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1.
Niger J Clin Pract ; 23(1): 12-17, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31929201

ABSTRACT

BACKGROUND: Until September 1, 2016, Turkey hosted around 2.7 million Syrian refugees. However, data investigating the pregnancy health concerning the refugees are still limited. AIM: In the present study, we aimed to compare the delivery characteristics and short-term obstetric outcomes in Turkish women and Syrian refugees. SUBJECTS AND METHODS: The study included 1556 singleton pregnancies which comprised 940 Turkish women and 616 Syrian women between January 2016 and January 2017. The groups were compared for demographic data, obstetric features, and pregnancy outcomes. RESULTS: There were significant differences between Turkish women and the refugees in terms of preterm (18.94% vs. 11.00%, P = 0.003) and post-term delivery rates (11.49% vs. 2.91%, P < 0.001), caesarian delivery rates (33.4% vs. 23.95%, P = 0.002), newborn weights <1000 g (2.55% vs. 0.97%, P = 0.006) and >4000 g (5.32% vs. 3.24%, P = 0.006), pre-eclampsia (5.32% vs. 1.62%, P = 0.009), HELLP (1.28% vs. 0.00%, P = 0.046), and placental anomalies (1.91% vs. 0.00%, P = 0.014), respectively. Being a Turkish resident (P = 0.015) was an important risk factor for the development of unfavorable pregnancy outcomes. Moreover, maternal education of at least 12 years (P = 0.028) and receiving a regular antenatal visit at a tertiary center (P = 0.031) were preventative for the development of unfavorable pregnancy outcomes. Adverse pregnancy outcomes were less prevalent in Syrian refugees compared to that in the Turkish residents which was likely due to the contribution of maternal education and regular antenatal visits which were higher in Syrian refugees. CONCLUSIONS: We suggest that providing adequate education particularly for women in undeveloped countries and facilitating access to the tertiary hospitals have the potential to reduce unfavorable pregnancy outcomes in immigrant women.


Subject(s)
Cesarean Section/statistics & numerical data , Delivery, Obstetric/statistics & numerical data , Pregnancy Complications/epidemiology , Pregnancy Outcome/ethnology , Refugees/psychology , Refugees/statistics & numerical data , Adult , Birth Weight , Female , Humans , Infant, Newborn , Pregnancy , Premature Birth , Prenatal Care/statistics & numerical data , Retrospective Studies , Risk Factors , Syria/ethnology , Tertiary Care Centers , Turkey/epidemiology , Young Adult
2.
Clin Exp Obstet Gynecol ; 39(3): 288-92, 2012.
Article in English | MEDLINE | ID: mdl-23157026

ABSTRACT

AIM: The aim of the study was to compare maternal and perinatal mortality and short-term outcomes of maternal and perinatal health between a cesarean group with relative indications and a vaginal delivery group. METHODS: A total of 1,119 patients were included; 582 were delivered by spontaneous vaginal birth and 537 delivered by cesarean section without labor. The indication for cesarean section was tocophobia and fear of childbirth for all patients. Maternal and perinatal morbidity and mortality were compared between the groups. RESULTS: No maternal mortality was recorded. Maternal morbidity was significantly lower in the vaginal birth group than the cesarean group (7 vs 30, p<0.05). Perinatal mortality (2 vs 0) and perinatal morbidity were not significantly different between the two groups (33 vs 17). The vaginallly delivered group had significantly higher newborn hospitalization rates than the cesarean group (p<0.05), but hospitalization time did not differ. Newborns with the first minute Apgar score below 7 were higher in the cesarean group (p<0.05). Fifth minute Apgar scores and umblical cord pH values were similiar. Cesarean neonates weighed more than vaginally delivered ones (p<0.05). CONCLUSION: Short-term maternal complications were more frequently seen in cesarean deliveries with relative indications than spontanous vaginal deliveries but no difference was found in perinatal mortality and morbidity. There is a clear need for research on health outcomes for mothers and infants associated with cesarean delivery without any medical indication.


Subject(s)
Cesarean Section/adverse effects , Delivery, Obstetric/adverse effects , Pregnancy Outcome , Adult , Apgar Score , Female , Gestational Age , Hospitalization , Humans , Infant, Newborn , Maternal Mortality , Morbidity , Perinatal Mortality , Pregnancy
3.
Thorac Cardiovasc Surg ; 58(4): 225-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20514578

ABSTRACT

OBJECTIVE: Povidone-iodine (PI) is an effective disinfectant used in many surgical operations. It is known that PI is absorbed by the skin after application. Absorption is even greater in infants, as their skin is thinner and more permeable. Iodine absorption in the orbita, neck and during abdominal surgery has been previously investigated, but such a study has not been performed for the pleura, which has a greater area and capacity for absorption. In this study, we investigated the effect of intraoperative povidone-iodine lavage on thyroid hormones during thoracic surgery. MATERIAL AND METHOD: Fifty patients without any thyroid pathology scheduled for thoracotomy were divided into 2 groups. Group A (n = 25) was given intraoperative saline lavage, while group B (n = 25) had povidone-iodine lavage. Levels of free T3 (FT3), free T4 (FT4) and thyroid-stimulating hormone (TSH) measured 1 day preoperatively and 1 day postoperatively were analyzed. RESULTS: There was a statistically meaningful change in FT3 levels ( P = 0.033) between groups, but the measured changes in FT4 and TSH levels were not statistically significant ( P = 0.98 and P = 0.71, respectively). FT3 scores for group A were decreased postoperatively compared to the scores for group B, but all results were in normal ranges. In group A, the changes between preoperative and postoperative levels of FT3 and FT4 were statistically significant, while changes in TSH levels were not. In group B, changes in FT4 levels were statistically significant and changes in FT3 and TSH levels were not. CONCLUSIONS: The scores show that the iodine absorbed by the pleura during intraoperative povidone-iodine lavage has an effect on thyroid function. Intrapleural PI lavage results in changes to some thyroid hormone levels due to pleural absorption. Thus, intrapleural PI lavage should be used with care.


Subject(s)
Anti-Infective Agents, Local/therapeutic use , Povidone-Iodine/therapeutic use , Therapeutic Irrigation/methods , Thoracotomy , Thyroid Gland/drug effects , Thyroid Hormones/blood , Anti-Infective Agents, Local/adverse effects , Humans , Pleura , Povidone-Iodine/adverse effects , Thyroid Gland/metabolism , Thyrotropin/blood , Thyroxine/blood , Time Factors , Triiodothyronine/blood , Turkey
4.
J Cardiovasc Surg (Torino) ; 47(1): 83-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16434953

ABSTRACT

AIM: Intraoperative frozen section examination (FSE) is an important tool for determining how extensive a surgical procedure needs to be. In this study we reviewed the indications for FSE, the correlation between FSE and postoperative histopathology, and the contribution of intraoperative FSE in determining the extent of the surgical procedure. METHODS: A total of 744 FSE performed in 721 patients between January 1995 and January 2004 were reviewed retrospectively. The FSE were divided into 7 groups according to the indications of the request for frozen section. False positivity and false negativity were evaluated. RESULTS: The indications for FSE included intraoperative diagnosis of pulmonary masses (311, 41.8%), determination of N2 status with mediastinoscopy and mediastinotomy (153, 20.6%), staging of pulmonary carcinomas during the operation (86, 11.6%), assessment of the margin of bronchial surgical resection following pulmonary resection (54, 7.2%), presence of solitary pulmonary nodules (75, 10.1%), presence of mediastinal masses (39, 5.2%), and pleural thickening (26, 3.5%). When compared to postoperative paraffin sections, FSE was found to have a 1.9% (8) rate of false negatives and a 0.2% (1) rate of false positives (P < 0.001). CONCLUSIONS: Intraoperative FSE in thoracic surgery is a rather reliable method. When FSE indicates malignancy, it is a valuable guide in directing the extent of the ongoing surgical procedure. However, when FSE indicates a benign lesion, surgeons should interpret this in the light of the patient's clinical and radiological features and the lesion's macroscopic nature when deciding how extensive an operation needs to be.


Subject(s)
Frozen Sections , Lung Neoplasms/pathology , Thoracic Surgical Procedures , Humans , Intraoperative Period , Lung Diseases/pathology , Mediastinoscopy , Pleura/pathology , Retrospective Studies
5.
Acta Chir Belg ; 106(4): 441-2, 2006.
Article in English | MEDLINE | ID: mdl-17017704

ABSTRACT

A cystic lesion of the liver extending into the inferior vena cava was discovered in a 33-year old female patient suffering from dyspnea, pain and swelling in the legs. Plain chest X-ray was normal. CT and MRI of the thorax showed a cystic lesion within the right pulmonary artery. The liver lesion was treated by a partial cystectomy and omentoplasty, inferior vena cava and bile ducts repair. Through a right thoracotomy, a hydatid cyst was found in the pulmonary artery and enucleated. Although very rare, pulmonary artery hydatidosis may be the cause of an unexplained dyspnea in patients with hydatidosis of the liver.


Subject(s)
Echinococcosis, Hepatic/diagnosis , Echinococcosis/diagnosis , Pulmonary Artery/parasitology , Vascular Diseases/parasitology , Adult , Echinococcosis/surgery , Echinococcosis, Hepatic/surgery , Female , Follow-Up Studies , Humans , Pulmonary Artery/surgery , Vascular Diseases/surgery , Vena Cava, Inferior/parasitology , Vena Cava, Inferior/surgery
6.
Cancer Res ; 49(2): 482-7, 1989 Jan 15.
Article in English | MEDLINE | ID: mdl-2910466

ABSTRACT

The expression of a cell cycle-related nucleolar protein (p145) antigen was examined in the bone marrow aspirates of 45 individuals, three of whom had no malignant disease; 30 had a diagnosis of acute myeloid leukemia (AML), and 12 suffered from chronic myeloid leukemia (CML). While no evidence of p145 expression was found in the three normal bone marrow samples, it was noted to be the highest in patients with active leukemia, be they AML or blastic crisis of CML. There was a direct correlation between the percentage of blasts and the percentage of p145-positive cells in all patients. Double labeling with tritiated thymidine and p145 in AML patients with active leukemia showed that the majority of S-phase cells contained p145. Myeloblasts in both chronic phase and blastic crisis of CML expressed p145. Nine of 12 AML patients studied during remission had less than 5% p145-positive cells, but three showed 11%, 16%, and 33% positive cells. Since functionally/morphologically, these marrows were normal, the appearance of p145 may indicate a proliferative abnormality preceding maturation arrest and development of relapse. Thus we conclude that p145 is more commonly associated with immature cells and may serve as an early indicator of relapse in AML, but requires further study with larger numbers of patients.


Subject(s)
Antigens, Neoplasm/biosynthesis , Bone Marrow/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myeloid, Acute/metabolism , Humans , Interphase
7.
Cancer Res ; 48(21): 5989-94, 1988 Nov 01.
Article in English | MEDLINE | ID: mdl-2844395

ABSTRACT

To assess the changes in the proliferation characteristics that occur during maturation, HL-60 cells were induced to differentiate along the granulocytic pathway by retinoic acid. Differentiation was documented by morphology, functional markers, and cytochemical staining. Durations of S phase, total cell cycle time, and the percentage of S-phase cells were determined simultaneously at each time point. In addition, the expression of two cell cycle related proteins with molecular weights of 110,000 (p110 measured by monoclonal antibody 5C2) and 145,000 (measured by monoclonal antibody p145) were measured to estimate the number of cycling cells or the "growth fraction." Our data demonstrate that as HL-60 cells undergo maturation in response to retinoic acid, a large proportion of cells exit from the cycle, the majority lose their proliferative potential, and the total cell cycle time becomes markedly longer. The slowing of the cell cycle seems to be the result of a prolongation in both S phase and the G1 phase of the cycle. We conclude that more mature myeloid cells cycle more slowly than immature cells. The clinical implications of these findings in myeloid leukemias are discussed.


Subject(s)
Interphase , Leukemia, Promyelocytic, Acute/pathology , Tretinoin/pharmacology , Cell Cycle , Cell Differentiation , DNA/biosynthesis , Humans , Nucleoproteins/analysis , Superoxides/metabolism , Time Factors , Tumor Cells, Cultured
8.
Leukemia ; 10(10): 1648-52, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8847900

ABSTRACT

A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propose that this picture is further complicated by a variety of cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and interleukin 1beta (IL-1beta) which exert a dual effect on the diseased cells. The immature CD34+ cells are stimulated to proliferate, while their later differentiated daughters are induced to undergo apoptosis accounting for the clinical syndrome of pancytopenia despite hypercellular BMs. Studies directed at measuring the rates of proliferation and apoptosis as well as the levels of TNF-alpha, TGF-beta and IL-1beta confirm this hypothesis and are presented in greater detail. A novel approach towards MDS therapy emerges as a result of this paradigm shift based upon the premise that anti-cytokine therapy would prevent excessive intramedullary apoptosis and result in improved cytopenias as well as cause a slowing down of the diseased precursor cell proliferation resulting in resumption of polyclonal hematopoiesis. Because a number of cytokines function through common lipid second messengers, interruption of this pathway should theoretically cause disruption in the signalling of a cascade of cytokines.


Subject(s)
Myelodysplastic Syndromes/pathology , Apoptosis , Bone Marrow/pathology , Cytokines/physiology , Humans , Myelodysplastic Syndromes/etiology
9.
Acta Chir Belg ; 105(2): 221-3, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15906922

ABSTRACT

As the liver and the lungs are the most common sites for hydatid cysts, a primary mediastinal involvement is quite rare. The symptoms related to primary mediastinal hydatid cysts usually depend on the size, location and compression to nearby structures. Presenting a 51-year-old male patient with the symptoms of Horner's Syndrome, we draw attention to a rare complication of a giant primary mediastinal hydatid cyst and its challenging management.


Subject(s)
Echinococcosis/complications , Echinococcosis/diagnosis , Horner Syndrome/etiology , Mediastinal Diseases/complications , Mediastinal Diseases/diagnosis , Albendazole/therapeutic use , Combined Modality Therapy , Echinococcosis/therapy , Follow-Up Studies , Horner Syndrome/physiopathology , Humans , Male , Mediastinal Diseases/therapy , Middle Aged , Risk Assessment , Severity of Illness Index , Thoracotomy/methods , Tomography, X-Ray Computed , Treatment Outcome
10.
Acta Chir Belg ; 105(3): 324-5, 2005.
Article in English | MEDLINE | ID: mdl-16018532

ABSTRACT

Attempts for right and left subclavian vein catheterizations were unsuccessful in a patient followed for pre-eclampsia. Meanwhile, the patient developed chest pain and dyspnea. Chest radiography revealed mediastinal widening. Later, mediastinal haematoma was diagnosed by thoracic computed tomography. At 28 days follow-up, the mediastinal haematoma was resorbed. A review of literature revealed very few cases of mediastinal haematoma secondary to subclavian vein catheterization. In all these cases the haematoma was resorbed, usually within one week. Mediastinal haematoma is a rare complication and its resolution after several weeks adds to its rarity.


Subject(s)
Catheterization, Peripheral/adverse effects , Hematoma/etiology , Mediastinal Diseases/etiology , Subclavian Vein , Adult , Female , Humans , Pre-Eclampsia/therapy , Pregnancy
11.
Exp Hematol ; 20(10): 1194-200, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1426099

ABSTRACT

Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells.


Subject(s)
Cytarabine/metabolism , Cytarabine/therapeutic use , Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/metabolism , Acute Disease , Bone Marrow/metabolism , Bone Marrow/pathology , Bromodeoxyuridine/metabolism , DNA, Neoplasm/metabolism , Dose-Response Relationship, Drug , Humans , Leukemia, Myeloid/pathology , S Phase , Tritium , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/pathology
12.
Exp Hematol ; 25(6): 530-5, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9197332

ABSTRACT

Sixty-eight patients with myelodysplastic syndromes (MDS) received sequential infusions of iodo- and/or bromodeoxyuridine for cell kinetic analysis. Bone marrow biopsy sections were treated by appropriate antibodies and a labeling index (LI), duration of S-phase (Ts), and total cell cycle time (Tc) of myeloid cells were determined. The mean LI was 28.4%, Ts was 11.8 hours and Tc was 40.7 hours. The %LI decreased as the disease evolved from refractory anemia toward transformation to acute leukemia (p = 0.04). Double-labeling of biopsy sections for apoptosis and proliferation showed that 30-90% of S-phase cells in MDS patients were simultaneously apoptotic or "antonymous." We conclude that MDS are highly proliferative disorders in which the ineffective hematopoiesis is probably the result of excessive apoptosis rather than slow proliferation.


Subject(s)
Bromodeoxyuridine , Cell Cycle , Idoxuridine , Myelodysplastic Syndromes/pathology , Apoptosis , DNA/biosynthesis , Humans
13.
Leuk Res ; 13(12): 1055-9, 1989.
Article in English | MEDLINE | ID: mdl-2615464

ABSTRACT

A patient with acute myeloid leukemia received bromodeoxyuridine (BrdU) prior to remission induction therapy. Prior to therapy only leukemic blast cells were found to be labeled. The marrow was aplastic by day 17 with the marrow cavity being devoid of BrdU labeled cells. In contrast rare BrdU containing cells were noted in the paratrabecular and endosteal regions. As the marrow recovered, many regenerating cells contained BrdU, implying that normal stem cells must have been in S-phase at the time of BrdU infusion, and repopulation of marrow may be accounted for by the activity of only a few clones in remission.


Subject(s)
Bone Marrow/physiology , Bromodeoxyuridine/metabolism , Leukemia, Myeloid, Acute/physiopathology , Hematopoiesis , Humans , Interphase , Male , Middle Aged , Regeneration
14.
Leuk Res ; 21(11-12): 1135-9, 1997.
Article in English | MEDLINE | ID: mdl-9444948

ABSTRACT

The incidence of aplastic anemia among hospitalized adult patients was prospectively determined in this first study in Turkey. New cases of aplastic anemia among patients 14 years and older who were admitted to the study centers were included in a 3 year survey. Seventy-three patients fulfilled the diagnostic criteria, yielding a mean annual incidence rate of 1.14 cases in 10(3) admissions. The male-to-female ratio of the cases (1.6:1) differed from the almost equal ratio of the larger population of Turkey. The median age was 30 years and females were younger at diagnosis. The age distribution of the cases was different from that of the population; showing two incidence peaks in both sexes. The majority of the patients (89%) had severe disease.


Subject(s)
Anemia, Aplastic/epidemiology , Adolescent , Adult , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Turkey
15.
Leuk Res ; 24(8): 671-80, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10936421

ABSTRACT

Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Adult , Aged , Aged, 80 and over , Amifostine/administration & dosage , Cytarabine/administration & dosage , Humans , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/physiopathology , Middle Aged , Mitoxantrone/administration & dosage , Pilot Projects , Prognosis , Radiation-Protective Agents/administration & dosage , Treatment Outcome
16.
Leuk Res ; 23(4): 357-64, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10229321

ABSTRACT

Rates of proliferation and apoptosis as well as expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and the number of macrophages were measured in bone marrow (BM) biopsies of 33 patients who presented with hypocellular (cellularity < 30%) myelodysplastic syndromes (MDS). Results showed that 2/3 of the patients had high apoptosis, high cytokine levels and large number of macrophages in their biopsies while 1/3 did not. Apoptosis and TNF-alpha levels were directly related (r = 0.583, P = 0.003, n = 24) as was apoptosis and the degree of anemia (P = 0.033, n = 18). A subgroup of patients with abnormalities of chromosomes 5 or 7 had higher platelets (P = 0.026) and higher apoptosis (P = 0.038) when compared with the rest of the group. Eight patients had no evidence of apoptosis and almost no detectable TNF-alpha in their biopsies. We conclude that within the hypocellular variant of MDS, there may be two distinct sub-groups of patients, one who present with high cytokine-mediated intramedullary apoptosis and the other who may be better characterized as having a stem-cell failure defect since they showed no evidence of apoptosis.


Subject(s)
Myelodysplastic Syndromes/pathology , Adolescent , Aged , Aged, 80 and over , Apoptosis , Cytokines/metabolism , Female , Hematopoietic Stem Cells/pathology , Humans , In Situ Nick-End Labeling , Karyotyping , Macrophages/pathology , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , S Phase
17.
Leuk Res ; 25(11): 941-54, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11597729

ABSTRACT

We used bone marrow biopsies instead of mononuclear cells to maintain long-term cultures from 103 patients belonging to all five sub-categories of myelodysplastic syndromes (MDS), as well as 12 normal controls. By week 4, 30-50% confluency was reached and could be maintained for up to 12 weeks with 100% confluency. The four prominent cells were fibroblasts, macrophages, endothelial cells and adipocytes. Immunohistochemical and electron microscopic studies provided lineage confirmation. Normal hematopoiesis was well supported by MDS stroma. Neither the FAB nor cytogenetics was co-related with the potency of growth. MDS stroma appears to be both morphologically and functionally normal.


Subject(s)
Bone Marrow Cells/cytology , Myelodysplastic Syndromes/pathology , Adipocytes/cytology , Adult , Aged , Aged, 80 and over , Antigens, CD34/blood , Bone Marrow Cells/ultrastructure , Case-Control Studies , Cell Culture Techniques/methods , Cell Division , Cell Lineage , Coculture Techniques , Cytogenetic Analysis , Endothelium/cytology , Fetal Blood/immunology , Fibroblasts/cytology , Hematopoiesis , Humans , Immunohistochemistry , Macrophages/cytology , Microscopy, Electron , Middle Aged , Myelodysplastic Syndromes/classification , Stromal Cells/cytology
18.
Leuk Res ; 20(11-12): 891-900, 1996.
Article in English | MEDLINE | ID: mdl-9009245

ABSTRACT

Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-alpha and TGF-beta in 41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-alpha and the incidence of PCD (p= 0.0015). Patients who showed high PCD also had an elevated TNF-alpha level. Thus, the expression of high amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline.


Subject(s)
Apoptosis , Bone Marrow/chemistry , Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Myelodysplastic Syndromes/pathology , Transforming Growth Factor beta/analysis , Tumor Necrosis Factor-alpha/analysis , Bone Marrow/pathology , Cell Division , Cell Lineage , Connective Tissue/pathology , DNA Fragmentation , Female , Hematopoiesis/physiology , Hematopoietic Stem Cells/pathology , Humans , Macrophages/pathology , Male , Myelodysplastic Syndromes/etiology , Myelodysplastic Syndromes/metabolism
19.
Int J Hematol ; 63(4): 265-78, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8762810

ABSTRACT

The paradox of myelodysplastic syndromes (MDS) which present with pancytopenias despite cellular bone marrows (BM) was investigated by conducting detailed studies of proliferation and apoptosis in 89 MDS patients. Our results demonstrated a rapid rate of both proliferation as well as apoptosis. Levels of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta) were measured in the same patients. High levels of TNF-alpha were found to correlate with high levels of apoptosis in 83 MDS patients (P = 0.0045). We propose a dual role for TNF-alpha (or other cytokines) in the pathogenesis of MDS. On the one hand, TNF-alpha induces apoptosis in the maturing cells causing pancytopenia while on the other, it stimulates the proliferation of the primitive progenitors accounting for the hypercellular BM frequently seen in MDS. A new model for MDS is presented. The initial abnormality probably affects a primitive hemopoietic progenitor which acquires a growth advantage leading to monoclonal hemopoiesis, which in turn makes these cells susceptible towards acquiring additional mutations and appearance of cytogenetically marked (or unmarked) clones. Cytokines such as TNF-alpha whose source is presently unknown, then contribute towards the clinical syndrome of pancytopenia and hypercellularity.


Subject(s)
Apoptosis , Cytokines/physiology , Hematopoietic Stem Cells/pathology , Myelodysplastic Syndromes/physiopathology , Antigens, CD34/analysis , Bone Marrow/pathology , Cell Division , DNA Replication , Disease Progression , Humans , Interleukin-1/blood , Interleukin-1/physiology , Leukemia/etiology , Models, Biological , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/pathology , Transforming Growth Factor beta/blood , Transforming Growth Factor beta/physiology , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/physiology
20.
Cancer Genet Cytogenet ; 79(1): 86-8, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7850760

ABSTRACT

This study was made to show the effects of acute leukemia (AL) and cytostatic drug therapy on chromosomes by sister chromatid exchange (SCE) analysis. Metaphase preparations from peripheral blood lymphocytes (PBL) of 15 patients [13 with acute nonlymphocytic leukemia (ANLL) and one with acute lymphocytic leukemia (ALL), and one with Hodgkin's disease (HD)] were harvested before and after treatment. Mean SCE frequency in the cells was 12.07 +/- 0.15 before therapy and was 14.04 +/- 0.32 after therapy as compared with 7.87 +/- 0.60 in controls. SCE values of patients with AL were significantly higher than those of controls, and this was more conspicuous in the cells that had undergone anticancer treatment.


Subject(s)
Leukemia/genetics , Sister Chromatid Exchange/genetics , Acute Disease , Adult , Female , Humans , Male , Middle Aged
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