Acute Myeloid Leukaemia:New Targets and Therapies

The most common acute hematological malignancy in adults is acute myeloid leukaemia (AML), accounting for more than 80% of cases in patients over 60 years of age [...

Prognostic factors in patients surgically treated after hip fracture

Wstęp: Osteoporoza z racji zmian demograficznych oraz nieprawidłowego stylu życia społeczeństw rozwiniętych stała się poważnym problemem społecznym. Złamanie bliższego końca kości udowej stanowi jej najpoważniejsze powikłanie, związane z dużą śmiertelnością lub trwałymi następstwami. Celem pracy była ocena wpływu wybranych czynników socjoekonomicznych i czasu interwencji chirurgicznej na rokowanie. Materiał i metody: W badaniu uczestniczyło 148 pacjentów (114 kobiet i 34 mężczyzn) w wieku od 48 do 93 lat, po operacyjnym leczeniu złamania bliższego końca kości udowej, wśród których przeprowadzono badanie ankietowe. Wyniki: W trakcie rocznej obserwacji zmarło 34 pacjentów, co stanowiło 23% badanej grupy. Kolejnych porównań dokonano w dwóch grupach. Wśród 114 pacjentów, którzy przeżyli roczną obserwację (grupa A) oraz w grupie pacjentów, którzy zmarli (grupa B). Średnia wieku pacjentów z grupy A wynosiła 76,3 lata , a dla pacjentów grupy B &#8212; 82,6 lat (p < 0,05). W grupie A przed złamaniem 79,8% pacjentów deklarowało pełna samodzielność, w porównaniu do 44,1 % w grupie B (p < 0,05). Regularnie uprawiało różne formy aktywności fizycznej 39,5% z grupy A i 11,8% w grupie B (p < 0,05). Aktywne spędzaniu czasu poza domem zgłaszało 32,5 % chorych w grupie A vs 14,7% w grupie B. Złamanie wpłynęło niekorzystnie na sytuację materialną pacjentów. Nie stwierdzono zależności między szybkością operacji a rokowaniem pacjentów. Wnioski: 1. Złamanie bliższego końca kości udowej mimo zastosowania leczenia zabiegowego nadal obarczone jest dużym ryzykiem zgonu. 2. Duża aktywność fizyczna, szczególnie poza domem, samodzielność oraz posiadanie partnera wpływają korzystnie na rokowanie pacjentów po złamaniu bliższego końca kości udowej. 3. Złamanie bliższego końca kości udowej ma negatywny wpływ na sytuację materialną pacjentów. 4. Szybkość interwencji chirurgicznej po złamaniu bliższego końca kości udowej nie ma wpływu na przeżywalność. (Endokrynol Pol 2013; 64 (2): 108&#8211;113)Introduction: By the impact of demographic changes and as the result of the &#8216;incorrect&#8217; lifestyles pursued in developed societies, osteoporosis has become a serious social problem. Hip fracture is the most serious complication of osteoporosis and is associated with high mortality rates or permanent health impairment. The goal of this study was an evaluation of the impact of selected socio-economic factors and of the time period from fracture to surgical intervention on the patient&#8217;s prognosis. Material and methods: A group of 148 patients (114 women and 34 men) participated in the study, their age varying between 48 and 93 years, all of them after surgical treatment of hip fracture. A questionnaire study was carried out, encompassing all the participants. Results: During a year-long follow up, thirty-four (34) patients, i.e. 23% of the whole group, passed away. Further comparisons were performed between two groups: Group A &#8212; 114 patients, who survived the follow up period, and Group B &#8212; those who died. The mean age of patients was 76.3 and 82.6 years in Groups A and B, respectively (p < 0.05). In Group A, 79.8% of the patients declared full self-dependence prior to fracture episode vs. 44.1% of the patients in Group B (p < 0.05). Regular physical activity &#8212; in various forms &#8212; was undertaken by 39.5% of the patients in Group A and 11.8% of those in Group B (p < 0.05). Active ways of spending outdoor time were reported by 32.5% of the patients in Group A vs. 14.7% in Group B (p < 0.05). Fracture unfavourably influenced the material situation of affected patients. No relationship was found between the time period from fracture to surgery and the patient&#8217;s prognosis. Conclusions: 1. Despite the currently available surgical treatment methods, hip fracture is still laden with a high risk of fatality. 2. High physical activity, especially outdoors, self-dependence and having a partner positively influence patient&#8217;s prognosis after hip fracture. 3. Hip fracture negatively changes the material situation of patients. 4. The length of time from hip fracture to operation has no effect on the survival rate. (Endokrynol Pol 2013; 64 (2): 108&#8211;113

Technical and economic aspects of revitalization of down-town tenement-houses in Wrocław

In the paper the authors examined the relations between the physical deterioration degree and the price of the tenement-houses in Wrocław. The researches concern the year’s 1991–2009. According to the following analyses: technical, technical-economic (concerning the relations between buildings technical condition and buildings price) and economic the authors have come the conclusions concerning the sensibility of the revitalization work. The authors also estimated the purchase limit profitability of the tenement-houses, which are going to be repaired and modernized or to be demolished and next to be built a new tenement-house. The direction of the engineering activities was shown. They could improve the economic effectiveness of the revitalized tenement-houses

The use of 1α,25-dihydroxyvitamin D3 as an anticancer agent

The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1α,25-dihydroxyvitamin D3 (1,25D) has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues

Wpływ kompetencji społecznych lekarzy na stosowanie się do zaleceń lekarskich przez pacjentów przyjmujących leki na osteoporozę – badanie na grupie Polek po menopauzie

Objective: The aim of the study was to examine the impact of social competence of physicians on the effectiveness of patient compliance and persistence with therapy. Material and methods: The study included physicians and their patients, previously diagnosed with osteoporosis, and eligible to receive pharmacological treatment. The physicians were evaluated with the Social Competence Questionnaire involving three dimensions: social exposure, intimacy and assertiveness, as well as in the combined scale. All patients in the study group were prescribed the same medication: alendronate once a week. Compliance and persistence of the patients were juxtaposed with social interaction skills of physicians during 7 scheduled appointments at 2-month intervals. Results: Doctor’s effectiveness in situations demanding close interpersonal contact was higher in the group with good compliance - group A (pIntencją autorów było zbadanie wpływu kompetencji społecznych lekarza na wytrwałość pacjenta w leczeniu oraz poziom stosowania się chorego do zaleceń lekarskich. Materiał i metody: Projekt badania zakładał udział lekarzy oraz pacjentów, z uprzednio zdiagnozowaną osteoporozą, bez przeciwwskazań do farmakologicznego leczenia osteoporozy. Poziom kompetencji społecznych lekarzy oceniono przy użyciu Kwestionariusza Kompetencji Społecznych (KKS), w 3 wymiarach: Intymność, Ekspozycja Społeczna, Asertywność oraz w Skali Łącznej. Wszyscy pacjenci otrzymali receptę na ten sam lek- alendronian przyjmowany raz w tygodniu. Poprawność stosowania się do zaleceń i wytrwałość w terapii analizowano względem poziomu kompetencji społecznych lekarzy, podczas 7 wizyt pacjentów w dwumiesięcznych odstępach. Wyniki: Efektywność działań lekarzy w sytuacjach wymagających bliskiego interpersonalnego kontaktu była wyższa w grupie A- pacjentów dobrze współpracujących (

Biological evaluation of double point modified analogues of 1,25-Dihydroxyvitamin D₂ as potential anti-leukemic agents

Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist

Regulation of vitamin D receptor expression by retinoic acid receptor alpha in acute myeloid leukemia cells

AbstractAcute myeloid leukemia (AML) is the predominant acute leukemia among adults, characterized by an accumulation of malignant immature myeloid precursors. A very promising way to treat AML is differentiation therapy using either all-trans-retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D), or the use of both these differentiation-inducing agents. However, the effect of combination treatment varies in different AML cell lines, and this is due to ATRA either down- or up-regulating transcription of vitamin D receptor (VDR) in the cells examined. The mechanism of transcriptional regulation of VDR in response to ATRA has not been fully elucidated. Here, we show that the retinoic acid receptor α (RARα) is responsible for regulating VDR transcription in AML cells. We have shown that a VDR transcriptional variant, originating in exon 1a, is regulated by RARα agonists in AML cells. Moreover, in cells with a high basal level of RARα protein, the VDR gene is transcriptionally repressed as long as RARα agonist is absent. In these cells down-regulation of the level of RARα leads to increased expression of VDR. We consider that our findings provide a mechanistic background to explain the different outcomes from treating AML cell lines with a combination of ATRA and 1,25D