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1.
J Intern Med ; 290(5): 1048-1060, 2021 11.
Article in English | MEDLINE | ID: mdl-34003533

ABSTRACT

BACKGROUND: The outcome for diffuse large B-cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R-CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. METHOD: We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma-free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population-based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. RESULTS: Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14-1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10-2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01-1.64). Among younger patients (≤70), a short-term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30-day survival among patients and comparators. CONCLUSION: DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Myocardial Infarction , Cohort Studies , Female , Humans , Incidence , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/epidemiology , Male , Myocardial Infarction/epidemiology , Risk Factors , Sweden/epidemiology
2.
Haematologica ; 101(12): 1573-1580, 2016 12.
Article in English | MEDLINE | ID: mdl-27198718

ABSTRACT

Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adenine/analogs & derivatives , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Chromosome Aberrations , Compassionate Use Trials , Disease Progression , Drug Resistance, Neoplasm , Female , Humans , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Neoplasm Staging , Piperidines , Proportional Hazards Models , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Recurrence , Retreatment , Retrospective Studies , Sweden , Treatment Outcome
3.
Scand J Immunol ; 79(6): 415-22, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24684541

ABSTRACT

Antigen-loaded dendritic cells (DCs) used as anticancer vaccine holds promise for therapy, but needs to be optimized. The most frequently described DC vaccine is being matured with a cocktail containing prostaglandin E2 (PGE2 DC). However, even though PGE2 DCs express both costimulatory and migratory receptors, their IL-12p70-prodcution is low, leading to an insufficient Th1 immune response. As an alternative, α-type-1 polarized DCs (αDC1s) have shown a superior production of IL-12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia (CLL) patients, αDC1s can be generated to induce a functional Th1-immune response. Yet, another costimulatory receptor, CD70, appears to be essential for optimal DC function by promotion of T cell survival and function. So far, PGE2 is suggested as one of the most important factors for the induction of CD70 expression on DCs. Therefore, we wanted to investigate whether αDC1s have the ability to express functional CD70. We found that CD70 expression on αDC1s could be upregulated in the same manner as PGE2 DCs. In an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70 on αDC1s from controls reduced effector cell proliferation although this could not be found when using CLL αDC1s. Nevertheless, CD70-blocking of αDC1s from both controls and patients with CLL had a negative influence on the production of both IL-12p70 and the Th1 cytokine IFN-γ, while the production of the Th2 cytokine IL-5 was enhanced. Together, this study further suggests that αDC1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL.


Subject(s)
CD27 Ligand/physiology , Dendritic Cells/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , CD27 Ligand/analysis , Cell Polarity , Dinoprostone/analysis , Humans , Interleukin-12/biosynthesis , Th1 Cells/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/physiology
4.
Transplant Cell Ther ; 29(4): 275.e1-275.e5, 2023 04.
Article in English | MEDLINE | ID: mdl-36720458

ABSTRACT

Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplantation (HCT) is usually effective, but the duration of the immunity is unknown. We conducted this study to evaluate humoral immunity to tetanus and diphtheria in long-term survivors and to provide knowledge regarding the need for boosters. The median time from HCT to blood sampling was 14 years (range, 8 to 40 years). All patients had received at least 3 doses of vaccines against both tetanus and diphtheria, either monovalent or combination vaccines containing a full dose of the diphtheria toxoid component. In addition, 1 or more booster doses were administered to 21 of the 146 patients (14%). On enzyme-linked immunosorbent assay, levels <.1 IU/mL for diphtheria and <.01 IU/mL for tetanus were considered low or seronegative. Values between .01 and .5 IU/mL for tetanus and between .1 and 1.0 IU/mL for diphtheria were considered to represent partial protection, and levels >.5 and >1.0 IU/mL were considered high and protective, respectively. In all, 39% of patients were seronegative against diphtheria, 52% had some protection, and 9% had a high titer. In contrast, no patient had become seronegative to tetanus, 32% had "partial protection" against tetanus and 68% had a high titer. In multivariate analysis, active graft-versus-host-disease, sex, or time from sampling did not affect the probability of becoming seronegative or seropositive. Younger age was associated with lower antibody levels to tetanus toxoid, but age was not correlated with antibody levels against diphtheria toxoid. Tetanus immunity was maintained after vaccination in most long-term survivors, but immunity against diphtheria was poor, and boosters should be considered.


Subject(s)
Diphtheria , Hematopoietic Stem Cell Transplantation , Tetanus , Humans , Diphtheria/prevention & control , Tetanus/prevention & control , Antibodies, Bacterial , Tetanus Toxoid , Vaccination , Diphtheria Toxoid , Corynebacterium
5.
Horm Metab Res ; 42(13): 961-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20925018

ABSTRACT

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.


Subject(s)
Addison Disease/blood , Adrenocorticotropic Hormone/blood , Glucocorticoids/blood , Hydrocortisone/blood , Addison Disease/drug therapy , Adult , Cortisone/administration & dosage , Cortisone/analogs & derivatives , Cortisone/therapeutic use , Female , Humans , Hydrocortisone/urine , Male , Saliva/metabolism , Time Factors
6.
Vaccine ; 36(25): 3701-3707, 2018 06 14.
Article in English | MEDLINE | ID: mdl-29748028

ABSTRACT

AIM: To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent pneumococcal conjugated vaccine (PCV13), Prevenar13®, compared to a 23-valent pneumococcal polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response. BACKGROUND: Streptococcus pneumoniae causes substantial morbidity in patients with CLL, a group known to respond poorly to polysaccharide vaccines. Comparative studies with conjugated vaccines are lacking. METHODS: 128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n = 63) or PPSV23 (n = 65) after stratification by IgG level and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, and at one and six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA). RESULTS: PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. PPSV23 did not trigger a better immune response than PCV13 for any of the serotypes, regardless of analysis method or time point of analysis. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated. CONCLUSIONS: In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for most serotypes common for the two vaccines. We therefore propose that PCV13 should be included in vaccination programs against Streptococcus pneumoniae for CLL patients and administered as early as possible during the course of the disease.


Subject(s)
Antibodies, Bacterial/biosynthesis , Immunoglobulin G/biosynthesis , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Aged , Aged, 80 and over , Female , Humans , Immunogenicity, Vaccine , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Pneumococcal Infections/immunology , Pneumococcal Infections/microbiology , Prospective Studies , Random Allocation , Serogroup , Streptococcus pneumoniae/immunology , Vaccine Potency , Vaccines, Conjugate
7.
Bone Marrow Transplant ; 52(3): 431-437, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27941768

ABSTRACT

Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 allografted women, 33 with cGvHD, and 23 of these were on GC therapy. Controls were 94 healthy, age-matched women. Supportive study groups were women after autologous HCT (autoHCT; n=20) and non-transplanted women on GC therapy (n=26). Compared with controls, free testosterone (free T) and dehydroepiandrosterone sulfate (DHEAS) levels were lower in both the alloHCT group and GC groups; P<0.0001 and P<0.05, respectively. Androgens in the autoHCT group were similar or higher than controls. In the subgroup of alloHCT patients without cGvHD, free T was similar to controls (7.2 vs 8.6 pmol/L; P=0.42), whereas DHEAS levels was lower than controls (1.7 vs 2.5 µmol/L; P=0.008). Compared with controls, cGvHD without GC (n=10) was associated with lower free T and DHEAS; P=0.004 and P=0.0004, respectively). The lowest androgen levels were seen in women with both cGvHD and GC therapy. In conclusion, low serum androgens were associated with cGvHD and GC therapy, prompting for studies assessing a possible association between low androgens and sexual dysfunction and quality of life in allografted women.


Subject(s)
Androgens/blood , Dehydroepiandrosterone/blood , Glucocorticoids/administration & dosage , Graft vs Host Disease/blood , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation , Testosterone/blood , Adult , Aged , Aged, 80 and over , Allografts , Chronic Disease , Female , Humans , Middle Aged
8.
Biosens Bioelectron ; 21(10): 1973-80, 2006 Apr 15.
Article in English | MEDLINE | ID: mdl-16289605

ABSTRACT

Real time interactions of antithrombin (AT) with Corline Heparin Surfaces (CHS) with one and two layers of heparin conjugate have been examined using a multi-wavelength TIRF spectroscopy technique with continuous flow. Fluorescently labeled AT, adsorbed from citrated human blood plasma, showed significantly higher signals on CHS compared to the cationic surface used to attach the heparin conjugate. The AT binding to CHS was very stable, also after exposure to soluble heparin at a concentration of 1.5 IU/mL. Only a few percent of the bound AT were displaced from the surfaces by AT present in plasma after long-term exposure to plasma. In contrast, larger amounts of the freshly added AT had adsorbed to the surfaces, especially to the surface with two layers of heparin conjugate, indicating the presence of unsaturated AT binding sites. The amount of AT bound to the different surfaces was quantified after elution using an enzyme immunoassay (EIA). Characteristic emission spectra of proteins and fluorophores of labeled proteins, obtained at the surfaces after a long-term exposure to plasma, confirmed their presence at the surfaces. The multi-wavelength TIRF technique proved to be a useful tool when combined with other techniques to study the time course of interactions of fluorescently labeled proteins with biomaterials, even in a complex environment such as plasma.


Subject(s)
Antithrombins/metabolism , Heparin/metabolism , Spectrometry, Fluorescence/methods , Antithrombins/chemistry , Biosensing Techniques , Heparin/chemistry , Humans
9.
Chem Biol ; 8(7): 661-71, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11451667

ABSTRACT

BACKGROUND: Filamentous bacteriophage are used as general cloning vectors as well as phage display vectors in order to study ligand-receptor interactions. Exposure to biphasic chloroform-water interface leads to specific contraction of phage, to non-infective I- or S-forms. RESULTS: Upon exposure, phage were inactivated (non-infective) at methanol, ethanol and 1-propanol concentrations inversely dependent upon alcohol hydrophobicity. Infectivity loss of phage at certain concentrations of 1-propanol or ethanol coincided with changes in the spectral properties of the f1 virion in ultraviolet fluorescence and circular dichroism studies. CONCLUSIONS: The alcohols inactivate filamentous phage by a general mechanism--solvation of coat protein--thereby disrupting the capsid in a manner quite different from the previously reported I- and S-forms. The infectivity retention of phagemid pG8H6 in 99% acetonitrile and the relatively high general solvent resistance of the phage strains studied here open up the possibility of employing phage display in non-aqueous media.


Subject(s)
Bacteriophages/chemistry , Bacteriophages/growth & development , Combinatorial Chemistry Techniques/methods , Solvents/pharmacology , 1-Propanol/pharmacology , Acetonitriles/pharmacology , Bacteriophages/drug effects , Circular Dichroism , Culture Media , Ethanol/pharmacology , Hydrogen-Ion Concentration , Methanol/pharmacology , Spectrometry, Fluorescence , Temperature
10.
Clin Pharmacol Ther ; 36(2): 197-200, 1984 Aug.
Article in English | MEDLINE | ID: mdl-6744778

ABSTRACT

Several studies have shown that 5 mg amiloride can counteract the hypokalemic effect of 50 mg hydrochlorothiazide (HCTZ). In a double-blind study of 30 subjects with mild to moderate primary hypertension, we determined whether this effect could be obtained with half the dose of amiloride (2.5 mg) in combination with 25 mg HCTZ. The effect of twice the dosage was evaluated in subjects with unsatisfactory blood pressure (BP) on the lower dose. Both 25 mg HCTZ/amiloride 2.5 mg and 25 mg HCTZ alone lowered BP. In subjects with untreated diastolic BP between 110 and 115 mm Hg, these doses were inadequate; twice the dose resulted in a greater reduction in BP. Irrespective of dosage, a potassium-sparing effect resulted from the combination of HCTZ and amiloride, with a reduction in serum potassium levels from HCTZ alone as well.


Subject(s)
Amiloride/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/drug therapy , Potassium/blood , Pyrazines/administration & dosage , Adult , Aged , Amiloride/pharmacology , Blood Pressure/drug effects , Drug Therapy, Combination , Female , Humans , Hydrochlorothiazide/therapeutic use , Male , Middle Aged
11.
Clin Pharmacol Ther ; 28(6): 707-14, 1980 Dec.
Article in English | MEDLINE | ID: mdl-7002427

ABSTRACT

Fifty-five patients with primary hypertension, World Health Organization (WHO) stages I and II, were randomly allocated to a 9-mo multicenter, controlled, double-blind, crossover study with timolol, a nonselective beta adrenoceptor blocker, and hydrochlorothiazide combined with the potassium-sparing drug amiloride (AHCT). In 54% of the patients the blood pressure responded to timolol, in 87% to AHCT, and in 91% to a combination of the two. The diurectic was more effective than the beta blocker in patients with low-renin hypertension, who all responded to AHCT. Overall, there was no correlation between pretreatment plasma renin activity (PRA) and hypothensive effect of either drug. Timolol reduced PRA by 58% and plasma aldosterone (PA) by 23% while AHCT increased these levels threefold. Combination therapy increased PA while PRA returned towards baseline, suggesting greater aldosterone stimulation by the diuretic component. Serum triglycerides rose during timolol treatment alone and in combination. Both timolol and AHCT are effective antihypertensives. In combination they normalize blood pressure in most patients with primary hypertension (WHO stages I and II). Determination of PRA is useful as a guide to the choice of the first treatment in searching out low-renin hypertensive patients, who are best treated with diuretics.


Subject(s)
Amiloride/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/drug therapy , Propanolamines/therapeutic use , Pyrazines/administration & dosage , Timolol/therapeutic use , Adult , Amiloride/therapeutic use , Blood Pressure/drug effects , Double-Blind Method , Drug Evaluation , Drug Therapy, Combination , Female , Humans , Hydrochlorothiazide/therapeutic use , Male , Middle Aged , Renin/blood
12.
Br J Pharmacol ; 106(1): 17-24, 1992 May.
Article in English | MEDLINE | ID: mdl-1504725

ABSTRACT

1. In whole portal veins, ciclazindol (0.3-10 microM) increased the amplitude and duration, but decreased the frequency of spontaneous contractions. Glibenclamide (0.3-10 microM) produced a small increase in contraction amplitude and duration with a small reduction in contraction frequency. 2. In whole portal veins, ciclazindol (1-10 microM) antagonized the relaxant effects of BRL 38227 in a non-competitive manner. Under identical conditions, the effects of glibenclamide (0.3-10 microM) appeared to be competitive. 3. In whole portal veins loaded with 42K, ciclazindol itself (up to 3 microM) had no detectable effect on basal 42K exchange. However, the increase in 42K efflux produced by BRL 38227 (5 microM) was antagonized by ciclazindol (3 microM). Similar effects were produced by glibenclamide (up to 3 microM). 4. In freshly-isolated portal vein cells examined by the whole-cell voltage-clamp technique, ciclazindol (1-100 microM) inhibited the slowly-activating and inactivating transient outward current (ITO) which could be generated at potentials more positive than -30 mV. In addition ciclazindol (1-10 microM) inhibited the non-inactivating K-current (IKCO) induced by BRL 38227 (10 microM). 5. In freshly-isolated portal vein cells under current-clamp conditions, the hyperpolarization produced by BRL 38227 (10 microM) was reversed by ciclazindol (1-10 microM). 6. In porcine brain membrane fragments, glibenclamide (0.65 nM) displaced 50% of the binding of [3H]-glibenclamide whereas ciclazindol (up to 10 microM) had no effect. 7. It is concluded that ciclazindol is a K-channel blocker. Its action is not selective for the channel(s) which carry IKCO but also extends to those which carry ITO.Its inability to displace [3H]-glibenclamide from porcine brain fragments may indicate that antagonism of BRL 38227 by ciclazindol in smooth muscle is exerted at a site different from that of glibenclamide.


Subject(s)
Benzopyrans/antagonists & inhibitors , Indoles/pharmacology , Portal Vein/drug effects , Potassium Channels/drug effects , Pyrroles/antagonists & inhibitors , Vasoconstriction/drug effects , Animals , Cromakalim , Glyburide/metabolism , Glyburide/pharmacology , In Vitro Techniques , Indoles/administration & dosage , Male , Membrane Potentials/drug effects , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Portal Vein/physiology , Potassium/metabolism , Potassium Channels/metabolism , Rats , Rats, Inbred Strains , Vasodilator Agents/antagonists & inhibitors
13.
Drugs ; 36 Suppl 7: 41-9, 1988.
Article in English | MEDLINE | ID: mdl-3076135

ABSTRACT

Infravesical outflow obstruction and bladder hypertrophy are often associated with bladder hyperactivity causing frequency, urge and urinary incontinence. This hyperactivity may be due to a supersensitivity to depolarising stimuli. Drugs that inhibit smooth muscle activity by opening K+ channels, resulting in hyperpolarisation, would therefore seem to be an attractive therapeutic principle. Pinacidil is an effective vasodilator classified as a K+ channel opener. The drug has been shown to effectively depress spontaneous contractile activity, the contractions induced by low (less than 40 mmol/L) concentrations of K+, carbachol and by electrical stimulation of nerves in isolated normal human bladder tissue and also in normal and hypertrophied rat bladder. The effect was more pronounced in hypertrophied detrusor. Pinacidil in concentrations inhibiting muscle activity also increased the efflux of 86Rb in bladder tissue. In vivo pinacidil suppressed spontaneous contractile activity in rats with infravesical bladder obstruction and detrusor hypertrophy. The findings make K+ channel openers an interesting, potentially useful therapeutic principle in hyperactivity associated with bladder hypertrophy.


Subject(s)
Antihypertensive Agents/pharmacology , Guanidines/pharmacology , Muscle, Smooth/drug effects , Urinary Bladder/drug effects , Animals , Humans , Muscle Contraction/drug effects , Pinacidil , Potassium Channels/drug effects
14.
Bone Marrow Transplant ; 30(12): 971-3, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12476293

ABSTRACT

We present a patient with a Philadelphia chromosome positive (Ph+) acute lymphocytic leukaemia (ALL) refractory to standard induction chemotherapy. Treatment with the ABL-specific tyrosine kinase inhibitor STI571 (Glivec, Gleevec, imatinib mesylate) resulted in a complete haematologic and cytogenetic remission. Allogeneic stem cell transplantation from an unrelated donor could be undertaken while the patient was in STI571-induced complete remission from the leukaemia. At present, the patient has a 15-month post-transplantation follow-up and is in stable molecular remission as evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for the BCR/ABL fusion gene transcript. Our case demonstrates that STI571 can act as a bridge to potentially curative allogeneic stem cell transplant in otherwise poor prognosis Ph+ ALL.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Enzyme Inhibitors/therapeutic use , Peripheral Blood Stem Cell Transplantation , Piperazines/therapeutic use , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyrimidines/therapeutic use , Adult , Amsacrine/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Benzamides , Betamethasone/administration & dosage , Biomarkers, Tumor/genetics , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Female , Fusion Proteins, bcr-abl/genetics , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Humans , Imatinib Mesylate , Immunosuppressive Agents/therapeutic use , Mitoxantrone/administration & dosage , Neoplasm, Residual , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Remission Induction , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Homologous , Vincristine/administration & dosage
15.
Leuk Lymphoma ; 43(12): 2351-3, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12613523

ABSTRACT

Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK + anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was hot possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/administration & dosage , Lymphoma, Large-Cell, Anaplastic/drug therapy , Salvage Therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Humans , Lymphoma, Large-Cell, Anaplastic/radiotherapy , Male , Palliative Care , Recurrence , Remission Induction
16.
Thromb Res ; 107(3-4): 135-9, 2002 Aug 15.
Article in English | MEDLINE | ID: mdl-12431479

ABSTRACT

In most, but not all, cases of chronic idiopathic thrombocytopenic purpura (ITP), bleeding complications are known to occur when the platelet count is low. The present study investigates the effect of ITP sera on the in vitro platelet function of donor platelets. Sera from 58 ITP patients were investigated. Using an indirect monoclonal antibody specific immobilisation of platelet antigen (MAIPA) technique, GPIIb/IIIa and GPIb/IX specific antibodies were found in 23 and 20 patients, respectively. Twelve of them had antibodies against both glycoprotein (GP) complexes. The ITP sera's effect on donor platelets was investigated by aggregometry and the results were compared with the ones of 26 healthy donor sera. Grouped together, the ITP sera significantly impaired the ADP-induced platelet aggregation of donor platelets compared to the control sera; the mean relative aggregation response (T(max)) seen for the ITP and control sera were 82 +/- 21% and 92 +/- 7%, respectively (p = 0.0157). However, 6 ITP sera gave an enhanced aggregation response, whereas 17 ITP sera resulted in an impaired platelet aggregation, when using the mean +/- 2 S.D. recorded for the controls as the normal range. There was not any correlation between aggregation response, platelet number or the presence of GPIb/IX or GPIIb/IIIa specific antibodies, other than the fact that all ITP sera causing an enhanced aggregation were from patients with a platelet number less then 100 x 10(9)/l at the time of blood sampling. It is concluded that some ITP sera can either enhance or impair the platelet aggregation response, but in most cases, a normal response is obtained.


Subject(s)
Platelet Aggregation , Platelet Membrane Glycoproteins , Purpura, Thrombocytopenic, Idiopathic/blood , Adenosine Diphosphate/pharmacology , Adolescent , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Case-Control Studies , Female , Humans , Kinetics , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation/immunology , Platelet Count , Platelet Glycoprotein GPIIb-IIIa Complex/immunology , Platelet Glycoprotein GPIb-IX Complex/immunology
17.
Curr Med Res Opin ; 6(8): 513-7, 1980.
Article in English | MEDLINE | ID: mdl-7389382

ABSTRACT

The efficacy of 500 mg pivampicillin twice daily, 350 mg pivampicillin 3-times daily and 100 mg doxycycline daily was compared in 106 patients with salpingitis, parametritis or endometritis. Both the pivampicillin regimens were equally effective. The average duration of therapy needed to produce a satisfactory clinical response was shorter with pivampicillin (14 days) than with doxycycline (21 days). Pivampicillin improved the patients' gynaecological status in 90% of the subjects treated compared to only 70% of patients given doxycycline. Fewer relapses were recorded in women given pivampicillin (4%) than in subjects treated with doxycycline (15%). Gonococci were isolated from 10% of vaginal swabs. The involvement of Chlamydia and Mycoplasma was not studied. However, the high cure rate indicated that, if present, they did not pose a therapeutic problem. Side-effects, mainly dyspepsia, were observed in 2 patients in each group. The twice-daily administration of pivampicillin is recommended, since it is more practical and increases patient compliance.


Subject(s)
Ampicillin/analogs & derivatives , Doxycycline/therapeutic use , Endometritis/drug therapy , Parametritis/drug therapy , Pivampicillin/therapeutic use , Salpingitis/drug therapy , Adult , Bacterial Infections/drug therapy , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans
18.
Photochem Photobiol ; 74(4): 549-57, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11683034

ABSTRACT

By means of steady-state fluorescence spectroscopy we explore the photophysics of two lowest lying singlet excited states in two natural 15-cis-carotenoids, namely phytoene and phytofluene, possessing three and five conjugated double bonds (N), respectively. The results are interpreted in relation to the photophysics of all-transcarotenoids with varying N. The fluorescence of phytofluene is more Stokes-shifted relative to that of phytoene, and is ascribed to the forbidden S1-->S0 transition, with its first excited singlet state (S1) lying 3340 cm-1 below the dipole allowed second excited singlet state (S2), at 77 K. For phytoene the S2 and S1 potential surfaces are closer in energy, probably giving rise to the mixed S2 and S1 fluorescence characteristics. The origin of phytoene fluorescence is discussed and is suggested to be due to the S1-->S0 transition; with the S1 state located 1100 cm-1 below S2 at 77 K. The dependence of the fluorescence quantum yield on temperature and viscosity shows that large amplitude molecular motions are involved in the radiationless relaxation process of phytoene. The transition dipole moment of absorption and emission are parallel in phytoene and nonparallel in phytofluene.


Subject(s)
Carotenoids , Algorithms , Carotenoids/chemistry , Carotenoids/isolation & purification , Molecular Structure , Photochemistry , Rhodospirillum rubrum/metabolism , Spectrometry, Fluorescence , Spectrophotometry, Atomic , Stereoisomerism
19.
Diabetes Res Clin Pract ; 13(1-2): 53-61, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1773714

ABSTRACT

The interference of background characteristics with quality of life and metabolic control in patients with insulin-dependent diabetes mellitus (IDDM) were examined. Seventy-three consecutive outpatients who switched from syringe injections to multiple pen-injection treatment comprised the study group. Perceived status as well as retrospective changes in quality of life, attributed to the new treatment modality, were assessed at follow-up after 9-13 months. Data on metabolic control (HbA1C) were collected at base-line and follow-up. Sub-group comparisons in life quality and metabolic control were performed with regard to differences in sex, age, cohabitation, onset and duration of IDDM. Most of the background characteristics had no or just minor significance for status and change in the life quality and metabolic control of the patients. Cohabitation, however, was linked to a better life quality status pertaining to different domains and a tendency to better metabolic control. In addition, females reported a slightly better health status and a more healthy life style (i.e. eating, drinking and smoking habits) than did males. Extra treatment attention may therefore be justified for non-cohabiting males.


Subject(s)
Diabetes Mellitus, Type 1/psychology , Quality of Life , Adult , Age Factors , Diabetes Mellitus, Type 1/metabolism , Family Characteristics , Female , Humans , Male , Sex Factors
20.
Diabetes Res Clin Pract ; 36(3): 169-72, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9237783

ABSTRACT

A second follow-up of metabolic control and quality of life in insulin dependent diabetes mellitus (IDDM) patients who had switched 3 years before from syringe to multiple pen injection treatment, was carried out. A total of 73 consecutive outpatients were enrolled in the initial follow-up study in 1988, 1 year after their changeover to insulin pen, with their metabolic control and quality of life examined. The present study concerns the reexamination of 65 of them in 1990. Their HbA(1c) level was recorded yearly, already from 1987, on. After an enhancement of metabolic control in 1988, exhibited primarily by patients with fewer syringe injections before pen treatment, control up to 1990 was found to have regressed to about baseline level or to have gradually declined. Patients who perceived their ability to self-test blood glucose to have decreased exhibited the least satisfactory course of metabolic control. This is seen to indicate that maintaining self-testing in multiple injection insulin treatment is a very real challenge to this regimen.


Subject(s)
Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Quality of Life , Adolescent , Adult , Aged , Diabetes Mellitus, Type 1/psychology , Female , Follow-Up Studies , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Injections, Subcutaneous/instrumentation , Insulin/therapeutic use , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care , Prospective Studies , Retrospective Studies , Self Administration , Time Factors
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