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Biomedical subjects

T Nousiainen

Publications and source records attributed to T Nousiainen.

At least 37 records · Page 2Linked to original sources
PubMed2003

BEAC or BEAM for high-dose therapy in patients with non-Hodgkin's lymphoma? A single centre analysis on toxicity and efficacy.

High-dose chemotherapy supported by autologous stem cell transplantation is widely used in patients with non-Hodgkin's lymphoma (NHL). Limited data is available on the comparative toxicity and efficacy of various high-dose regimens applied in NHL. We therefore analysed regimen-related toxicity and outcome in 71 consecutive NHL patients who received either BEAC (N = 36) or BEAM (N = 35) supported by peripheral blood progenitor cell infusion plus granulocyte colony-stimulating factor. The patients who received BEAM had significantly more often WHO grade > 2 mucositis (63 vs. 28%, P = 0.009) and diarrhoea grade >2 (29 vs. 8%, P = 0.062). Septicaemia also tended to be more frequent and the peak CRP value was higher in the BEAM group (140 vs. 113 mg/l, P = 0.034). Transplant-related mortality (< 100 d) was 3 and 9% in the BEAC and BEAM groups, respectively. No significant differences were observed in overall survival or progression free survival between these two groups. While BEAC and BEAM appears to have equal antitumour efficacy in patients with NHL, BEAM seems to be more toxic to the gastrointestinal tract. However, randomised studies are needed for more definitive conclusions on the relative merits of various high-dose regimens in patients with NHL.

Adolescent↗
PubMed2002

Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients.

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg x m(-2)) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg x m(-2). Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction < or =50%. Twenty-eight patients received doxorubicin > or =400 mg x m(-2) and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m(-2). Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction < or =50% in 10 patients (36%). Left ventricular ejection fraction decreased from 56+/-1.5% to 53.6+/-1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8+/-2.4% to 41.8+/-2.0% (P<0.001) in patients with cardiotoxicity. For patients who developed cardiotoxicity, the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg x m(-2) was highly significant (left ventricular ejection fraction 49.7+/-1.8%, P=0.001 vs baseline). In receiver operator characteristic analysis, the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg x m(-2) for predicting cardiotoxicity in all patients was 0.858. The decrease in left ventricular ejection fraction of more than 4% units after a cumulative doxorubicin dose of 200 mg x m(-2) had a 90% sensitivity and 72% specificity for predicting later cardiotoxicity. Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early, already at low cumulative doxorubicin doses. This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity.

Adult↗
PubMed2002

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction.

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Adult↗
PubMed2002

Recurrent Sphingomonas paucimobilis -bacteraemia associated with a multi-bacterial water-borne epidemic among neutropenic patients.

A cluster of septicaemias due to several water-related species occurred in a haematological unit of a university hospital. In recurrent septicaemias of a leukaemic patient caused by Sphingomonas paucimobilis, genotyping of the blood isolates by use of random amplified polymorphic DNA-analysis verified the presence of two distinct S. paucimobilis strains during two of the separate episodes. A strain of S. paucimobilis identical to one of the patient's was isolated from tap water collected in the haematological unit. Thus S. paucimobilis present in blood cultures was directly linked to bacterial colonization of the hospital water system. Heterogeneous finger-printing patterns among the clinical and environmental isolates indicated the distribution of a variety of S. paucimobilis clones in the hospital environment. This link also explained the multi-microbial nature of the outbreak.

Bacteremia↗
PubMed2002

A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients.

To evaluate feasibility and potential efficacy of amifostine (AMI) in the prevention of toxicities associated with high-dose melphalan (MEL), ten myeloma patients received AMI 910 mg/m2 in 15 min infusion preceding MEL 200 mg/m2 followed by stem cell infusion (AMI group). Hematologic and extra-hematologic toxicities as well as the need for supportive care observed in the AMI group were compared with ten myeloma patients treated in an identical protocol but without AMI. Hypotension was the most important adverse event of AMI infusion. No differences were observed in the time of engraftment between the AMI group and the control group neither was there any difference in the need for supportive care. Oral mucositis grade >2 was observed in 30% of the patients in both groups. Diarrhea grade >2 occurred only in two AMI patients but in five control patients. AMI preceding high-dose MEL is feasible, although adverse events are observed in some patients. Whether AMI could reduce the gastrointestinal toxicity associated with high-dose MEL can be reliably assessed only in prospective randomized trials.

Adult↗
PubMed2001

Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake.

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.

3-Iodobenzylguanidine↗
PubMed2001

Comparison of echocardiography and radionuclide ventriculography in the follow-up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy.

OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS: University hospital. SUBJECTS: A total of 28 adult patients who received doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7% (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement -2.1% units for LVEF determinations with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow-up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.

Adult↗
PubMed2001

Neuroendocrine changes during the evolution of doxorubicin-induced left ventricular dysfunction in adult lymphoma patients.

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Adult↗
PubMed2000

Feasibility and toxicity of high-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly patients (>/=60 years) with non-Hodgkin's lymphoma: comparison with patients <60 years treated within the same protocol.

Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.

Adolescent↗
PubMed2000

Autologous peripheral blood stem cell transplantation in a patient with severe mixed connective tissue disease.

A 65-year old man with mixed connective tissue disease (MCTD) and severe therapy resistant polymyositis was considered for high-dose cyclophosphamide (200 mg/kg) supported by autologous stem cell transplantation (ASCT). During a 21 months follow-up there has been a significant subjective, but objectively only a slight improvement in muscle strength. Initially the levels of serum creatine kinase and serum aldolase normalised, but are at 21 months at about the same level as before ASCT. Based on histopathological examination there is still active myositis. Our case would suggests that this treatment may have some efficacy in MCTD with severe polymyositis although longer follow-up is needed.

Aged↗
PubMed1999

Procalcitonin concentrations in patients with neutropenic fever.

To assess the usefulness of markers of inflammation in distinguishing bacterial infection from severe systemic nonbacterial inflammation, concentrations of procalcitonin, neopterin, endotoxin, tumor necrosis factor, and interleukin-6 were measured in 28 neutropenic patients at the onset of fever and twice thereafter at 4 h intervals. Infection was found in 11 patients, and 17 patients had fever of undetermined origin. The procalcitonin concentration increased rapidly in patients with infection: the response was detectable within 8 h of the onset of fever. Procalcitonin is a specific but not a sensitive marker of infection in patients with neutropenic fever. Its poor sensitivity was related to an absent or delayed response in patients with gram-positive infections. Considerable overlap between infected and noninfected patients was found in levels of endotoxin, tumor necrosis factor, and interleukin-6.

Adult↗