Biomedical subjects
R Lahtinen
Publications and source records attributed to R Lahtinen.
Phospholipases A2 in the reproductive system of the bull.
1. Phospholipase A2 activities were studied in the reproductive organs, seminal plasma and spermatozoa of adult bulls. 2. Phosphatidylethanolamine and phosphatidylcholine with 14C-labelled linoleic (lino-PE, lino-PC) or arachidonic acid (ara-PE, ara-PC) at sn-2 position as well as a fluorescent derivative (4-pyrenylbutyric acid) of phosphatidylcholine (PPC) were used as substrates. 3. The radioactive substrates were hydrolysed most strongly by homogenates of the prostate and Cowper's gland, but also seminal vesicle and its secretory fluid, seminal plasma and ejaculated spermatozoa contained hydrolytic activity. The fluorescence substrate was most strongly hydrolysed by homogenates of ampulla and seminal vesicle as well as its secretory fluid, seminal plasma and ejaculated spermatozoa. 4. Seminal plasma and seminal vesicle fluid contained a Ca2(+)-independent enzyme (enzyme I), which hydrolysed only PPC, while another Ca2(+)-dependent enzyme (enzyme II) hydrolysed only the radioactive substrates. 5. Both enzymes were purified from the seminal vesicle fluid and their biochemical properties were analysed. In SDS-PAGE enzyme I preparation resulted in two major bands with molecular weights of 16,000 and 60,000 in equal quantities and minor band at 15,000. The binding of the enzyme I to Con A-Sepharose indicated that it is a glycoprotein and it had multiple pI-values from 3.75 to 5.0. Enzyme II gave in SDS-PAGE two closely located bands with molecular weights of about 15,000 and 16,000 (major band). Isoelectric focusing showed one band at pI 4.7. Both enzymes appear to bind to spermatozoa at ejaculation but their function remains to be shown.
Cardiotoxicity of epirubicin and doxorubicin: a double-blind randomized study.
24 patients with non-Hodgkin lymphoma were randomized into two multidrug regimens including either epirubicin (N = 12) or doxorubicin (N = 12) to establish the cardiotoxicity of each treatment modality. At cumulative doses of 400-500 mg/m2 left ventricular ejection fraction (LVEF) at rest determined by radionuclide angiocardiography decreased significantly more in the doxorubicin (-15 +/- 11%) than in the epirubicin group (0 +/- 13%, p less than 0.005). During epirubicin therapy no clinically significant cardiotoxicity developed, but a decrease larger than 10% in LVEF was seen in 4 of 12 patients at a mean cumulative level of 450 mg/m2. During doxorubicin therapy 1 patient developed a heart failure at a cumulative level of 200 mg/m2 and, altogether, in 7 patients LVEF decreased more than 10%. The monitoring of cardiac toxicity is imperative in patients treated with doxorubicin and is advisable if the patient is expected to receive epirubicin at more than 450 mg/m2.
Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia.
108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.
Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin.
10 subjects with Hb Linköping (beta 36 Pro greater than Thr), a high-affinity hemoglobin variant, with a P50 of 2.2 kPa (16.5 mm Hg) were investigated before and 3-4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 +/- 13 (SD) to 146 +/- 15 g l-1 and the red cell volume from 2.77 +/- 0.83 to 2.23 +/- 0.67 l. Maximal oxygen consumption decreased slightly by 2.7 +/- 3.8 ml min-1 kg-1 and maximal exercise power by 11 +/- 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (-1.1 +/- 6.4 beats min-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 +/- 10.3 ml min-1 100 g-1 from before to after hemodilution. The results indicate that subjects with Hb Linköping have only limited benefit from their increased blood hemoglobin concentration.
[Aspergillus infections in patients suffering from malignant blood diseases].
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[Osteolytic bone lesions, hypercalcemia and malignant lymphoma].
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Hydrolases from bovine seminal vesicle, prostate and Cowper's gland.
The bovine seminal plasma is formed mainly by secretions of epididymis and the glandular epithelia in ampulla, seminal vesicles, prostate and Cowper's glands. The contribution of each organ to the hydrolytic enzyme activities (glycosidases, exopeptidases, phospholipases) of the bull seminal plasma has been analyzed and is reviewed in this paper with special emphasis on the role of the accessory glands. Seminal vesicles seem to have a major role in the secretion of seminal plasma acid alpha-glucosidase, acid alpha-mannosidase and beta-N-acetylhexosaminidase, aminopeptidase A, dipeptidyl peptidase II and IV and gamma-glutamyl transpeptidase as well as Ca(2+)-dependent and Ca(2+)-independent phospholipases A2 with distinct substrate specificities, a choline-specific phospholipase C and a Co2+ (Mn2+)-activated sphingomyelinase. The enzyme pattern in the ampulla closely resembled that of the seminal vesicles and obviously contributes to the seminal plasma level of these hydrolases. The bull prostate and Cowper's glands contained a strong Ca(2+)-dependent phospholipase A2 activity. However, these glands may not contribute to the seminal plasma PLA2 activity. At ejaculation the epididymal spermatozoa are exposed to these enzymes. They may have a specific affinity to sugar, peptide or phospholipid residues at distinct sites of the sperm surface. These enzymes may also participate in the digestion of various other semen components to create a suitable milieu for the emitted spermatozoa.
Acute febrile neutrophilic dermatosis (Sweet's syndrome) in association with myelodysplastic syndromes: a report of three cases and a review of the literature.
Three patients with acute febrile neutrophilic dermatosis (AFND, Sweet's syndrome) in association with myelodysplastic syndromes (MDS) are described and, in addition, another 10 published cases are reviewed. In the reviewed patients the male/female ratio is 2:1. The great majority of the patients had decreased or normal leucocyte counts at the time the syndrome developed. Chromosome analysis was available in eight cases: in three the karyotype was normal while five patients had a clonal abnormality. No clinical or laboratory parameters seemed to predict the response to steroids: all but one of the treated patients responded promptly. Moreover, three patients recovered spontaneously. Shortly after the appearance of Sweet's syndrome nine patients developed acute leukaemia and one patient died with hypoplasia. Development of Sweet's syndrome in association with MDS may not be an uncommon clinical finding. The occasional MDS patient developing AFND will often progress into acute leukaemia and thus the occurrence of AFND warrants a bone marrow examination and close follow-up of the patient.
Discordance in the development of peripheral and autonomic neuropathy during vincristine therapy.
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[Management of Hodgkin's disease].
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Monosomy 7 predisposes to diabetes insipidus in leukaemia and myelodysplastic syndrome.
We studied the chromosomes in the bone marrow of 4 patients who had both diabetes insipidus (DI) and acute non-lymphocytic leukaemia. Clinical findings suggested that, in each case, myelodysplastic syndrome had preceded the onset of acute leukaemia. Two other such patients described in the literature had had a banded karyotype study of bone marrow cells. All 6 patients had deletions of chromosome 7. 3 had monosomy 7 as the sole cytogenetic abnormality, 2 had monosomy 7 associated with other clonal abnormalities and 1 had del(7)(q22) in association with other abnormalities. These data suggest that monosomy 7 or perhaps monosomy for 7q22-qter predisposes to DI. The mechanism by which the proposed predisposition is produced remains to be clarified.
Molecular characterization of chromosome 7 long arm deletions in myeloid disorders.
Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions. No molecular abnormalities occurred in lymphocyte-derived DNA. Several probes located in band 7q22 or distally thereof detected deletion of one allele in granulocyte-derived DNA from all four patients with chromosome 7 long arm deletion. In the granulocytes of one patient heterozygosity for the T cell receptor beta chain gene (in band 7q35) indicated that the deletion was interstitial. NJ-3, a proalpha2(I)collagen gene probe (in band 7q21-22) detected heterozygosity in the granulocytes of one patient. No hemizygosity or deletions were found in four patients with two normal chromosomes 7. These results confirm that mature granulocytes but not lymphocytes are derived from the abnormal clone. Interstitial deletions exist, and the extent of deleted genomic material varies among patients.
Exercise capacity in subjects with high oxygen affinity.
Exercise capacity and hemodynamic parameters were measured in ten patients with a previously unpublished variant of hemoglobin (Hb-Linköping) and in ten age- and sex-matched controls. Bicycle ergometer test was almost maximal and the indices of working capacity and cardiac tolerance were similar in patients and controls. The hemoglobin dissociation curve was shifted to the left at rest and after exercise the shift to right was half of the corresponding shift in controls. Lactate accumulation during exercise was similar in patients and controls, also the elimination rate seems identical, but requires further studies. Hydrogen ion production in the patients during exercise was more marked than in the controls. If this is a sign of altered energy metabolism remains to be ascertained in future studies. In acute short-term exercise the patients with abnormally high hemoglobin oxygen affinity seem to have similar tolerance and cardiovascular load. Aberrant metabolism and adaptation to relative hypoxia in spite of erythrocytosis may have long-term effects that require long-term follow-up of these patients.
[Hemoglobin Linköping and physical performance].
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[Busulfan and eye complications].
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Diabetes insipidus in preleukaemic phase of acute myeloid leukaemia in 2 patients with empty sella turcica. A report of 2 cases.
2 patients with diabetes insipidus established in the preleukaemic phase of acute myeloid leukaemia are described. Both patients had probably coincidentally an empty sella turcica showed by a computerized tomography. In one of them, leukaemia developed secondary to a cytostatic therapy for a vesical cancer. In this patient, blast cells appeared in cerebrospinal fluid after the patients had become polyuric and later on autopsy findings showed a peripituitary leukaemic infiltrate. In the other patient, diabetes insipidus and the acute phase of leukaemia developed after a long period with a dysmyelopoietic syndrome. Hormonal tests suggested a hypothalamic injury in both patients due to a leukaemic infiltrate at least in the former of them. It is concluded that diabetes insipidus as a consequence of hypothalamic lesion may develop in the preleukaemic phase of acute myeloid leukaemia and become evident before any other symptoms of leukaemia have manifested.