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Biomedical subjects

T Pettersson

Publications and source records attributed to T Pettersson.

At least 55 records · Page 3Linked to original sources

Urinary alpha 1- and beta 2-microglobulin in light chain proteinuria.

Thirteen patients with light chain (LC) proteinuria (11 with multiple myeloma and two with monoclonal gammopathy of undetermined significance) were followed up for one to 3.5 (median 2.5) years and studied for urinary excretion of LCs, alpha 1-microglobulin (alpha 1 M), beta 2-microglobulin (beta 2M), albumin, and serum creatinine concentration at intervals of 6 +/- 2 months. At the beginning of the follow-up, urinary alpha 1M excretion correlated with that of beta 2M (r = 0.81, p = 0.0007) and LCs (0.69, p = 0.0084), and with the serum creatinine level (r = 0.56, p = 0.047). During the follow-up period, renal function remained stable in eight patients despite high or fluctuating LC excretion. In seven of them, urinary alpha 1M was repeatedly below 150 mg/24 h and in one it transiently exceeded that level. The remaining five patients had an unstable renal function (deterioration in four, improvement in one) although their urinary LC and albumin excretion during the study period was comparable to those in patients with stable renal function. In the five patients with unstable renal function, high (> 150 mg/24 h) urinary alpha 1M excretion was associated with a rise in the serum creatinine level. alpha 1M excretion was thus found to be a useful indicator of renal damage caused by LCs.

Aged↗

[Troponin T in acute myocardial infarction. Diagnosis and prognosis in patients admitted for suspected acute myocardial infarction].

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients who on admission were suspected of acute myocardial infarction (AMI) to the coronary care units of six Scandinavian hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator value of TnT of 0.20 micrograms/l. One hundred and fifty-five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values > or = 0.20 micrograms/l); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values < 0.20 micrograms/l). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values > or = 0.20 micrograms/l, and a group of 83 patients with TnT below this level. A follow-up study was able to define the clinical significance of these findings. The cumulative six months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI. We conclude that increased troponin T in serum can detect a subgroup of IHD-patients in whom AMI has been ruled out, but who still have a prognosis as serious as that of patients with definite AMI.

Adult↗

Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid arthritis.

The effect of recombinant human erythropoietin (rHuEPO) on haem biosynthesis in peripheral red blood cells was evaluated in 12 patients with RA and anaemia (mean haemoglobin concentration 102 g/l, range 90-109 g/l). Before treatment, the serum concentrations of erythropoietin (EPO) were low (mean 13 pmol/l, range 5-32 pmol/l), the activities of haem-synthesizing enzymes within the reference intervals and the erythrocyte protoporphyrin (E-PROTO) concentrations clearly higher than normal. Nine patients responded with an increase in the haemoglobin level of 15 g/l or more. rHuEPO induced a rise in the mean haem synthase (HAEM-S) activity from a baseline of 12.1 to a maximum of 26.8 pmol/h per 10(6) reticulocytes after 20 weeks of treatment (P < 0.002). The mean E-PROTO concentration also rose and reached its maximum at 8 weeks of treatment. We conclude that correction of anaemia in patients with RA using rHuEPO is associated with an activation of HAEM-S, commonly regarded as the rate-limiting enzyme of haem synthesis in erythroid cells. Functional iron deficiency probably explains the simultaneous rise in E-PROTO concentration.

Adult↗

Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases?

We investigated whether determination of serum transferrin receptor (TfR) is useful for detecting iron-deficiency in patients with chronic inflammatory diseases and for differentiating between iron-deficiency anaemia and anaemia of inflammation. Using an immunofluorometric assay, serum TfR was measured in 34 anaemic patients. Of these patients, 23 had a chronic rheumatic disease, 13 with both inflammation and iron-deficiency and 10 with anaemia of inflammation only; the other 11 patients had iron-deficiency anaemia and no evidence of inflammation. Serum TfR concentrations were lower in patients with anaemia of inflammation (2.6 +/- 0.2 mg/l, mean +/- S.E.M.) than in patients with iron-deficiency anaemia (6.7 +/- 1.1 mg/l, P < 0.01) or those with both inflammation and iron deficiency (5.8 +/- 1.0 mg/l, P < 0.01). Among patients with inflammatory disease, correlations between TfR and ferritin concentrations (r = -0.62, P < 0.05) and TfR and erythropoietin concentrations (r = 0.69, P < 0.001) were observed in iron-deficient subjects only. TfR, though not superior to serum ferritin, can help to distinguish between anaemia of inflammation and iron-deficiency anaemia and to identify iron-deficiency in subjects with chronic inflammation.

Adult↗

Lineage involvement and karyotype in a patient with myelodysplasia and blood basophilia.

We report a 63-year-old woman with myelodysplastic syndrome (MDS), refractory anaemia with ring sideroblasts (RARS), and blood basophilia with pathological forms. Karyotype analysis revealed a complex rearrangement: 46,XX,del(3)(p13p25),del(5)(q13q33),der(16)t(1;16) (p13;q12)/47,idem,add(20)(?p11)/49,idem, + add(1)(q32),add(20)(?p11), + mar/46,XX. Karyotype, immunophenotype and in situ hybridization studies by the MAC (morphology antibody chromosomes) combination technique revealed the chromosomal abnormality in granulocytic/monocytic and erythrocytic metaphase cells. Also mature basophils and other granulocytes were involved with the abnormality. We suggest that our patient with the MDS has a stem cell disorder affecting all myeloid cell lineages and that basophilia constitutes a part of the malignant process.

Basophils↗

Pleural fluid soluble interleukin 2 receptor in rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To study local cellular immune reactions in the pleural fluid of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Using an immunoenzymometric assay, the concentration of soluble interleukin 2 receptor (sIL-2R) was measured in the pleural fluid of 13 patients with RA, 6 patients with SLE and 72 patients with pleural effusions of other etiologies, including tuberculosis, cancer, pneumonia and congestive heart failure. RESULTS: The mean pleural fluid sIL-2R concentration was significantly higher in patients with RA (593 pM, range 252-1558) than in patients with SLE (145 pM, range 94-236; p < 0.005), cancer (224 pM, range 98-521, p < 0.01), pneumonia (177 pM, range 60-343, p < 0.005) and congestive heart failure (139 pM, range 56-228, p < 0.005), but as high in patients with tuberculous pleurisy (mean 390 pM, range 151-512). The highest mean pleural fluid to serum sIL-2R ratios were observed in patients with RA and with tuberculosis. CONCLUSION: Measurement of sIL-2R in pleural fluid is useful for the differentiation of pleural effusions in RA from those occurring in SLE. High levels of sIL-2R associated with a local T cell mediated immune reaction may serve an immunoregulatory purpose in rheumatoid pleurisy.

Adolescent↗

Non-dysplastic myelodysplasia?

Patients successfully treated for a malignancy with cytotoxic therapy have an increased risk of developing secondary myelodysplasia (MDS) and acute myeloid leukemia (AML). We report a patient in remission from Hodgkin's disease (HD) who remains hematologically normal 4 years after combination chemotherapy, but who has biological and genetic abnormalities characteristic of myelodysplasia. X-inactivation analysis using a 5' phosphoglycerate kinase (PGK) probe demonstrates polyclonal hematopoiesis, but cytogenetic analysis reveals a clonal population with a minority of metaphases having a 7q-deletion. NRAS mutations are not detectable 1 year after treatment, but are present in two separate clones (at codons 12 and 15) analyzed by single-stranded conformational polymorphism (SSCP), followed by cloning and sequencing 4 years after treatment. The presence of an activated NRAS with the same codon 12 mutation was independently confirmed by the nude mouse tumorigenicity assay. In vitro peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) have changed from normal to undetectable levels while erythroid burst forming units (BFU-E) were significantly reduced on two occasions during the period of observation. These abnormalities are characteristic of MDS. Continued clinical follow-up will determine whether these evolving genetic and biological abnormalities pre-date the onset of clinical and morphological features of MDS.

Adult↗

Rheumatoid arthritis as a cause of cardiac compression. Favourable long-term outcome of pericardiectomy.

In order to clarify the significance of rheumatoid arthritis (RA) as a cause of cardiac compression, we scrutinized pericardiectomy files of 47 patients over a ten-year period at two university hospitals in Finland. Five patients with RA were found. All the patients with RA were men with seropositive disease and subcutaneous rheumatoid nodules. Two of the patients had pulmonary fibrosis, one had cutaneous vasculitis and three had had rheumatoid pleurisy. There was a mean delay of 10 months from the first cardiac symptom to the diagnosis of cardiac compression, the most common misdiagnosis being primarily a liver disease. On the basis of clinical and operative data, four out of the five patients had constrictive pericarditis and one had an effusive-constrictive form of the disease. The histopathological findings in all cases were consistent with chronic fibrosing pericarditis. A follow-up of seven to seventeen years of four patients has not revealed any signs of recurrent pericardial disease. Our results demonstrate that RA is an important aetiological factor for cardiac compression. The long-term outcome of this manifestation seems to be good after pericardiectomy.

Adult↗

High concentrations of eosinophil cationic protein and eosinophil protein X in eosinophilic pleural effusions.

To analyze the association of the eosinophil granulocyte with pleural effusions, we measured the concentrations of two eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), in pleural fluid and serum of 92 patients with pleural effusions of various causes. We observed significantly higher ECP and EPX concentrations in eosinophilic than in noneosinophilic pleural effusions (p < 0.001 and p < 0.05, respectively) and a positive correlation between the concentrations of both eosinophil proteins in pleural fluid and the total number of eosinophils in pleural fluid (ECP: r = 0.66, p < 0.0001; and EPX: r = 0.62, p < 0.0001). There was a positive correlation between the concentrations of ECP in pleural fluid and serum (r = 0.74, p < 0.0001) and between the concentrations of EPX in pleural fluid and serum (r = 0.41, p < 0.001). High ECP and EPX concentrations in pleural fluid indicated nonspecific etiology and not tuberculosis as the cause of the effusion. Our results suggest that eosinophils in pleural effusions release eosinophil proteins and probably actively participate in the local inflammatory reaction.

Blood Proteins↗

Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction.

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients suspected of having acute myocardial infarction (AMI), and admitted to the coronary care units of six Scandinavian Hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator TnT value of 0.20 microgram l-1. One hundred and fifty five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values of > or = 0.20 micrograms l-1); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values of < 0.20 microgram l-1). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values of > or = 0.20 microgram l-1, and a group of 83 patients with TnT below this level. An equal identification of these patients among the centres was seen (mean +/- SD 35 +/- 13%; range 20-55%). A follow-up study was able to define the clinical significance of these findings. The cumulative 6 months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin. Slower response in patients with more severe inflammation.

We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.

Adult↗

Production, purification and characterization of recombinant human interferon gamma.

An essentially three-step chromatographic purification procedure, i.e., ion-exchange, immobilized metal ion affinity and size-exclusion chromatography, is described for the purification to homogeneity of recombinant human interferon-gamma (rhIFN-gamma) from the inclusion bodies produced in genetically transformed Escherichia coli cells. Batchwise adsorption of the cloudy solution of renatured rhIFN-gamma obviated the need for high-speed centrifugation to clarify the suspension. This step effectively removed about 70% of extraneous protein impurities. The established purification process is reproducible and leads to a total recovery of 32%. Pilot-scale processing of E. coli cells grown in a 30-l fermentor gave about 70 mg of a homogeneous preparation of rhIFN-gamma. The specific biological activity of purified rhIFN-gamma is ca. 3.4 x 10(7) I.U./mg protein, which is comparable to that of its natural counterpart. It is basic protein (pI greater than pH 9) with a monomer relative molecular mass of 15,000. It behaves, however, as a dimer on size-exclusion chromatography. Its partial NH2-terminal sequence is identical with that established for the rhIFN-gamma. However, its amino acid composition and its relative molecular mass (15,067 as determined by electrospray mass spectrometry) indicate that the purified protein is a truncated form lacking fifteen amino acid residues from its carboxyl-terminal side. This modification does not seem to have any adverse effect on its biological potency. The levels of DNA, bacterial endotoxins and Ni(II) ions in the final product were determined.

Amino Acid Sequence↗

Granzyme A-immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis.

Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A-immunoreactive cells formed 8 +/- 2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29 +/- 4% (p < 0.05 compared to normal peripheral blood) and 25 +/- 4% (p < 0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A-positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis.

Adult↗

Increased CKMB (mass concentration) in patients without traditional evidence of acute myocardial infarction. A risk indicator of coronary death.

A study of 102 patients consecutively admitted to a coronary care unit (CCU) investigated the clinical usefulness of three different immunoenzymometrical CKMB methods: NovoClone CK-MB, ICON QSR CKMB and IMx CK-MB. Blood samples were drawn on admission and then every 6 h for 48 h. The three different methods correlated very well (r = 0.93-0.96). With discrimination levels of 10 micrograms.l-1 for NovoClone CK-MB and 5 micrograms.l-1 for the other two methods, a sensitivity of 1.0 and a still acceptable specificity (> 0.81) were achieved. In the group of patients (n = 53) with suspicion of acute myocardial infarction (AMI) but with no standard criteria for AMI, 14 patients were identified with small but significant increase of serum CKMB (mass concentration) and an increased CKMB (mass concentration)/CK ratio. During a 4 year follow-up nine out of these 14 patients died within 2 years, the majority being coronary deaths, as compared to only two out of the remaining 39 non-AMI patients with suspicion of AMI but with normal CKMB values (chi 2 = 18.47, P < 0.001). The finding of such a high mortality rate among patients with increased CKMB (mass concentration) has an important prognostic value even in patients without standard criteria for AMI.

Adult↗

Cytophagic histiocytic panniculitis: a report of four cases.

Four patients presented with a clinical picture of spiking fever, erythematous nodular subcutaneous skin lesions, anaemia and leucopenia. Inconstant features were weight loss (3/4), splenomegaly (3/4), thrombocytopenia (3/4), raised liver enzymes (3/4), hepatomegaly (2/4) and serosal effusions (2/4). The histopathological findings of lobular histiocytic panniculitis with 'bean-bag' cells were characteristic of cytophagic histiocytic panniculitis (CHP). No infectious agent could be detected, and there was no histological evidence of malignant neoplasia. Unlike most previously described patients with CHP, three of our four patients responded to treatment with immunosuppressive or cytostatic drugs.

Adipose Tissue↗

Autosomal dominant 'Mediterranean fever' in a Finnish family.

A 23-year-old Finnish man was examined because of an 8-year history of recurrent bouts of fever and abdominal pain. His father had been repeatedly investigated because of similar episodes since he was 24 years old, and one of the father's sisters was reported to have had recurrent periods of fever. The clinical features closely resembled those of familial Mediterranean fever (FMF), a syndrome rarely described in families of European descent. Unlike typical FMF, which is inherited as an autosomal recessive trait, the mode of inheritance of the syndrome in our family may be regarded as dominant. During a recent attack, serum concentrations of interleukin-1-beta, interleukin-6 and acute phase reactants, including serum amyloid A protein, were high. No signs of amyloidosis were detected in our patients.

Adult↗