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Biomedical subjects

H Gamm

Publications and source records attributed to H Gamm.

At least 19 recordsLinked to original sources

[Pain assessment in invasive diagnostic procedures. Comparison of an eleven-point numerical rating scale and a six-point verbal rating scale for pain measurement in bone marrow puncture].

BACKGROUND AND OBJECTIVE: Pain measurement during diagnostic procedures is an accepted prerequisite for appropriate therapy. In this study, the agreement between rankings of pain intensity on a numerical and a verbal rating scale was analyzed. METHODS: Patients attending a haematological outpatient clinic who underwent bone marrow puncture were requested to assess pain intensity perceived during the procedure on a elen-point numerical and a six-point verbal rating scale. RESULTS: Analysis of patients' pain ratings in 263 bone marrow punctures showed a very good correlation between numerical and verbal rating scale (Spearman correlation coefficient 0,86). By means of a transfer instruction categories of the verbal rating scale were assigned to figures of the numerical rating scale (0 - no pain, 1 or 2 - mild p., 3, 4 or 5 moderate p., 6 or 7 severe p., 8, 9 or 10 - very severe and worst possible pain). The resulting transfer table showed a good agreement with a weighted kappa of 0.72 (95% confidence interval: 0.66-0.79). CONCLUSION: Both scales can be employed efficiently for pain assessment during diagnostic procedures. Verbal categories can be assigned to numerical values and vice versa numerical values to verbal categories. However, in view of the inter-individual variations it appears appropriate to re-assure pain perception with each patient in order to avoid over- or undertreatment.

Biopsy↗

Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL.

The purpose of this study was to evaluate feasibility and efficacy of Rituximab included into a sequential salvage protocol for CD20(+) B-NHL in relapse or induction failure. Twenty-seven patients with CD20(+) B-NHL in relapse or induction failure received Rituximab combined with DexaBEAM (R-DexaBEAM) for stem cell mobilization. Additional ex vivo selection of CD34-positive cells was performed using the CliniMacs device. Two doses of Rituximab were included in the high-dose therapy regimen (HDT). R-DexaBEAM was well tolerated and 26 of 27 patients mobilized sufficient numbers of CD34(+) blood stem cells. Application of R-DexaBEAM resulted in significant depletion of peripheral B cells. No treatment-related deaths occurred after HDT and all patients showed stable engraftment of hematopoesis. Combined immunodeficiency was observed post HDT and eight patients developed CMV antigenemia. Remission rate post HDT was 96% (CR, 24/26; PR, 1/26). Overall and progression-free survival (PFS) at 16 months post HDT (range 6-27) is 95% and 77%, respectively. With regard to histology, PFS was 71% in aggressive lymphoma (n = 11), 74% in indolent FCL (n = 10) and 100% in MCL (n = 5). The treatment protocol has proven feasible, with high purging efficiency and encouraging remission rates.

Adult↗

[Chloroma (granulocytic sarcoma, myeloblastoma). Clinical aspects and radiological diagnosis].

Six cases of granulocytic sarcoma are presented. A mediastinal chloroma and a tumor of the submandibular gland were observed with two patients as single sign of acute myeloic leukaemia. In one patient a chloroma appeared as first manifestation of acute myeloic leukaemia. Two patients exhibited the tumor as first symptom of a blastic crisis of chronic myelogenous leukaemia (femoral bone, lumbar spine). The sixth patient with a myelodyplastic syndrome showed a chloroma of the breast. Various radiological procedures were applied including plain radiography, MRT, CT and mammography. The results are compared with literature. Principles of therapy were supplemented.

Acute Disease↗

Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes.

Previous studies have shown that intravenous immunoglobulin (IVIg) therapy is useful prophylaxis against infection in patients with secondary hypogammaglobulinaemia due to a low-grade lymphoproliferative disease. This randomized double-blind study was undertaken to determine prospectively the dose regime required. 34 such patients received IVIg at either 500 or 250 mg/kg every 4 weeks for 1 year. There was no significant difference in the rates of serious infections between the two groups of patients, which were well matched for disease and laboratory parameters. The rates of infection seen were similar to those in IVIg groups of previous studies and strikingly different from those in the placebo group in the previously randomized placebo-controlled study.

Aged↗

Molecular analysis of the erythropoietin receptor system in patients with polycythaemia vera.

Erythropoietin (EPO) is a potent regulator of the viability, proliferation and differentiation of erythroid progenitor cells. Its effect is mediated by binding to the erythropoietin receptor (EPO-R), a member of a new cytokine receptor family. Alterations of the EPO/EPO-R system have recently been shown to be involved in the pathogenesis of familial erythrocytosis and polycythaemia vera (PV). In order to define whether genetic changes in the EPO-R gene and its ligand play a role in the development of PV, the structure and expression levels of the EPO-R and EPO genes were examined in samples from bone marrow and/or peripheral blood mononuclear cells of 24 patients with PV. As expected, EPO serum levels were low and no detectable level of EPO mRNA was found by reverse polymerase chain reaction (RT-PCR) in the peripheral blood mononuclear cells of our PV patients. To search for structural alterations of the EPO-R, cDNA samples were subjected to PCR and SSCP analysis as well as sequencing. Heterogenous expression of EPO-R mRNA was observed without any structural changes, as revealed by RT-SSCP analysis using overlapping primers spanning the whole coding region of the EPO-R gene. Structural integrity of the EPO-R was further confirmed by sequencing of cloned PCR products. These data suggest that the mechanisms for the development of PV do not involve structural changes of the EPO-R gene.

Adult↗

Intravenous immune globulin in chronic lymphocytic leukaemia.

The most common complication of chronic lymphocytic leukaemia (CLL) is infection, which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia. Intravenous immune globulin (IVIG) has been shown to be a useful prophylactic therapy against infections in such patients. A randomized, double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required. There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG.

Agammaglobulinemia↗

Amyloidoma of the gasserian ganglion as a cause of symptomatic neuralgia of the trigeminal nerve: report of three cases.

Three cases of symptomatic neuralgia of the trigeminal nerve due to an amyloidoma in the gasserian ganglion are described. The correct diagnosis was not made prior to histological examination of the surgical biopsy specimens. Medical history and clinical observation led to the diagnosis of a malignant process of the nasal cavities in the first patient; of an inflammatory dental focus in the second patient; and of multiple sclerosis in the third patient. CT findings were normal in cases 1 and 2; in case 3, a schwannoma was suspected from the CT appearances. In case 1, MRI had not been performed; in cases 2 and 3, MRI revealed a tumour mass which was also considered to be a schwannoma. Histologically, the tumours consisted of masses of amyloid deposits which had largely replaced the pre-existing ganglionic cells and satellite cells. Electron microscopy confirmed the fibrillar structure of the deposits. Immunohistochemistry and immunocytochemistry revealed the amyloid to belong to the AL-lambda subtype.

Adult↗

Natural inhibitors of T-cell activation in Hodgkin's disease.

Secondary immunodeficiency is frequently observed in Hodgkin's disease (HD) and is due in part to impaired T-cell function. Using monoclonal antibodies that bind to triggering molecules of human T lymphocytes (CD3/Ti antigen receptor; CD2 E-rosette receptor) and exert functional effects on T-cell activation, we have investigated in vitro immune responses of circulating lymphocytes from patients with HD in progression (n = 9) and in remission (n = 14). In patients with progressive HD, a severe dysfunction of the alternative CD2-mediated T-cell activation pathway was detected (49.3 +/- 14.2 v 9.4 +/- 5.1 cpm x 10(-3), in controls, P less than .01; n = 9) that parallels the reduced capacity of T lymphocytes to form rosettes with sheep red blood cells. Diminished alternative pathway activation in HD is not only due to a defect at the cellular level but also due to soluble mediators in the patients' plasma. Plasma from patients in progression markedly reduces CD2 mediated activation (P less than .01). These activities interfere, at least in part, with CD2/CD58 interactions and, therefore, reduce T-lymphocyte triggering through this amplifier mechanism.

Adult↗

Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review.

Chronic lymphocytic leukemia (CLL) is a disorder with multiple defects leading to an increased susceptibility to infection. Hypogammaglobulinemia is present in about 20% to 70% of patients with CLL. Intravenous immunoglobulin (IVIG) supplementation (400 mg/kg body weight every 3 weeks) prevented bacterial infections in these patients. An ongoing study is being conducted to compare doses of 250 mg/kg/mo with those of 500 mg/kg/mo in 36 patients included so far. As of this writing, the rate of infection in the two treatment groups was not significantly different, and no substantial loss of protection against bacterial infection was found in the lower-dose group. It seems likely that the lower dose is almost as effective as the standard therapy. If this is so, cost savings would be substantial.

Humans↗

Phase I trial of recombinant human tumour necrosis factor alpha in patients with advanced malignancy.

A phase I clinical trial was conducted with recombinant human tumour necrosis factor alpha (rhTNF-alpha) in 62 patients with advanced malignancy refractory to previous standard therapy. rhTNF-alpha was given as a 30 min infusion twice a day at 6 h intervals. A total of 10 different dose levels was escalated in cohorts of 6 patients ranging from 2.5 to 200 micrograms/m2 twice a day for 5 days every second week for a total of 8 weeks followed by a 4-week observation period. Major side-effects of TNF-alpha therapy, seen in almost all patients studied, were fever and chills. As dose-limiting side-effects hypotension and liver toxicity were recorded in 4 of 5 patients treated with 200 micrograms/m2 twice a day. Pharmacokinetic studies revealed a TNF-alpha serum half-life of 13 to 25 min, a dose-dependent decrease in TNF clearance, and a dose-dependent increase in the area under the time/concentration curve. No anti-TNF-alpha antibodies could be detected, except in 1 patient. Tumour response to TNF treatment was poor. Only in 3 of 57 evaluable patients was partial tumour regression observed.

Adolescent↗

MACOP-B chemotherapy for the treatment of high grade and intermediate grade non Hodgkin's lymphoma.

Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group with relapsed disease 14% had PR and 14% had progressive disease (PD). At a medium follow-up of 12 months (range 1 month to 33 months), 74% of patients with de novo NHL continued to be in CR whereas the continuous CR rate in patients with relapsed disease was 35%. Overall survival after 30 months of observation for the patient group with de novo NHL was 75% and 40% for patients with relapsed NHL. The mean duration for completion of the projected 12 chemotherapy cycles, given in weekly intervals, was 12.9 and 13.5 weeks in upfront or salvage therapy, respectively. With low incidence of major toxicities, application of drugs on an outpatient basis, and high efficacy, MACOP-B shows substantial advantages for therapy of de novo and relapsed NHL.

Adult↗

Erythropoietin prevents chemotherapy-induced anemia: case report.

A thirty-seven year old male patient with heavily pretreated metastatic testicular carcinoma received escalating doses of recombinant human erythropoietin (EPO) before and throughout chemotherapy. Whereas previous chemotherapy regimens repeatedly caused anemic situations in this patient (hemoglobin (HB) 7.0 g/dl requiring multiple transfusions of red blood cells), EPO given as an i.v. bolus injection at escalating doses of 150 to 300 U/kg body weight (BW) twice/week, starting two weeks prior to the identical myelosuppressive treatment protocol, maintained HB at levels above 8.8 g/dl and thus obviated the need for erythrocyte transfusion. EPO was discontinued after 9 weeks of administration when the patient had achieved a hematocrit (HCT) of 41.1% and a HB of 12.7 g/dl. However, erythropoiesis continued to recover for the next 7 weeks reaching a HCT of 42.4% and a HB of 14.3 g/dl, although the next identical chemotherapy cycle had been given within this period. Along with the rise in HB, ferrokinetics changed significantly as measured by serum ferritin, which was reduced to one third at the end of EPO therapy after only 9 weeks (from 979 ng/ml to 320 ng/ml). No side effects due to EPO administration occurred. These data provide first evidence for efficacy of EPO in chemotherapy-induced anemia and may open new avenues for its clinical application.

Adult↗

Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration.

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.

Aged↗

Hematopoietic growth factors in oncology.

Hematopoietic growth factors, or hemopoietins, are peptide hormones produced by peripheral blood cells, bone marrow stroma, as well as several other cell types, such as endothelial cells and fibroblasts. Hemopoietins play a central role in regulating peripheral blood cell number and function. By recombinant DNA technology, several of these factors, also called colony-stimulating factors (CSF) or interleukins, are now available in such quantities to allow clinical evaluation. First experiences in clinical trials show that these peptides are capable of stimulating production of various cell types of the peripheral blood by stimulation of bone marrow progenitor cells without significant toxicity for the patient under treatment. Treatment of renal anemia by erythropoietin and reduction of chemotherapy-induced myelosuppression by G- and GM-CSF are already defined indications for these hemopoietins. Further studies are under way to test the indication of these factors in other clinical situations as well as studies investigating the biology, pharmacology, and clinical efficacy of interleukin 3 (IL-3).

Hematopoietic Cell Growth Factors↗

A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma.

Recent preclinical and clinical studies that have demonstrated antitumor activity of high-dose recombinant interleukin-2 (rIL-2), and animal models that demonstrated a synergistic effect of low-dose cyclophosphamide, led us to study rIL-2 (Cetus Corp., Emeryville, Calif) in a phase II clinical trial in combination with low-dose cyclophosphamide in 32 patients, 18 with malignant melanoma and 14 with renal cell carcinoma. rIL-2 was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for 2 x 5 days in cycles II and III respectively; if tolerated, the dose was increased to a maximum of 6 x 10(6) U m-2 day-1; the cycles, separated by 1 week treatment-free intervals, were preceded each by a single i.v. bolus of cyclophosphamide at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever that required dose reduction during the first cycle in one-half of the patients. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor antitumor activity. No remission was achieved in patients with renal cell carcinoma, and 15% of melanoma patients showed objective responses (partial response + minor response).

Adult↗

A multicenter trial of interleukin-2 and low-dose cyclophosphamide in highly chemotherapy-resistant malignancies.

The anti-tumor activity of high-dose recombinant interleukin-2 (IL-2) has been demonstrated in several recent preclinical and clinical studies. In an attempt to study possible synergistic effects with low-dose cyclophosphamide (CYC), a phase II clinical trial was initiated in 32 patients, 18 with malignant melanoma (MM) and 14 with renal cell carcinoma (RCC). The recombinant IL-2 (Cetus Corp., Emeryville, Ca, U.S.A.) was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for five days twice in cycles II and III, respectively; if tolerated, the dose was escalated to a maximum of 6 x 10(6) U/m2/day; the cycles, separated by 1-week treatment-free intervals, were each preceded by a single i.v. bolus of CYC at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever requiring dose reduction in half of the patients during the first cycle. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor anti-tumor activity. No objective responses were achieved in patients with RCC and a 15% remission rate (PR + MR) was seen in melanoma patients.

Antineoplastic Combined Chemotherapy Protocols↗