFAb) positive. Three patients IFAb-seroconverted within a year. Among the remaining thirteen patients (37%), one had PCA but not IFAb and three were IFAb-positive all of whom had normal Cbl-absorption. Of the three patients with IFAb one had also PCA, one IFAb-seroconverted within three months, and one had microcytic anaemia with iron depleted bone marrow due to coecal cancer. Among twenty two healthy adult controls four (18%) had PCA while none had IFAb. This investigation shows that at the debut half of PA patients (55%) do not have anaemia, some have normal Cbl-absorption and some have malabsorption. 95% have PCA and 59% have IFAb. So, IFAb-negative PA is often seen (41%) and seroconversion can take place. Diagnosis is even more reliable, when achlorhydria is present in PCA-positive persons. Healthy PCA-positive persons are probably predisposed to develop PA. Patients with cbl-deficiency, IFAb and/or PCA must be considered as having latent PA even if they have normal haemoglobin and normal Cbl-absorption. These patients should be followed and, in case of anaemia or signs of neuropathia, treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Pernicious↗

[Hematopoietic growth factors in primary and therapy-related bone marrow insufficiency].

This investigation is retrospective and comprises 20 patients with bone-marrow insufficiency. During the period 1.4.1988-1.3.1991, these patients were treated with erythropoietin (Epo), the granulocyte-macrophage-colony-stimulating factor (GM-CSF) or the granulocyte-colony-stimulating factor (G-CSF). Thirteen patients had primary bone-marrow insufficiency: six had the myelodysplastic syndrome, three had primary myelofibrosis, two aplastic anemia and two myelomatosis. On account of dominating symptoms of anemia, five patients received Epo while eight received GM-CSF as part of an extensive clinical trial of this preparation. Seven patients with relapse of the haematological malignant disease had bone-marrow insufficiency and pancytopenia secondary to intensive chemotherapy/irradiation: four of these patients received GM-CSF and two received G-CSF with the object of increasing bone-marrow regeneration and to render further chemotherapy possible. One patient received GM-CSF with the object of improving bone-marrow function after autologous bone-marrow transplantation. Treatment with Epo for ten months combined with treatment with interferon for six months resulted in normalization of the haemoglobin concentration in one patient with bone-marrow insufficiency on account of primary myelofibrosis. Treatment with Epo for briefer periods in lower doses was without effect in four other patients with primary bone-marrow insufficiency. Treatment with GM-CSF and G-CSF resulted in neutrophil leukocytosis in 12 out of 15 patients (80%) and, in six out of 14 patients (43%), increased marrow cellularity was demonstrated by means of histological examination of the bone-marrow. One patient showed normal haemoglobin levels during treatment with GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autoimmune reactions in patients with M-component and peripheral neuropathy.

A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, Waldenström's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.

Adult↗

Bolus therapy with mitoxantrone and vincristine in combination with high-dose prednisone (NOP-bolus) in resistant multiple myeloma. Nordic Myeloma Study Group (NMSG).

In a phase II study, 58 patients with resistant multiple myeloma (MM) were treated with a combination chemotherapy (NOP-bolus regimen) consisting of mitoxantrone (16 mg/m2 for the first 25 patients and 12 mg/m2 for the subsequent 33), vincristine (2 mg), both as bolus injections on day 1 and prednisone (250 mg/d on d 1-4 and 17-20). In patients greater than 70 years of age, the mitoxantrone dose was reduced to 12 mg/m2 or 8 mg/m2, respectively. The treatment was repeated every 4 weeks. A response (greater than 50% reduction in M component) was obtained in 26% of the patients and a minor response (clinical improvement but less than 50% reduction in M component) in another 21%. Median response duration was 27 wk and median survival for all patients was 25 wk. There were no differences in response rate or duration between patients receiving the high or low mitoxantrone dose, but patients in the low-dose group had fewer serious infections.

Adult↗

Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study. The Nordic Myeloma Study Group (NMSG)

In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.

Adult↗

Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases.

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.

Adolescent↗

Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

Aclarubicin↗