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Biomedical subjects

V Jønsson

Publications and source records attributed to V Jønsson.

At least 19 recordsLinked to original sources
PubMed2005

CLL family 'Pedigree 14' revisited: 1947-2004.

The notion that inherited predisposition contributes to the development of haematological malignancies is generally thought of as being a relatively new idea. However, Videbaek made a clear enunciation of such a hypothesis in 1947, from a study of tumour incidence in relatives of patients with different leukaemias. To gain further insight into inherited susceptibility to chronic lymphocytic leukaemia (CLL), we followed up the descendants of Videbaek's 'Pedigree 14' series of families. Using the Danish medical and pedigree databases, complete tracing of 222 descendants of the original 57 family members was achieved. To date, 10 family members have been diagnosed with CLL, one with T-cell lymphoma and 17 with nonhaematological cancers, including five with breast cancer. The detailed follow up of this family provides further support for inherited predisposition to CLL and illustrates the value of follow-up studies of previously published family material for genetic analyses.

Aged↗
PubMed2000

[Problem-based learning in medical education].

Problem Based Learning (PBL) has not yet been instituted systematically at medical schools in Denmark. We therefore introduced the method in a 10th term course in internal medicine and surgery, eighteen months before graduation, and evaluated the experience after two terms with a total of 93 students and 15 tutors. Compared with traditional education such as bed-side clinics and lectures etc., PBL was the preferred method by 67% of the students, while 28% found the methods equally good and only 2% discredited PBL. The main advantage of PBL was ascribed to motivation and activation, the students finding themselves as being part of the problem-solving situation. The tutors estimated PBL highly when teaching clinical coping strategies, stressing the need for a realistic and appropriate setting. This experience supports the decision to introduce PBL throughout the new medical curriculum in Copenhagen.

Curriculum↗
PubMed2000

[Pseudolymphoma and ventricular maltoma in patients with chronic gastritis, ulcer and Helicobacter pylori infection].

Among 128 patients with malignant B-lymphoproliferative disorders, 19 patients had long lasting dyspepsia and gastroscopy showed chronic active gastritis or gastric ulcer. PCR analysis for TCR and IgH clonality in biopsies showed local involvement of the malignant lymphocyte clone in four patients out of eight indicating presence of these cells in the inflammatory infiltrate. Weak B-cell clonality was found in four patients. A close relationship was seen between lymphocytic clonality and immune response to H. pylori Cag A, and all patients had parietal cell antibodies. Thus, the malignant clone may participate in the local inflammatory reaction, and continued local stimulation by H. pylori as well as parietal cell antigens may lead both to autoimmunity as well as a clonal development of lymphocytes.

Aged↗
PubMed2000

Emerging concepts in the management of the malignant haematological disorders.

A comprehensive review of novel cytoreductive agents is presented. Such novel agents may be found among chemical compounds directed against specific molecular targets (cytostatics) or within the biological substances selectively aimed at the malignant clone (immunotherapy). It is stated that the purposes of immunotherapy in general are to generate a T-lymphocytic response against the tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system of the tumour-bearing host by DNA and/or RNA manipulation with subsequent interference with the signalling pathway in the tumour cells. Some immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene replacement therapy, suicide gene therapy, antisense oligonucleotides, alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most likely, a sequence of different treatment modalities will be used in the future comprising an initial debulking by means of standard chemotherapy and/or irradiation followed by target unspecific immunotherapy (polyclonal immunoglobulins, GvL effect etc.) and finally target specific elimination of residual tumour, probably with repeated use of the minimum effective pharmacologic dose (MEPD) of the agents used. In contrast, the current use of high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD) and associated severe organ toxicity, and high rates of secondary malignancies will probably be substituted in the future. An effective supportive treatment will be highly necessary, especially related to prevention and treatment of infections.

Antibodies, Monoclonal↗
PubMed1999

Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.

OBJECTIVE: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations. SUBJECTS AND DESIGN: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma. SETTING: A university hospital and The State Serum Institute in Copenhagen. INTERVENTION: Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non-infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M-components and monoclonal B-cell proliferation. MAIN OUTCOME MEASURES: Clinical and/or serological autoimmune manifestations, M-component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas. RESULTS: In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti-SSA and -SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations. CONCLUSIONS: To our knowledge this is the first systematic review of B-lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.

Aged↗
PubMed1999

Pharmacoeconomic considerations in treating patients with acute leukaemia.

Whereas individual cost-effectiveness analyses of new agents for acute leukaemia should be performed in target populations, any meaningful pharmacoeconomic evaluation of treatment options for this condition should include the many types of costs and outcomes in unselected, representative groups of patients. Both direct costs (e.g. costs for medication and hospitalisation) and indirect costs (e.g. lost productivity costs and reduced quality of life) are important parameters to assess, as are the costs of chronic adverse effects, research and development costs for new agents, and costs of procedure-related deaths. Complete remission, cure and survival are the 'success' response criteria for acute leukaemia treatments, in addition to prolonged life with acceptable quality of life for patients with incurable acute leukaemia. Death is 'failure', caused either by resistant disease (relapse and progressive disease) inspite of optimal chemotherapy or, sometimes, by insufficient treatment. All of these parameters should be taken into account when a pharmacoeconomic evaluation is performed (either for administrative or scientific purposes) in order to ensure a comprehensive and reliable background for the evaluation in question. Treatment of acute leukaemia is expensive with a total cost of about $US3000 per patient per day during the induction. Although 80% of children with acute leukaemia are cured, only less than 50% of adults are cured. Thus, a great cost is associated with death during treatment and only optimal medical treatment with full-scale combination chemotherapy and full supportive treatment can keep the number of deaths to a minimum.

Acute Disease↗
PubMed1999

Autoimmunity in Waldenström's macroglobulinaemia.

Fifty-seven consecutive patients with Waldenström's Macroglobuliemia were studied retrospectively for autoimmune manifestations. 28 patients or 51% (16 women and 13 men) had clinical and/or serological autoimmune manifestations, two or more of these being concomitant in 20 (12 women and 8 men). The predominant findings were Coombs' positive autoimmune hemolytic anemia (16%), seropositive rheumatoid arthritis (16%), inflammatory gastric ulcer with parietal cell autoantibodies (12%), and IgM-cardiolipin syndrome (11%). 40% of the autoimmune manifestations were present at the time of diagnosis of the Waldenström's Macroglobulinaemia and 60% were observed over a mean period of 4.7 years. All patients had an IgM M-component. There was no correlation between autoimmunity and the size of the M-component or the degree of hypo-IgG and hypo-IgA gammaglobulinemia. The only correlation between autoimmunity and infection was found in patients with gastric ulcer and parietal cell autoantibodies, in whom the infection was caused by Helicobacter pylori.

Aged↗
PubMed1998

Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis.

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.

Aged↗
PubMed1997

Subcutaneous lesions and bacteraemia due to Stenotrophomonas maltophilia in three leukaemic patients with neutropenia.

Subcutaneous lesions were seen in three of 13 neutropenia patients who had Stenotrophomonas (Xanthomonas) maltophilia bacteraemia. The characteristic clinical presentation resembled leukaemic infiltrates, and were different from deep ulcers or subcutaneous nodules caused by Pseudomonas aeruginosa. The three patients had acute leukaemia and were treated with intensive combination chemotherapy. All had previously been treated with broad-spectrum antibiotics, and each patient recovered after proper combination antibiotic treatment given according to sensitivity testing.

Adult↗
PubMed1996

Multiple autoimmune manifestations in monoclonal gammopathy of undetermined significance and chronic lymphocytic leukemia.

In 18 cases of monoclonal gammopathy of undetermined significance, MGUS (monoclonal gammopathy of undetermined significance), admitted for diagnosed or suspected peripheral neuropathy, 11 patients showed other co-existing autoimmune manifestations. Two had POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-component, and skin symptoms), the others mainly endocrinopathy and polyclonal pseudolymphoma. There were 13 cases of sensorimotor neuropathy, two cases of neuritis, while neuropathy could not be confirmed in three cases. Compared with a retrospective review of autoimmunity in a randomly selected CLL (chronic lymphocytic leukemia) cohort of 115 patients, 13 out of 42 patients with clinical and/or laboratory features of autoimmunity showed co-expression of autoimmune signs, the dominating traits being Coombs positive AIHA (auto-immune hemolytic anemia), platelet autoantibodies, endocrinopathy mainly associated with the thyroid gland, serological and/or rheumatological symptoms, but only one case of sensorimotor neuropathy. Viewed from a current model of acquired autoimmunity it is perhaps not surprising that such autoimmunity is seen predominantly in patients with monoclonal gammopathy. Thus, a high concentration of cross-reacting polyreactive autoantibodies related to the M-component might be present in these patients. Furthermore, quantitative defects of the immunoglobulins including the hypogammaglobulinemia associated with M-components can presumably give rise to a defect of the anti-idiotypic network's regulation of natural autoantibodies and autoimmune manifestations in vivo. Such autoimmune manifestations, which are easily overlooked in CLL may call for additional treatment with immunosuppression and/or intravenous, polyclonal IgG.

Adult↗
PubMed1995

Reversal of 'refractory septic shock' by infusion of amrinone and angiotensin II in an anthracycline-treated patient.

A 53-year-old granulocytopenic woman with malignant lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, including doxorubicin (Adriamycin) and autologues bone marrow transplantation, presented in the clinical state of "refractory septic shock" caused by Escherichia coli. Despite inotropic treatment with dopamine, dobutamine, and norepinephrine infusion, the patient's condition did not improve, but during treatment with amrinone and angiotensin II infusion, the septic shock was reversed. The patient was monitored with a pulmonary artery catheter and underwent repeated echocardiographic examinations. Antibiotic treatment with thienamycin and floxacillin was given. The initial reduction in cardiac performance in this patient may be explained by a state of true down-regulation of the myocardial beta-receptors. Apparently these beta-receptors were bypassed via the enzymatic action of amrinone upon cyclic monoadenosine phosphate. This is, to our knowledge, the first doxorubicin-treated patient with septic shock refractory to conventional vasopressor therapy whose condition reversed by inotropic treatment with amrinone and angiotensin II. This treatment may prove to be an alternative choice for patients developing "refractory septic shock" unresponsive to treatment with norepinephrine, dobutamine, and dopamine.

Amrinone↗
PubMed1995

Pharmacoeconomic aspects in the treatment of curable and incurable cancer.

Assessments of the direct and indirect costs of cancer treatment have demonstrated the extreme complexity of these costs. Expenditure on cancer treatment is high, often reaching 3 to 6% of the gross national product in industrialised countries. In this article, we propose that the health outcomes associated with this high expenditure should be analysed in relation to concepts such as total cytoreduction (leading to disease-free survival and cure) and cytostabilisation with acceptable quality of life (in incurable cancer patients). Outcomes appear to be more variable among incurable compared with curable patients, so that cure and survival (which apply to only about 50% of all patients) are not the sole outcome parameters. For the 50% of patients in industrialised countries in whom cure is not possible, outcomes (in the form of cytostabilisation and an ongoing obligation to seek curative cytoreduction) will require further pharmacoeconomic assessment.

Antineoplastic Agents↗
PubMed1994

Changing etiology of bacteremia in patients with hematological malignancies in Denmark.

To ascertain whether the microbiological etiology of bacteremia among patients with hematological malignancies has changed in Denmark, the species distribution of clinically relevant blood culture isolates from the Hematological Department at Rigshospitalet, Copenhagen in 1990 was compared with 2 previous studies (1970-72; 1981-85). In addition, time trends of the etiology of bacteremia among hematological patients in Copenhagen (eastern Denmark) and in Arhus (western Denmark) were compared. In contrast to many other studies, a significant increase in the proportion of Gram-negative aerobes was observed in Copenhagen (from 43% in 1981-85 to 55% in 1990; p < 0.05), whereas in Arhus the proportion of Gram-positive aerobes increased steadily during the 1980s (from 34% to 51%; p < 0.05). In Copenhagen, non-hemolytic streptococci and Xanthomonas maltophilia increased significantly and accounted for 10% (p < 0.01) and 5% (p < 0.05) respectively, of all isolates in 1990, whereas Staphylococcus aureus during the 2 decades studied decreased from 25% to 8% (p < 0.001). In both regions, a decrease was observed in the proportion of Pseudomonas aeruginosa which accounted for only about 5% of all isolates in 1990. No changes were observed in the rates of anaerobes and yeasts. Several factors may contribute to the reported differences in the etiology of bacteremia among hematological patients, e.g. criteria used to assign the clinical significance of the isolate, blood culture system used, practice of using indwelling intravenous catheters, different policies with respect to antimicrobial treatment, and the degree of immunosuppression. A local surveillance of blood culture isolates is mandatory if changes in etiology and resistance development are to be detected.

Bacteremia↗