Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
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.
Thorac Cardiovasc Surg ; 56(4): 221-5, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18481242

ABSTRACT

BACKGROUND: Completion pneumonectomy performed for benign causes is associated with a high morbidity and mortality. We analyzed the patients who underwent completion pneumonectomy procedure for bronchiectasis, which constitutes a specific benign condition, together with the indications for surgery, the difficulties encountered during operations and the postoperative results. METHODS: Records of all patients who underwent completion pneumonectomy for the diagnosis of brochiectasis between January 1991 and April 2006 at the thoracic surgery clinic of a training and research hospital specializing in chest diseases and chest surgery were retrospectively evaluated. The age and the gender of the patients, etiologic factors, symptoms, characteristics of the first operation, the time between the first operation and completion pneumonectomy, and postoperative follow-up are examined. RESULTS: During the evaluation period of more than 15 years, 23 patients underwent completion pneumonectomy. The median age of these 23 patients was 28 (range: 9 - 53); 17 of the patients were male and 6 were female. The most common indication for surgery was recurrent lung infections (n = 15). The most common symptoms were cough (n = 21), expectoration (n = 19), and hemoptysis (n = 15). The mean time between the first operation and the completion pneumonectomy was 4.9 years (range: 5 months - 11 years). Left completion pneumonectomy was performed in 14 and right completion pneumonectomy was performed in 9 cases. The mean duration of hospital stay was 16.7 days (range: 12 - 42 days). The course after surgery was uneventful in all patients. The mortality rate was 0 % and morbidity was 43.5 %. CONCLUSION: Although completion pneumonectomy for benign causes is a high risk procedure, it can be performed in selected patients with an acceptable morbidity and mortality after an effective preoperative medical therapy for inflammation of the lungs and with careful dissection at the operation.


Subject(s)
Bronchiectasis/surgery , Pneumonectomy/methods , Adolescent , Adult , Bronchiectasis/diagnostic imaging , Bronchiectasis/embryology , Bronchiectasis/mortality , Child , Comorbidity , Female , Humans , Lung Diseases/epidemiology , Male , Middle Aged , Pneumonectomy/adverse effects , Pneumonectomy/mortality , Postoperative Complications/epidemiology , Pulmonary Veins/surgery , Tomography, X-Ray Computed
5.
Thorac Cardiovasc Surg ; 55(7): 462-3, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17902072

ABSTRACT

Pulmonary arteriovenous malformations are abnormal communications between pulmonary arteries and pulmonary veins. The majority of the cases are congenital in origin, and acquired pulmonary arteriovenous malformations are very rare. We present a case here, which - to the best of our knowledge - is the first acquired pulmonary arteriovenous malformation secondary to a hydatid cyst operation in the literature, and we discuss the etiology, clinical presentation, diagnostic modalities and treatment of acquired pulmonary arteriovenous malformations.


Subject(s)
Echinococcosis, Pulmonary/surgery , Hemoptysis/etiology , Pulmonary Artery/injuries , Pulmonary Surgical Procedures/adverse effects , Pulmonary Veins/injuries , Wounds and Injuries/etiology , Adult , Hemoptysis/pathology , Hemoptysis/surgery , Humans , Male , Pulmonary Artery/pathology , Pulmonary Veins/pathology , Treatment Outcome , Wounds and Injuries/complications , Wounds and Injuries/pathology , Wounds and Injuries/surgery
6.
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
7.
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
8.
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
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.
Leuk Lymphoma ; 45(10): 2099-104, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15370256

ABSTRACT

Remicade, a chimeric human-murine monoclonal antibody capable of neutralizing tumor necrosis factor alpha was given to 37 low-risk myelodysplastic syndromes (MDS) patients in two cohorts; 5 and 10 mg/kg intravenously every 4 weeks for 4 cycles. Median age was 68 years, 33 had primary MDS, 14 had refractory anemia (RA), 14 RA with ringed sideroblasts, 9 RA with excess blasts. Nine patients stopped therapy prior to completing 4 cycles, 3 from cohort 1 and 6 from cohort 2 and response was evaluated using the International Working Group criteria in 28 patients who completed the 4 cycles. Six patients showed disease progression, 14 had stable disease and 8 showed hematologic responses, 3/15 (20%) in cohort 1 and 5/13 (38%) in cohort 2. Two patients had multi-lineage responses, 2 had > 100% increase in absolute neutrophils, 1 had > 1 gm/dl increase in hemoglobin, 1 had reduction in blasts from 7% to 1%, and 2 had minor cytogenetic responses (> 50% reduction in + 8 and 20q-metaphases respectively). We conclude that Remicade may have a variety of activities in low risk MDS patients, is well tolerated with a high patient compliance, and may be considered for combination therapy in the future.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Myelodysplastic Syndromes/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Aged , Anemia, Refractory , Antibodies, Monoclonal/toxicity , Chromosome Aberrations , Cytogenetic Analysis , Disease Progression , Female , Humans , Infliximab , Male , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Pancytopenia/drug therapy , Patient Compliance , Pilot Projects , Remission Induction , Treatment Outcome
11.
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
12.
Blood ; 98(4): 958-65, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11493439

ABSTRACT

Thalidomide was administered to 83 patients with myelodysplastic syndrome (MDS), starting at 100 mg by mouth daily and increasing to 400 mg as tolerated. Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy. International Working Group response criteria for MDS were used to evaluate responses. Intent-to-treat (ITT) analysis classified all off-study patients as nonresponders. Off-study patients belonged to a higher risk category (P =.002) and had a higher percentage of blasts in their pretherapy bone marrow than patients who completed 12 weeks of therapy (P =.003). No cytogenetic or complete responses were seen, but 16 patients showed hematologic improvement, with 10 previously transfusion-dependent patients becoming transfusion independent. Responders had lower pretherapy blasts (P =.016), a lower duration of pretherapy platelet transfusions (P =.013), and higher pretherapy platelets (P =.003). Among responders, 9 had refractory anemia (RA); 5 had RA with ringed sideroblasts; and 2 had RA with excess blasts. By ITT analysis, 19% of patients (16 of 83) responded, and when only evaluable patients were analyzed, 31% (16 of 51) responded. It was concluded that thalidomide, as a single agent, is effective in improving cytopenias of some MDS patients, especially those who present without excess blasts. (Blood. 2001;98:958-965)


Subject(s)
Anemia/drug therapy , Blood Transfusion , Myelodysplastic Syndromes/drug therapy , Thalidomide/pharmacology , Aged , Anemia/blood , Anemia/etiology , Blood Cell Count , Bone Marrow/drug effects , Bone Marrow/pathology , Female , Hematopoiesis/drug effects , Hemoglobins/metabolism , Humans , Male , Maximum Tolerated Dose , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/complications , Pilot Projects , Thalidomide/toxicity , Treatment Outcome
13.
Leuk Lymphoma ; 41(3-4): 333-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11378545

ABSTRACT

Twenty five patients with AML who had neither a history of toxic exposure or myelodysplasia were treated with a remission induction regimen consisting of two pulses of chemotherapy separated by 96 hrs. Each pulse consisted of cytarabine 2gm/m(2) (at t=0 and t=12 hrs) with mitoxantrone [30mg/m(2) ] administered immediately after the second cytarabine administration. Amifostine was administered three times a week [on Monday, Wednesday, and Friday] until the outcome of therapy was known. This regimen induced complete remissions in 15 of 17 patients less than 70 years of age and in 5 of 8 patients older than 70 years.


Subject(s)
Antineoplastic Agents/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/standards , Cohort Studies , Cytarabine/administration & dosage , Cytarabine/standards , Cytogenetic Analysis , Drug Administration Schedule , Humans , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/genetics , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/standards , Remission Induction , Time Factors , Treatment Outcome
14.
Eur Urol ; 39(3): 292-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11275722

ABSTRACT

OBJECTIVE: Elastase is a serine protease which hydrolyses connective tissue components. Laminin and fibronectin also play an important role in progression and invasion of cancer. The purpose of this study is to investigate the relation between tissue elastase, laminin P(1) and fibronectin levels and tumor characteristics, and analyze the potential of these as prognostic factors in transitional cell carcinoma (TCC) of the bladder. METHODS: Thirty-four patients with TCC of the bladder and 11 controls were included in this study. Elastase and fibronectin levels in tissue homogenates were determined using an enzyme immunoassay and laminin P(1) by radioimmunoassay. Mean follow-up was 43 months. RESULTS: The mean elastase level in bladder carcinoma tissue was 120+/-11.42 ng/homogenate protein, while normal tissue level was 12.36+/-2.70 (p<0.01). The carcinoma and normal tissue mean laminin P(1) levels were 7.02+/-0.37 U and 0.65+/-0.10 U/mg homogenate protein, respectively (p<0.01). The mean fibronectin level was 19.97+/-1.45 ng/mg homogenate protein in the carcinoma tissue and 2.16+/-0.40 in normal tissue (p<0.01). There was no correlation between tumor stage, grade, size, multiplicity and elastase, laminin P(1) and fibronectin levels. CONCLUSION: These results provide evidence that tissue elastase, laminin P(1) and fibronectin levels increase in TCC of the human bladder. Further studies including serum and urine levels should be performed in order to analyze their value as tumor markers in a larger group of patients.


Subject(s)
Carcinoma, Transitional Cell/chemistry , Fibronectins/analysis , Laminin/analysis , Pancreatic Elastase/analysis , Peptide Fragments/analysis , Urinary Bladder Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis
15.
Neurotox Res ; 3(3): 277-80, 2001 Jul.
Article in English | MEDLINE | ID: mdl-15111252

ABSTRACT

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. The hypothesis that methamphetamine-induced neurotoxicity is mediated by reactive oxygen species was evaluated. It was found that acute administration of methamphetamine (5 and 15 mg kg(-1)) resulted in production of oxidative stress as demonstrated by decreased glutathione and increased oxidized glutathione levels in the rat striatum and prefrontal cortex. These changes in glutathione and oxidized glutathione levels were dose-dependent in striatum but not in prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

16.
Br J Haematol ; 115(4): 881-94, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11843822

ABSTRACT

Thirty patients with myelodysplastic syndromes (MDS) were treated with thalidomide at 100 mg/d p.o., increased as tolerated to 400 mg/d for 12 weeks. Levels of apoptosis, macrophage number, microvessel density (MVD), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined in the serum, bone marrow (BM) plasma and BM biopsies before and after therapy. Pretherapy biological characteristics of MDS patients were compared with similar studies performed in 11 normal volunteers. Ten patients demonstrated haematological improvement in the erythroid series, six becoming transfusion independent. Responders had a higher pretherapy platelet count (P < 0.048) and lower BM blasts (P < 0.013). Median time to response was 10 weeks, and four remain in remission beyond a year. Pretherapy MDS BMs showed higher MVD (P < 0.001) and TGF-beta (P < 0.03) and higher serum TNF-alpha (P < 0.008) compared with normal control subjects. After therapy, only BM TGF-beta decreased significantly (P < 0.002). Pretherapy haemoglobin was directly related to serum VEGF (P < 0.001) in responders and inversely related in non-responders (P < 0.05), suggesting the possibility that angiogenesis may be a primary pathology in the former and a consequence of anaemia-induced hypoxia in the latter. We conclude that thalidomide has important clinical and biological effects in at least a subset of MDS patients, but the precise mechanism of its action remains unknown and requires further study including a larger number of patients.


Subject(s)
Cytokines/analysis , Immunosuppressive Agents/therapeutic use , Myelodysplastic Syndromes/drug therapy , Thalidomide/therapeutic use , Aged , Case-Control Studies , Cytokines/blood , Endothelial Growth Factors/blood , Female , Hemoglobins/analysis , Humans , Lymphokines/blood , Male , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/immunology , Platelet Count , Remission Induction , Transforming Growth Factor alpha/blood , Transforming Growth Factor beta/analysis , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
17.
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
18.
Blood ; 95(5): 1580-7, 2000 Mar 01.
Article in English | MEDLINE | ID: mdl-10688811

ABSTRACT

Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M(2), 300 mg/M(2), and 400 mg/M(2)) to cohorts of 10 patients each. Therapy has been continued for 1 year in responders. Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secondary MDS. No differences were noted in response rates among the 3 dose levels. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%). Three had a triple lineage response, 10 had a double lineage response, and 9 had a single lineage response (8 of 9 in absolute neutrophil count [ANC] and 1 had more than a 50% reduction in packed red blood cell transfusions). Fifteen patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in blood transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond. This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered. (Blood. 2000;95:1580-1587)


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Myelodysplastic Syndromes/drug therapy , Palliative Care , Adult , Aged , Aged, 80 and over , Amifostine/administration & dosage , Amifostine/adverse effects , Anorexia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Blood Cell Count/drug effects , Ciprofloxacin/administration & dosage , Ciprofloxacin/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Female , Gastrointestinal Diseases/chemically induced , Hematologic Diseases/chemically induced , Humans , Hypotension/chemically induced , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Pentoxifylline/administration & dosage , Pentoxifylline/adverse effects , Treatment Outcome
19.
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
20.
Eur J Haematol ; 62(2): 90-4, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10052711

ABSTRACT

Spontaneous intramedullary apoptosis was measured in bone marrow (BM) biopsies of 175 patients with myelodysplastic syndromes (MDS) using in situ end-labeling (ISEL) of fragmented DNA. Two groups of high (n=71) versus low (n =43) levels of apoptosis were identified while 61 patients were ISEL-negative. Semiquantitative assessment of 3 cytokines, the number of macrophages and in vivo labeling indices (LI) were also determined from consecutive sections of the biopsy. Patients with high apoptosis levels tended to have a high LI (p=0.013), more macrophages in their BM biopsies (p=0.006) and higher tumor necrosis factor alpha (TNF-alpha) levels (not significant) compared to patients with no apoptosis. In addition, low risk MDS patients had significantly lower rates of apoptosis (p = 0.047) and lower levels of TNF-alpha (p = 0.055) compared to high-risk MDS patients. We conclude that the genesis of cytopenias in MDS is of multifactorial origin and that cytokine-associated apoptosis clearly identifies a distinct biological subgroup of patients who may benefit selectively by use of anti-cytokine therapies.


Subject(s)
Apoptosis , Bone Marrow/pathology , Myelodysplastic Syndromes/pathology , Tumor Necrosis Factor-alpha/metabolism , Aged , Biomarkers , Female , Humans , Male , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/physiopathology
SELECTION OF CITATIONS
SEARCH DETAIL
...