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J Palmblad

Publications and source records attributed to J Palmblad.

At least 19 recordsLinked to original sources
PubMed1992

Effects of ethanol on the chemotactic peptide-induced second messenger generation and superoxide production in polymorphonuclear leukocytes.

The generation of oxygen radicals by polymorphonuclear leukocytes (PMNL) plays a pivotal role for host defense. Since ethanol reduced FMLP- but not PMA-induced superoxide ion (O2-) formation by PMNL, the effects of ethanol on second messenger systems in PMNL were studied. FMLP induced a biphasic rise in cytosolic calcium concentrations, [Ca2+]i. Ethanol treatment abolished the second phase (believed to reflect Ca2+ influx), an effect also observed in PMNL treated with La3+ or suspended in Ca(2+)-free buffer. The FMLP-induced inositol trisphosphate generation was unaffected by ethanol, whereas diacylglycerol formation was, as expected, markedly reduced. Propranolol, an inhibitor of diacylglycerol formation from phosphatidic acid, caused a prolonged transmembrane influx of Ca2+ and partially reversed the inhibitory effect of ethanol on FMLP-induced O2- production. Thus, the ability of ethanol to inhibit FMLP-induced O2- generation in neutrophils seems to be due to both impaired influx of Ca2+ across the plasma membrane and reduced phospholipase D-mediated generation of phosphatidic acid.

Calcium↗
PubMed1992

Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias.

We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden.

We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone.

Adolescent↗
PubMed1992

A pilot study of piperacillin and ciprofloxacin as initial therapy for fever in severely neutropenic leukemia patients.

We studied the efficacy of piperacillin and ciprofloxacin as initial parenteral therapy in 41 adult patients with leukemia who developed 47 febrile episodes during severe neutropenia following chemotherapy. 40 patients (98%) survived their febrile episode(s), whereas 1 patient died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 24/47 episodes (51%) had been successfully treated. These 24 favourable responses were seen in 15/24 (63%) microbiologically documented infections and 9/19 (47%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 46 episodes were evaluable, and 28 (61%) had responded successfully to piperacillin and ciprofloxacin. Successful treatment was most frequently observed in microbiologically defined infections, 18/23 (78%). Three of 5 (60%) Gram-positive, 11/12 (92%) Gram-negative and 1 of 2 mixed bacteremias were successfully treated. In contrast, only 10/19 (53%) FUO and none of 4 clinically defined infections had responded. Thus, this pilot study indicates that piperacillin and ciprofloxacin may be a safe and effective combination for the treatment of febrile episodes in severely neutropenic leukemia patients, which merits further investigation in randomized trials.

Adult↗
PubMed1991

Synthesis, structural identification and biological activity of 11,12-dihydroxyeicosatetraenoic acids formed in human platelets.

An enantiospecific route for the synthesis of 11,12-dihydroxyeicosatetraenoic acids was developed and used to synthesize 11,12-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acids. The 11,12-DHETEs were synthesized with the stereochemistry of the hydroxyl group being 11(R),12(S) and 11(S),12(S). The synthetic compounds were used to elucidate the structure of 11,12-DHETEs formed in human platelets by comparison of the chromatographic retention time in HPLC and GC as well as their ion fragmentation pattern in GC-MS. The major 11,12-DHETE formed in human platelets was found to be identical with 11(R),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid. Two more compounds were tentatively identified as 11(S),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid and 11,12-dihydroxy-5(E),7(E),9(E),14(Z)-eicosatetraenoic acid. Furthermore, the 11(S),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid was found to possess biological activity on neutrophil functional responses. However, the major compound, 11(R),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid, formed in platelets lacks biological activity in the test systems used. The present data further support that 11,12-dihydroxy-eicosatetraenoic acids are formed in human platelets via a leukotriene like mechanism presumably by the 12-lipoxygenase. Furthermore, the biological effects of one of the compounds showed a unique activity profile compared to other lipoxygenase products.

Blood Platelets↗
PubMed1991

Ethanol impairs certain aspects of neutrophil adhesion in vitro: comparisons with inhibition of expression of the CD18 antigen.

Since ethanol impairs polymorphonuclear leukocyte (PMNL) delivery to inflammatory sites, the effect of ethanol on PMNL adhesiveness was studied in vitro. Ethanol inhibited PMNL aggregation induced by formylmethionylleucylphenylalanine (FMLP) but not by phorbol myristate acetate (PMA), whereas responses to both stimuli were abolished by treating PMNL with monoclonal antibody 60.3 (against the adhesion protein CD18). This antibody also abrogated spontaneous and FMLP-stimulated PMNL adhesion to plastic, whereas ethanol reduced spontaneous but not FMLP-induced adherence. Chemotaxis in Boyden or agarose systems was not diminished by ethanol, but high concentrations of MAb 60.3 inhibited migration under agarose. Nonetheless, upregulation of cell surface expression of CD18 (assessed by immunofluorescence flow cytometry) induced by FMLP or PMA was similarly reduced by ethanol. Thus, ethanol inhibited only certain of PMNL adhesion, and although the stimulated up-regulation of CD18 expression was reduced it is unlikely that ethanol effects were mediated only by this inhibition.

Antigens, CD↗
PubMed1991

The effect of 20-trifluoromethyl leukotriene B4 on neutrophil functional responses.

20-trifluoromethyl-leukotriene B4 (20CF3-LTB4) is a stable derivative of leukotriene B4 (LTB4) that is not subjected to omega-oxidation to less active metabolites. 20CF3-LTB4 was as potent as LTB4 as a chemotactic, adhesion-promoting and aggregatory agent for human neutrophils, but had only 11 +/- 3% of the ability to induce an oxidative response. Nonetheless, both compounds were equally efficient in order to confer a rapid and monophasic increment of the concentration of cytosolic calcium. The kinetics of the calcium, aggregatory and chemiluminescent responses to 20CF3-LTB4 were similar to that of LTB4. These findings suggest that the insertion of the trifluoromethyl group into the LTB4 molecule causes a shift of the biological activity profile, suggesting that 20CF3-LTB4 binds mainly to high affinity LTB4 receptors. Moreover, the similarity of the response kinetics of LTB4 and 20CF3-LTB4 suggests that the mechanism for the rapid and transient responses of LTB4 is not due to its omega-oxidation.

Calcium↗
PubMed1991

Effects of an essential fatty acid-supplemented diet on leukotriene B4-induced rat neutrophil functions.

This study evaluated the effect of dietary supplementation with the essential fatty acid linoleic acid to 10% of the energy content of a diet on the stimulus-response coupling of rat peritoneal neutrophils. When stimulated with leukotriene B4 neutrophils from essential fatty acid supplemented rats responded with a significantly more pronounced oxidative metabolism (assessed as luminol augmented chemiluminescence) relative to control cells from rats on a normal 3% of total energy essential fatty acid diet. Chemiluminescence response to the formylpeptide N-formyl-norleucyl-leucyl-phenylalanine-norleucyl-thyrosyl-leucine was similarly enhanced. In contrast, responses elicited by the lectin concanavalin A did not differ between the two dietary groups. In response to leukotriene B4 a dose-related inhibition of neutrophil aggregation was observed, whereas chemotaxis did not differ between the two groups. Thus, linoleate supplementation is associated with a stimulus-specific modulation of neutrophil oxidative and aggregatory responses suggesting an effect on early, conceivably receptor-linked, steps of the stimulus-response coupling.

Animals↗
PubMed1991

Antirheumatic effects of fasting.

Total fasting induces within a few days a substantial reduction of joint pain, swelling, morning stiffness, and other arthritic symptoms in patients with rheumatoid arthritis. This remission subsides slowly after discontinuation of fasting. Its mechanisms are complex and involves diminished activation of neutrophils and lymphocytes and decreased generation of leukotrienes and of concentrations of serum complement factors, as well as of other proinflammatory systems. Moreover, ketosis and other metabolic and endocrine changes may be of significance for symptom expression and recognition.

Arthritis, Rheumatoid↗
PubMed1990

Leukotriene B4 induced hyperadhesiveness of endothelial cells for neutrophils.

Leukotriene B4 (LTB4) induced a transient state of hyperadhesiveness in cultured human umbilical vein endothelial cells (HUVEC), leading to increased binding of neutrophil granulocytes (PMN). The effect of LTB4 was more rapidly emerging and transient than responses to platelet activating factor (PAF), thrombin and phorbol myristate acetate (PMA). At 0.1 microM of LTB4, it was comparable to hyperadhesiveness induced by 1 U/ml of thrombin, but less than that conferred by 0.1 microM of PAF and PMA. The adherence response to LTB4 was specific since the structural analogue 5S,12S-diHETE, which lacks PMN-stimulating effects, failed to promote HUVEC adhesiveness.

Cell Adhesion↗
PubMed1990

Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera.

Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.

Adult↗
PubMed1990

Trimethoprim-sulphamethoxazole-associated blood dyscrasias. Ten years' experience of the Swedish spontaneous reporting system.

During the 10-year period 1976-1985, a total of 154 cases of blood dyscrasia were reported in Sweden which were evaluated as having a probable or possible causal relationship with trimethoprim-sulphamethoxazole (T-SM). There were 61 cases of leucopenia (of which 16 had agranulocytosis), 28 cases of thrombocytopenia, and two of non-haemolytic anaemia. There were also 32 cases of bicytopenia and 31 cases of tricytopenia. The median age varied from 38 years in the leucopenia group to 81 years in those with tricytopenia. The overall fatality rate was 17%, ranging from 2% in the group with mild leucopenia to 52% in the group with tricytopenia. In relation to sales and prescription data, the overall incidence of reported T-SM blood dyscrasias was 5.3 per million defined daily doses, and among out-patients the incidence was one case per 18,000 prescriptions. Thus the overall incidence of any blood reaction to T-SM appears to be low. In relation to prescription data, elderly people were overrepresented among the serious reactions.

Adult↗
PubMed1990

Treatment of drug-induced agranulocytosis with recombinant GM-CSF.

A 53-year male patient, treated for rheumatoid arthritis with sulphasalazine, developed a total agranulocytosis. When this state had prevailed for at least 10 d no bone marrow granulocyte progenitor cells were detectable. Intravenous GM-CSF treatment was initiated 5 d later, and the patient recovered within the next 6 d. GM-CSF treatment for severe agranulocytosis deserves further investigation.

Agranulocytosis↗
PubMed1990

Rapid adhesive responses of endothelial cells and of neutrophils induced by leukotriene B4 are mediated by leucocytic adhesion protein CD18.

Controversy has existed as to the ability of leukotriene B4 (LTB4) to enhance adhesive properties of human neutrophils (PMN) and endothelial cells. We found that LTB4 induced a rapid but transient adhesion of PMN to an albumin-coated plastic surface and to cultured human umbilical vein endothelial cells (HUVEC). Although the adhesive response of PMN to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was longer lasting, peak hyperadherence was of similar magnitude as to LTB4 and was less susceptible to assay conditions. Adherence induced by either LTB4 or fMLP could be abrogated by the monoclonal antibody 60.3, indicating similar dependence on the leucocyte adhesion protein CD18. Lipoxin A did not induce PMN hyperadherence. Treating HUVEC with LTB4, but not with its omega-oxidized metabolites 20-OH- and 20-COOH-LTB4, lipoxin A, or with fMLP conferred a rapid, dose-related, enhanced adhesion of PMN. This effect was dependent on CD18 and on divalent cations. It disappeared with prolonged exposure to LTB4, required a metabolically active HUVEC, and was not due to passive binding of LTB4 to HUVEC. Thus, LTB4 induces a transient expression of hyperadhesiveness in HUVEC as well as in neutrophils, and both effects are dependent on expression of CD18.

Antibodies, Monoclonal↗