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M Wysocki

Publications and source records attributed to M Wysocki.

At least 37 records · Page 2Linked to original sources

[Methotrexate resistance in acute leukemias].

Methotrexate is an important cytostatic drug in therapy of acute lymphoblastic leukemia. Cellular resistance to methotrexate might cause treatment failure. Possible mechanisms of resistance to methotrexate include: decreased accumulation and retention, decreased intracellular polyglutamylation, increased level or mutations of target enzymes, resistance to apoptosis. The literature review shows that resistance to methotrexate might be circumvented by continuous drug infusion in T-ALL, relapsed ALL and in AML. Another possibility to overcome mechanisms of resistance is the use of rationally designed new antifolates, which: can bypass RFC-mediated drug transport, are not dependent on polyglutamylation, have an improved affinity to target enzymes and target also other enzymes.

Acute Disease↗

Candesartan cilexetil and renal hemodynamics in hypertensive patients.

This randomized, double-blind, placebo-controlled crossover study evaluated the effects of the angiotensin II type 1 (AT1)-receptor blocker candesartan cilexetil on renal blood perfusion and glomerular filtration in patients with primary hypertension with diastolic blood pressure of 100 to 114 mm Hg. After a 4-week placebo run-in period, patients were randomized to receive either 16 mg candesartan cilexetil or placebo once daily for 6 weeks, after which they were switched to the alternative treatment. At the end of each period, 24 h after the last dose, renal assessments were made and the plasma renin activity, plasma concentrations of angiotensin II, aldosterone, and catecholamines were measured. Compared with placebo, candesartan cilexetil significantly reduced mean arterial pressure, by 8 mm Hg (95% confidence interval [CI], 3;12). Renal vascular resistance was significantly reduced by 0.03 mm Hg/mL min(-1) (95% CI, 0.01; 0.06). There was a small nonsignificant increase in renal plasma flow. The filtration fraction fell slightly from 0.24 to 0.22 (95% CI, -0.00, 0.04). As expected, angiotensin II concentrations and plasma renin activity were increased and the aldosterone concentrations were reduced. Catecholamine concentrations were unaffected. In conclusion, 6 weeks' treatment with 16 mg candesartan cilexetil once daily induced a reduction of renal vascular resistance and a trend toward increased renal plasma flow despite a reduction in mean arterial pressure. Because the glomerular filtration rate was maintained the filtration fraction was reduced, indicating a decreased glomerular capillary pressure.

Adult↗

Pleomorphic adenoma and adenolymphoma in ultrasonography.

OBJECTIVE: The aim of the study was to define ultrasonographic morphologic features characteristic of pleomorphic adenoma and adenolymphoma (Warthin's tumor). METHODS: Documentation of 31 ultrasonographic examinations of 20 pleomorphic adenomas and 10 Warthin's tumors in 28 patients was analysed. All cases were confirmed by fine needle aspiration biopsy or/and histopathological examination. Estimated ultrasound criteria were: borders (well-defined, predominantly well-defined, ill-defined), shape (lobulated, oval, irregular), echogenicity (increased, decreased), structure (homogeneous, slightly inhomogeneous, inhomogeneous) and presence of irregular anechoic areas within a tumor. RESULTS: 100% of the lesions were hypoechoic. 80.6% of all tumors were well-defined. The remaining 19.4% had predominantly well-defined borders. 55% of pleomorphic adenomas had a lobulated shape. Almost equal percentages of Warthin's tumors were lobulated, had an oval and irregular shape. Irregular echolucent areas were present in six of 11 examinations of Warthin's tumors and in one pleomorphic adenoma. CONCLUSIONS: Ultrasonography is a useful method for the evaluation of pleomorphic adenomas and Warthin's tumors and sometimes it might allow to suggest the nature of a tumor if a certain sonographic pattern is present.

Adenolymphoma↗

In vitro drug resistance profiles of adult versus childhood acute lymphoblastic leukaemia.

The difference in the current cure rates between adult and childhood acute lymphoblastic leukaemia (ALL) may be caused by differences in drug resistance. Earlier studies showed that in vitro cellular drug resistance is a strong independent adverse risk factor in childhood ALL. Knowledge about cellular drug resistance in adult ALL is still limited. The present study compared the in vitro drug resistance profiles of 23 adult ALL patients with that of 395 childhood ALL patients. The lymphoblasts were tested by the MTT assay. The group of adult ALL samples was significantly more resistant to cytosine arabinoside, L-asparaginase, daunorubicin, dexamethasone and prednisolone. The resistance ratio (RR) was highest for prednisolone (31.7-fold) followed by dexamethasone (6.9-fold), L-asparaginase (6. 1-fold), cytosine arabinoside (2.9-fold), daunorubicin (2.5-fold) and vincristine (2.2-fold). Lymphoblasts from adult patients were not more resistant to mercaptopurine, thioguanine, 4-HOO-ifosfamide, mitoxantrone and teniposide. There were no significant differences in drug resistance between adult T-cell (T-) ALL (n = 11) and adult common/pre-B-cell (B-) ALL (n = 10). Additionally, adult T-ALL did not differ from childhood T-ALL (n = 69). There were significant differences between adult common/pre-B-ALL and childhood common/pre-B-ALL (n = 310) for prednisolone (RR = 302, P = 0.008), dexamethasone (RR = 20.9, P = 0.017) and daunorubicin (RR = 2.7, P = 0.009). Lymphoblasts from adults proved to be relatively resistant to drugs commonly used in therapy. This might contribute to the difference in outcome between children and adults with ALL.

Adolescent↗

[Non-invasive ventilation in acute respiratory insufficiency].

Non invasive mechanical ventilation represents all the techniques of mechanical ventilation not using endotracheal connection to the respirator. Non invasive mechanical ventilation is essentially represented nowadays by facial (generally used for acute respiratory failure) and nasal ventilation (widely used for long term mechanical ventilation at home). Following in France the first studies of Rideau in the '80 in patients with chronic respiratory failure secondary to muscular dystrophy, Meduri, then Brochard demonstrated the interest of non invasive mechanical ventilation in the management of acute on chronic respiratory failure. A simple algorithm is thus able to recommend in first attempt use of non invasive mechanical ventilation in acute on chronic respiratory failure except if the patient presents in a severe respiratory status imposing in first line endotracheal ventilation. In parallel, more recent studies have demonstrated the interest of that technique in immediate ventilatory link in the spectrum of weaning of endotracheal mechanical ventilation. In hypoxic acute respiratory failure, non invasive mechanical ventilation remains controversial and seems to be better indicated in moderate to severe respiratory status.

Acute Disease↗

[Bone marrow cellularity in acute lymphoblastic leukemia of children].

The early response to therapy in childhood acute lymphoblastic leukemia (ALL) is typically assessed by bone marrow status. The clearance of blast cells in peripheral blood and bone marrow during induction therapy was analysed in 38 children (27 precursor-B-ALL and 11 precursor T-ALL) treated according to BFM90 or New York 93 protocols. Leukocyte count and peripheral blood smear taken at diagnosis, day 8, day 14 and day 33 as well as bone marrow cellularity and percentage of blasts on days: 0, 14, 33 were analysed. The number of blasts in bone marrow was correlated to bone marrow cellularity (Spearman's rho = 0.72, p = 0.001). Patients with T-ALL were more frequently resistant to steroids in vivo and reached remission later in comparison to precursor-B-ALL children (p = 0.019), however blasts reduction ratio was comparable in both lineages. Bone marrow cellularity on days 14 and 33 of induction therapy was similar.

Adolescent↗

[High risk acute lymphoblastic leukaemia in children. Preliminary report after introducing a new version of New York (1997) protocol adjusted to the age of the patients. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group].

The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed.

Adolescent↗

[Preliminary results of BFM 96 protocol in treatment of childhood ALL relapse in the experience of the Polish Paediatric Leukaemia /Lymphoma Study Group].

Between 1998 and 1999, 36 children aged from 3 months to 18 years (10 girls and 26 boys) with first relapse of acute lymphoblastic leukaemia were included in the study. The children were treated according to the BFM 96 relapse protocol. There were 24 cases with early (including 9 children with very early) and 12 cases with late relapse ( BM-20, local extra BM-6, combined 10). The overall second complete remission (CR) rate was 83,33%. The probability of overall EFS after 2 years was 73,3%. The results obtained with BFM 96 chemotherapy in children with first late relapse are acceptable. For children with early relapses, megachemotherapy with BMT in second remission should be used.

Adolescent↗

[Results of treatment of children with chronic myelogenous leukaemia (CML) obtained by the Polish Paediatric Leukaemia/Lymphoma Study Group].

Retrospective analysis of 102 children with CML from 9 paediatric centres in Poland has been performed. A total number of 102 children: 58 boys and 44 girls aged 1-17 years (median 9.4 years old) with CML, treated in the period 1975-1999 were included in the study. Forty eight of 102 (47.1 %) children were treated with cytostatic drugs without IFN alpha: busulfan, hydroxyurea, 6-mercaptopurine or etoposide (VP-16). Fifty four of 102 (52.9%) patients were treated with interferon alpha (IFN alpha) after cytoreductive pretreatment. Thirty out of 102 (29.4%) patients underwent stem cell transplantation (SCT): 24 - matched related donor allo-BMT, 2 - matched unrelated donor allo-BMT, 1 - partially matched related donor T-cell depleted allo-PBPCT, 1 - syngeneic allo-BMT and 2 - autologous PBPCT. Overall survival analysis revealed that 46 of the 102 (45.1%) children remained alive: 5/35 (14.3%) children treated with cytostatics alone, 22/37 (59.5%) children treated with IFN alpha and 19/30 (63.3%) children treated with SCT. Among SCT survivors there are 10/17 (58.8%) children treated with IFN alpha prior to SCT and 9/13 (69.2%) children treated with cytostatics alone prior to SCT. The probability of 5-year survival is 0.51 in the group treated with SCT (median follow-up 58 months); 0.43 in the group treated with IFN alpha (median follow-up 53 months) and 0.23 in the group treated with cytostatics (median follow-up 31 months). Our data show, that BMT is the treatment of choice in CML in children. IFN alpha could be successfully applied as an alternative treatment for those, who do not have a suitable donor for allogeneic SCT. Better outcome in post BMT children, who were not treated with IFN alpha prior to SCT requires confirmation by studies on larger groups of patients. However, it seems to be justified to stop IFN alpha therapy at least 3 months before SCT. The main reason for unsuccessful treatment outcome in patients with CML in Poland remains the still insufficient access to MUD-BMT.

Adolescent↗

[Abdominal presentation of B-cell non-Hodgkin's lymphoma (B-NHL) - surgical treatment and its results. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group].

The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.

Abdominal Neoplasms↗

[Adverse reactions associated with the use of L-asparaginase during therapy of patients with nB non-Hodgkin's lymphoma. Report of the Polish Paediatric LeuKaemia/Lymphoma Study Group].

The aim of the study was to determine the side effects of asparaginase administration during treatment protocol for childhood non-Hodgkin's lymphoma (NHL). Drug adverse reactions occurred in 20/66 of patients (30,3%) treated in 9 centres in Poland between 1993 and 1998. The most common side effects were coagulation disturbances in 12/66 of the children (18,2%), which occurred due to reduced production of important coagulation factors. Six patients (9,1%) developed impairment of liver function (9,1%). Drug toxicity caused the modifications of treatment protocol in 12/66 (18,2%) of patients, mainly in the induction phase; 3 children died due to relapse of disease.

Adolescent↗

[Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group].

Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland.

Adolescent↗

[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms].

A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.

Adolescent↗

[Underestimation of medical activity measured by daily activity scores].

OBJECTIVES: To assess the effectiveness of a scoring system (omega) for medical activity. METHODS: In 100 consecutive patients (phase A), the omega scores were calculated by the physician in charge and controlled by an independent physician. In 100 additional patients, the omega scores were controlled again while using corrective measures (phase B). RESULTS: Phase A: at least one item was forgotten in 54% of the stays. The amount of medical activity lost (MAL) was 14 +/- 13%. Phase B: there was no significant reduction in the number of stays with forgotten items (45%, p = 0.41 vs phase A) and the MAL was 17 +/- 16% (p = 0.19 vs 6 +/- 10 days, p = 0.002) and high omega II score (items recorded every time they are performed) (0.8 +/- 1.3 vs 0.4 +/- 0.7, p = 0.01) were associated with forgetting items. The MAL was negatively correlated with the length of stay (r = -0.69, p < 0.001) and omega score (r = -0.40, p = 0.001). CONCLUSION: In routine practice, scoring systems may underestimate medical activity.

Activities of Daily Living↗

Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients. SRLF Collaborative Group on Mechanical Ventilation. Société de Réanimation de Langue Française.

OBJECTIVE: To evaluate the prevalence and outcome of the acute respiratory distress syndrome (ARDS) among patients requiring mechanical ventilation. DESIGN: A prospective, multi-institutional, initial cohort study including 28-day follow-up. SETTINGS: Thirty-six French intensive care units (ICUs) from a working group of the French Intensive Care Society (SRLF). PATIENTS: All the patients entering the ICUs during a 14-day period were screened prospectively. Hypoxemic patients, defined as having a PaO(2)/FIO(2) ratio (P/F) of 300 mmHg or less and receiving mechanical ventilation, were classified into three groups, according to the Consensus Conference on ARDS: group 1 refers to ARDS (P/F: 200 mmHg or less and bilateral infiltrates on the chest X-ray); group 2 to acute lung injury (ALI) without having criteria for ARDS (200 < P/F </= 300 mmHg and bilateral infiltrates) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups. RESULTS: Nine hundred seventy-six patients entered the ICUs during the study period, 43 % of them being mechanically ventilated and 213 (22 %) meeting the criteria for one of the three groups. Among all the ICU admissions, ARDS, ALI and group 3 patients amounted, respectively, to 6.9 % (67), 1.8 % (17) and 13.3 % (129) of the patients, and represented 31.5 %, 8.1 % and 60.2 % of the hypoxemic, ventilated patients. The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others (60 % vs 31 % p < 0.01). In group 3, 42 patients had P/F less than 200 mmHg associated with unilateral lung injury; mortality was significantly lower (40.5 %) than in the ARDS group. In the whole group of hypoxemic, ventilated patients, septic shock and severity indices but not oxygenation indices were significantly associated with mortality, while the association with immunosuppression revealed only a trend (p = 0.06). CONCLUSIONS: In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high.

Adult↗