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Biomedical subjects

B Osterwalder

Publications and source records attributed to B Osterwalder.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin 2 and interferon alpha-2a do not improve anti-tumour activity of 5-fluorouracil in advanced colorectal cancer.

Treatment using a combination of 5-fluorouracil (5-FU), interferon-alpha (IFN alpha-2a) and interleukin 2 (IL-2) has been shown to mediate disease regression in selected patients with advanced colorectal cancer. This phase II study was designed to evaluate the anti-tumour activity and toxicity of the combination of IL-2, IFN alpha-2a and 5-FU in patients with advanced colorectal cancer. Forty-four patients with metastatic colorectal cancer were treated, predominantly on an outpatient basis, with subcutaneous IFN alpha-2a and IL-2 three times per week followed by once a week bolus intravenous 5-FU injections. There were six (14%) partial responses among the 43 evaluable patients [95% confidence interval (CI) 5-28%]. Twenty-four patients had stable disease (56%) and 13 patients (30%) showed progressive disease. The median time to progressive disease in 43 patients was 19 weeks (range 2-72 weeks) and in responders 34 weeks (range 24-30 weeks). The median overall survival was 47 weeks (range 2-85 weeks) and in responders 60 weeks (range 35-71 weeks). Treatment-related toxic effects included fatigue, nausea and vomiting. Granulocytopenia was the main reason for the dose reductions or treatment interruptions in 32 out of 44 patients. One patient died of toxicity due to renal failure. Serial assessments of immunophenotyping and cytolytic activities of peripheral blood lymphocytes did not show changes in the numbers of circulating natural killer (NK) cells or in the levels of NK and lymphokine-activated killer (LAK) cytolytic activities. This regimen of IL-2 and IFN alpha-2a with 5-FU has only modest anti-tumour activity in advanced colorectal cancer.

Adenocarcinoma↗
PubMed1995

Final report of a phase II study of interleukin 2 and interferon alpha in patients with metastatic melanoma.

Fifty-seven patients with metastatic melanoma were treated with interleukin 2 (IL-2) 7.8 MIU m-2 day-1 as a continuous infusion for 4 days combined with interferon alpha (IFN-alpha) 6 MIU m-2 day-1 subcutaneously on days 1 and 4. The cycle was repeated every 2 weeks for a maximum number of 13 cycles. Of the 51 evaluable patients, one (2%) achieved a complete and seven (14%) a partial response (total response rate 16%; CI 7-29%). Median time to progression and median survival were 2.5 and 11.3 months respectively. This regimen of IL-2 and IFN-alpha appeared to be only moderately active.

Adolescent↗
PubMed1995

Phase II study of subcutaneous rHu-interleukin-2 and rHu-interferon alpha-2a in previously treated patients with multiple myeloma.

BACKGROUND: Several studies have shown that interferon alpha as a single agent produces responses in multiple myeloma patients, and may produces responses in multiple myeloma of interleukin-2 (rHu-IL-2) in multiple myeloma models indicate that rHu-IL-2 may have a therapeutic effect. In this phase II clinical trial, we combined rHu-interferon alpha-2a (rHu-IFN-2a) and rHu-IL-2, to assess the feasibility, toxicity and response rate when this treatment was given as subcutaneous injections to previously treated patients with relapsed or refractory multiple myeloma. PATIENTS AND METHODS: Seventeen patients with measurable serum M protein or urine paraprotein were entered on the study. Three patients were refractory to first line treatment; fourteen had relapsed following response to prior treatment. rHu-IFN alpha-2a was given three times per week continuously. rHu-IL-2 was given three times per week for 6 weeks followed by a 2-week break from treatment. Patients were assessed for response and toxicity at 4-week intervals. RESULTS: All patients were eligible and evaluable for toxicity; two patients were invaluable for response because they did not complete 4 weeks of treatment. All response-evaluable patients had a best objective response of stable disease which lasted a median of 22 weeks and was maintained for over one year in 5 patients. Toxicity was tolerable and was typical of rHu-IL-2 and rHu-IFN alpha-2a; fever, chills or rigors and lethargy were nearly universal; local toxicity at the injection site, headache, anorexia, nausea and vomiting were also common. CONCLUSIONS: No objective responses in serum M protein or urine paraprotein levels were noted thus we do not recommend further study of this combination in myeloma.

Adult↗
PubMed1994

Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain.

BACKGROUND: Opioid and spinal monoaminergic agonists have distinct analgesic properties, which may potentiate each other. Tramadol has both opioid and monoaminergic agonist actions. This initial study compared the analgesic and toxic effects of tramadol and morphine in patients with strong cancer pain. PATIENTS AND METHODS: Pain control and side-effects with tramadol and morphine were compared in 20 cancer patients hospitalised for the treatment of strong pain. Doses of oral solutions of tramadol or morphine were individually titrated in the double-blind, randomized, cross-over study. Cross-over was after day 4, the day of statistical evaluation. RESULTS: The mean pain intensity (+/- SD) on a verbal rating scale (0 = none, 4 = unbearable) was similar with morphine (1.6 +/- 1.2, n = 17) and with tramadol (1.5 +/- 1.3, n = 16) on the fourth day of dosing. The mean daily doses on day 4 were 101 +/- 58 mg of morphine and 375 +/- 135 mg of tramadol, indicating a relative potency of 4:1 with oral dosing. The total number of side-effects per person was lower on the fourth day with tramadol (p < 0.05), as was the severity of nausea (p < 0.05) and constipation decreased with tramadol (p < 0.05). Three patients dropped out of the morphine group due to side-effects and 4 out of the tramadol group due to inadequate analgesia. Overall, 8 patients (40%) preferred morphine, 3 (15%) favoured tramadol and 9 (45%) expressed no distinct choice. Nurses rated pain control better with morphine (p < 0.03), but the tolerability of tramadol was judged superior (p < 0.002). CONCLUSIONS: In certain cancer patients with strong pain, tramadol achieved good pain control with fewer side-effects than morphine. The non-opioid mode of action may result in a different spectrum of analgesia and side-effects. Longterm studies are required to confirm this study of brief duration.

Administration, Oral↗
PubMed1994

Interleukin-2 therapy after allogeneic bone marrow transplantation for acute myelocytic leukemia: studies in a relevant rat model for AML.

One of the major problems in the treatment of leukemia with BMT remains leukemia relapse. It has generally been established that allogeneic BMT, compared with autologous BMT, gives rise to a graft-versus-leukemia reaction (GVLR), usually associated with GVHD. To explore a possible role for post-BMT immunotherapy, recombinant human IL-2 therapy has been studied in the Brown Norway acute myelocytic leukemia (BNML), a rat leukemia model relevant for human AML. The antileukemic efficacy of rhIL-2 therapy is studied applying different doses of rhIL-2 after syngeneic or allogeneic BMT. rhIL-2 treatment post-syngeneic BMT showed a small, borderline significant GVLR. Repeated rhIL-2 treatment after allogeneic BMT resulted either in no significant antileukemic effect or in lethal GVHD when 'low' or 'high' doses were administered, respectively. An intermediate dose, however, induced a significant GVLR without the induction of (lethal) GVHD. Transplantation of allogeneic rat BM, which contains only a few lymphocytes, does not result in a significant GVLR or GVHD and thus resembles human HLA-matched allogeneic T cell-depleted (TCD) BMT. In conclusion, from the rat studies presented it appears that the GVLR lost by TCD of the allogeneic graft, may be more than fully compensated by IL-2 treatment post-allogeneic TCD BMT.

Animals↗
PubMed1991

Cinnarizine for prevention of nausea and vomiting during platin chemotherapy.

The antiemetic efficacy of cinnarizine was assessed in 17 cancer patients receiving platin-based chemotherapy (cisplatin dose-range 30-160 mg, or carboplatin 270-600 mg) in a randomised, cross-over study. The patients were prophylactically given oral metoclopramide 3 x 1 mg/kg and lorazepam 2 x 1 mg with or without cinnarizine 3 x 75 mg. The antiemetic combination with cinnarizine prevented emesis completely on 51% of 35 days with chemotherapy and less than 3 emetic episodes occurred on 86% of the days, compared with 43% and 57% (p less than 0.01) without cinnarizine respectively. Severe nausea was significantly less frequent with cinnarizine and 59% of the chemotherapy days were without nausea, compared to 46% of the days without cinnarizine (p less than 0.05). Side-effects were uncommon and minor with both antiemetic regimens. The study suggests that addition of cinnarizine to metoclopramide and lorazepam improves antiemetic prophylaxis in low to medium dose platin-based chemotherapy.

Adult↗
PubMed1990

[Approach in metastasis with unknown primary tumor].

Metastases of an occult primary malignancy are quite common (5-10%), especially in lymph nodes, lung and bone. The search for the unknown primary is an intellectual challenge. Thorough history, meticulous physical examination, and economically and carefully directed additional investigations are the best methods of detecting a treatable malignancy. Even extensive standardized work-up, using all available laboratory and imaging techniques, may miss the primary tumor quite often and unnecessarily burden patients with poor prognosis. Prognostically and therapeutically distinct subgroups must be treated differently.

Algorithms↗
PubMed1990

Patient-controlled antiemesis for cancer chemotherapy-induced nausea and vomiting.

Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient-controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (greater than 3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of difficult-to-treat patients.

Adolescent↗
PubMed1989

[Icterus due to carotene associated with iron deficiency anemia].

We present 2 patients with carotenemia who also suffered from iron deficiency anemia. A causal relationship between the ingestion of excessive quantities of carrots and iron deficiency is postulated, since iron deficiency is known to be responsible for change of appetite (pica). A knowledge of this condition, which follows an indolent, reversible course, is necessary for the clinician mainly in view of the differential diagnostic aspects.

Adult↗
PubMed1989

Kinetics of cytomegalovirus IgG antibody following infusion of a hyperimmune globulin preparation in allogeneic marrow transplant recipients.

We investigated prospectively cytomegalovirus (CMV) IgG antibody kinetics following infusion of a CMV hyperimmune globulin preparation in 19 consecutive patients undergoing allogeneic bone marrow transplantation (BMT). CMV IgG against late antigen was measured by enzyme-linked immunosorbent assay. On a prophylactic hyperimmune globulin regimen (100 mg/kg body weight every 20 days), the mean half-life (t1/2) +/- SD of CMV IgG in seronegative patients with seronegative marrow donors was 19.7 +/- 7.9 days after the first infusion on day -7 before BMT, 24.9 +/- 12.5 days after the second infusion on day +13 after BMT, and 19.4 +/- 6.9 days after the third infusion on day +33. The t1/2 in individual patients showed a wide variation ranging from 10.9 to 47.6 days. A therapeutic high-dose hyperimmune globulin regimen (200-400 mg/kg body weight at 4-day intervals) given to five patients resulted in high serum levels of CMV IgG, which were maintained throughout therapy, even in two patients with severe intestinal graft-versus-host disease. The variation of CMV IgG kinetics between individual BMT recipients may contribute to the lack of protection from active CMV infection observed in some patients.

Adolescent↗
PubMed1988

[Ambulatory therapy with amphotericin B].

Therapy of systemic fungal infection with amphotericin B (AmB) must be continued for several months and is usually performed on an inpatient basis because of the risk of drug toxicity. Between 1983 and 1987 we treated 14 outpatients with a total of 164 AmB infusions. Side effects were generally mild and easy to control. Progressive impairment of renal function led to dose reduction and interruption of therapy in only one patient. Ambulatory therapy with AmB is feasible in an outpatient unit with adequate experience, and a significant reduction of treatment costs can result. Outpatient therapy is an acceptable alternative to inpatient treatment. Patients with malignant diseases under palliative therapy will profit most from the reduced duration of hospital stay.

Adolescent↗
PubMed1988

Hematological support in patients undergoing allogenetic bone marrow transplantation.

Bone marrow transplantation is impossible without effective support with blood components during the period of pancytopenia before graft function appears. We analyzed 39 patients with leukemia and three patients with severe aplastic anemia with regard to the pre- and postgrafting requirements for RBC and PLT transfusions. Overall a median of eight RBC and four PLT concentrates were necessary in all 42 patients after allogeneic BMT (ranges, 1-32 RBC and 1-11 PLT units). Requirements were identical irrespective of the underlying disease (ALL, AML, CML, SAA). Transfusion need for RBC and PLT concentrates increased in patients over 30 years old and with a major red blood group AB0 barrier between marrow donor and recipient. The presence of grade II-IV GvHD increased RBC requirements significantly, but not PLT requirements. In addition these patients were dependent on RBC transfusions for significantly longer periods. Only one patient required therapeutic granulocyte transfusions. In a CMV-negative patient with a CMV-negative marrow donor, who died of veno-occlusive disease, cytomegalovirus was transmitted inadvertently by a seropositive PLT concentrate in his final course. Our transfusion strategy included frozen deglycerolized RBC concentrates and single donor PLT concentrates, collected mainly from the marrow donor by a cell separator. All blood products were irradiated in vitro with 1500 cGy before transfusion. An optimal transfusion policy starting before BMT can contribute to successful bone marrow transplantation.

Adolescent↗
PubMed1987

[Myeloproliferative syndrome and acute febrile neutrophilic dermatosis (Sweet's syndrome)--a rare association].

The case is reported of a 73-year-old man presenting with a history arthralgia, conjunctivitis, fever and typical lesions of acute febrile neutrophilic dermatosis (Sweet's syndrome). Due to massive leukocytosis, an unclassifiable myeloproliferative disorder was later diagnosed. The disease responded well to hydroxyurea but only partly to steroids. The case demonstrates the necessity of close hematologic follow-up in Sweet's syndrome, since some 10% of patients develop hematologic malignancies weeks or months later.

Acute Disease↗
PubMed1987

[Simultaneous occurrence of hemophilia A and acute lymphatic leukemia].

In this paper the case of a man with haemophilia A is presented. At the age of 18 years an acute lymphatic leukaemia was observed. The case report demonstrates that even in the presence of a severe plasmatic coagulopathy an acute lymphatic leukaemia can be successfully treated with intensive chemotherapy, if the monitoring of the coagulation values and the substitution of antihaemophilic globulin and thrombocytes are guaranteed. Only 4 cases of haemophilia and acute leukaemia in the same patient are described in the literature. So we believe that the association of these two rare disorders is merely accidental.

Adolescent↗
PubMed1987

A comparison between ALG and bone marrow transplantation in treatment of severe aplastic anemia.

One hundred patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983. 28 patients had a HLA-identical sibling donor and were treated with bone marrow transplantation. 72 patients without a HLA-identical sibling donor were given antilymphocyte globulin followed by oral low dose androgen therapy. One and a half years to nine years after treatment 13 patients (46%) survive in the transplant group and 53 patients (74%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematological complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hemopoiesis: macrocytosis, mild granulocytopenia and mild thrombocytopenia. Relapse (11 of 72 patients) and clonal hematological disorders, such as paroxysmal nocturnal hemoglobinuria (4 patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. In spite of this we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplantation or antilymphocyte globulin.

Anemia, Aplastic↗