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The role of CYFRA 21-1, nucleosome and neurone-specific enolase as
early measures of chemotherapy response in non-small cell lung
cancer
Mohamed A. Alm El-Din, M.D.,* Ayman Abd El-Zaher, M.D.,§ Hala Nagy, M.D.,‡
Gihan Farouk, M.D.,‡ Gehan H. Abo El-Magd, M.D. §
Departments of Clinical Oncology, * Clinical Pathology, ‡ and Chest §
Tanta Faculty of Medicine, Tanta, Egypt
Abstract:
Background: To investigate the decline in the level of cytokeratin-19 fragments
(CYFRA 21-1), nucleosomes and Neurone specific enolase (NSE) as an early
indication of response to chemotherapy in lung cancer.
Methods: Forty-two consecutive patients with locally advanced non-small cell lung
cancer were included. All patients received platinum-based chemotherapy. Staging
investigations and assay of CYFRA 21-1, nucleosomes and NSE using enzyme linked
immunosorbent assay (ELISA) were done before the start of treatment and after the
second cycle of chemotherapy. According to response to chemotherapy, patients were
classified into three groups: regressive disease (group I), stable disease (group II) and
progressive disease (group III). The decline of tumour markers was correlated to the
response to chemotherapy.
Results: After the second dose of chemotherapy, Group I and II had significant
decrease in the level of CYFRA 21-1 (P < 0.05). Also, the concentration of
nucleosomes was significantly lower as compared to the baseline level in group I and
II (P 0.0008 and 0.003, respectively). The decline in both CYFRA 21-1 and
nucleosomes was not significant for patients with progressive disease (group III). The
level of NSE showed insignificant decline in response to chemotherapy in all groups.
As an indication for response to chemotherapy, CYFRA 21-1 showed the highest
sensitivity and specificity compared to nucleosomes and NSE (88.9, 77.4 vs. 77.8,
58.1 and 66.7, 51.8, respectively).
Conclusion: The decline in the serum level of CYFRA 21–1 and nucleosomes may
be used in early identification of patients with good response to chemotherapy.
The relationships between CD14 and CC16 genotypes, plasma levels,
& severity in acute asthma patients
Ayman H. Abd El-Zaher1, Heba Mourad 2, Amal EL-Bandary 2,
Hala M. Nagy 2, and Waleed Samy 3
Departments of Chest1, Clinical Pathology 2 and Internal Medicine 3
Faculty of Medicine, Tanta University, Egypt
Abstract:
Background: Acute asthma is characterized by acute episodes of obstruction
related to airway inflammation mostly in response to respiratory tract infection. CD14
and Clara cell protein (CC16) play a key role in inflammatory pathways.
Objective: The aim of this study is to determine the influence of CD14 and CC16
gene polymorphism and plasma levels of their products on the predisposition to
develop asthma and its severity.
Methods: This study was conducted on 40 patients during acute attack of asthma
(group I) and in convalescence (after 6 weeks of treatment of the same patients, group
II). Asthma severity scoring system was preformed to all patients according to
(Martin et al; 2006). Arterial blood gases, plasma levels of sCD14, CC16 and serum
total IgE were measured by ELISA. CD14 and CC16 gene polymorphism were
detected by restriction fragment polymorphism (RFLP).
Results: During acute asthma, plasma level of sCD14 and CC16 were significantly
higher than during convalescence: sCD14, 3.23±0.48 versus 2.64±0.24 µg/ml, (p=
0.001); CC16, 2.52±0.33/m versus 1.76±0.22 µg/ml, (p= 0.002). Higher plasma levels
of sCD14 were present during the acute attack in those with 159TT and 159TC (p=
0.002 & p= 0.001, respectively), whereas in 159CC homozygous, sCD14 levels were
insignificantly increase during the acute attacks (p= 0.119). Also higher plasma levels
of CC16 were present during the acute attack in those with 38GG and 38AG (p=
0.001 & p=0.002, respectively), whereas in 38AA homozygous, CC16 levels were
actually lower during the acute attacks than during convalescence, although this
difference was not statistically significant (p= 0.093). A significant negative
correlation was found between sCD14 and asthma score (r= 00.58, p= 0.001), while a
insignificant positive correlation was found between CC16 and asthma score (r=
0.0243, p= 0.13). There was a significant positive correlation between IgE and plasma
level of sCD14, CC16 and asthma score.
Conclusion: These results suggest that in acute asthma production of both sCD14
and CC16 is increased in an attempt to control airway inflammation, and for subjects
whose genotype limits or prevents these increases, the ability to control airway
inflammation is impaired resulting in more severe asthma. Therefore, this study
supports the concept that sequence variations in the CD14, CC16 gene are likely to
play a role in the development of asthma.
Effect of a disintegrin and metalloprotease 33 (ADAM33) gene
polymorphisms & smoking in COPD
Ayman H. Abd El-Zaher*, Hala Nagy**, Gihan Farouk**, Ahmed Sh. Mohamed*
& Naglaa F. Ghoname***
Departments of Chest*, Clinical Pathology** and Microbiology & Immunology***
Faculty of Medicine, Tanta University, Egypt
Abstract:
Background: COPD is characterized by air flow limitation that is not fully
reversed and associated with an influx of neutrophils, macrophages and CD8 T
lymphocytes in the airways. The disease is characterized by airflow limitation and is
associated with an abnormal inflammatory response of the lungs in response to
noxious particles or gases and associated with systemic manifestation.
Methods: 60 consecutive patients with COPD and 40 normal healthy individuals
were included. All cases and controls were subjected to detection of 2 polymorphic
loci (S1 AND Q1) of ADAM33 by PCR-RFLP technique.
Results: The percentage of S1 and Q1 AA genotype and A allele were significantly
increased in control than in COPD patients while there was significant increase in S1
and Q1 GG genotype and G allele in COPD patients than in control (p<0.001). no
significant difference was found between smoker and non-smoker among the two
studied groups in genotype and alleles distribution of ADAM33 SNPs S1 and Q1
p>0.05, whereas there was significant increase in ADAM33 S1 G allele and Q1 G
allele in smoker and non-smoker in COPD patients as compared to their
corresponding fellows in control group ( p<0.05). As regard to Pulmonary function
test there was significant decrease in % of FEV1 in COPD patients as compared to
control group for both smokers and non-smokers (p<0.001). Within both control and
COPD groups smokers had significant decrease in FEV1% as compared to nonsmokers (p<0.001). There was a significant decrease in FEV1% among all genotypes
in smoker as compared to non-smoker COPD patients (p<0.001), the most prominent
decrease was found in smoker GG genotype for both ADAM33 S1 and Q1 in COPD
patients.
Conclusion: We found that polymorphisms in the SNPs (Q1 and S1) of ADAM33
gene are associated with COPD in the general population. In addition, smoker patients
with GG genotype in (S1 and Q1) ADAM33 will have more pronounced decline in
the pulmonary function test (FEV1).
Diagnostic utility of sonar guided biopsy in tuberculous effusion
Ayman Abd El-Zaher1, Ibrahim Salah1, Mohamed Hantera1, Radwa
Oreby2, Ebrahim Abaas3
Departments of Chest1, Pathology2 & Radiology, Faculty of Medicine, Tanta University, Egypt
ABSTRACT
Background /Aim: Tuberculous pleural effusion remains the commonest cause of
exudative effusions in areas with a high prevalence of tuberculosis and histological
examination of pleural tissue is the gold standard for its diagnosis. This study was to
assess the dialogistic utility of sonar guided biopsy in tuberculous pleural effusion.
Patients & Methods: 50 patients (34 men) of mean ± SD age 38.7±16.7 years
with pleural effusions and a clinical suspicion of tuberculosis were enrolled in the
study. Transthoracic ultrasound was performed on all patients, who were then
randomly assigned to undergo ≥4 Abrams needle biopsies followed by ≥4 Tru-Cut
needle biopsies or vice versa. Medical thoracoscopy was performed on cases with
non-diagnostic closed biopsies.
Results: Pleural tuberculosis was diagnosed in 31 patients, alternative diagnoses
were established in 16 patients and 3 remained undiagnosed. Pleural biopsy
specimens obtained with Abrams needles contained pleural tissue in 29 patients
(92.0%) and were diagnostic for tuberculosis in 26 patients (sensitivity 82%),
whereas Tru-Cut needle biopsy specimens only contained pleural tissue in 21 patients
(78%) and were diagnostic in 21 patients (sensitivity 64%).
Conclusions: Ultrasound-assisted pleural biopsies performed with an Abrams
needle are more likely to contain pleura and have a significantly higher diagnostic
sensitivity for pleural tuberculosis.
Effect of obstructive sleep apnea syndrome on left ventricular
function
Mohamed G. El-Kholly*, Medhat M Ashmawy**, Ayman H Abd EL-Zaher* &
Mahmoud EL-Shahat*
Departments of Chest* & Cardiology**, Faculty of Medicine, Tanta University, Egypt
Abstract
Background: The link between OSAS, left ventricular dysfunction, and congestive
heart failure is less known, although OSAS is frequent in both systolic and diastolic
heart failure patients.
Aim: To study left ventricular function in patients with obstructive sleep apnea
syndrome & to assess the correlation between the severity of OSA and the degree of
ventricular dysfunction.
Subjects and Methods: This study was conducted on 45 subjects (22 males & 23
females) in Chest Department, Tanta University Hospitals, they were classified into 2
groups: Group A included 15 apparently healthy subjects, by sleep study they were
normal as apnea hypopnea index (AHI) < 5/h and oxygen desaturation index (ODI) <
5/h. Group B included 30 patients with obstructive sleep apnea diagnosed by sleep
study (AHI > 5/h & ODI > 5/h).
Results: Eight (26.66%) out of the 30 OSAS patients (group B) were hypertensive
and have left ventricular dysfunction. The mean value of AHI was (2.53±1.06) and
(24.6±14.35) in group A and B respectively. The mean value of AHI was significantly
higher in group B than group A (p = 0.001). Significant correlation was found
between AHI, diastolic and systolic dysfunction respectively (r= 0.324; p= 0.019 and
r=0.288; p=0.049) (figure 2, 3).
Conclusion: Obstructive sleep apnea syndrome may predispose in left ventricular
diastolic dysfunction, AHI is correlated with the degree of left ventricular diastolic
dysfunction.
Soluble triggering receptor expressed on myeloid cells -1 as
differential biomarker of pleural effusion
Ayman H. Abd El-Zaher*, Ali M. Abd-Ella*, Hala Nagy** & Raba Y. Talab*
Departments of Chest* & Clinical Pathology** Faculty of Medicine, Tanta University, Egypt
Abstract
Background & Objective: The currently available diagnostic markers for
pleural effusion have a limited role. The soluble triggering receptor expressed on
myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role
in the myeloid cell mediated inflammatory response, and is up regulated in the body
fluid by bacterial or fungal products. This study aimed to investigate the value and
significances of sTREM-1 in the diagnosis of pleural effusion caused by different
diseases entities.
Methods: Samples of pleural fluid from 50 patients, (10 with empyema, 10 with
para-pneumonic effusions, 10 with tuberculous effusion, 10 with malignant effusion
and 10 with transudative effusion). Patients were assessed for the level of sTREM-1
by ELISA in pleural fluid. Total and differential cell count, LDH, glucose and protein
were carried out to all studied patients.
Results: Level of sTREM-1 was highest in empyema, followed by infectious
exudates and the level of sTREM-1 were low in transudate and non-infectious
exudates and there was positive correlation between sTREM-1 and (protein, total
white blood cells and neutrophil % in pleural fluid) and serum LDH and negative
correlation between sTREM-1 and lymphocyte % in pleural fluid.
Conclusions: Our findings suggest a role for sTREM-1 in differentiation between
infectious and non infectious pleural effusion.
Medical thoracoscopy using fiberoptic broncoscopy
Ayman Abd El-Zaher1, Mohamed Hantera1, Alaa Metwaly2 Dina Radi3
Departments of Chest, Tanta1 & Zakazeek Universities2 & Pathology Department3 Tanta University
Abstract
Background, Aim: Undiagnosed exudative pleural effusion remains a matter of
interest in both clinical and research fields in chest practice. The evolution in methods
of diagnosis started by Abrams closed biopsy then sonar guided closed biopsy then
rigid thoracoscopy and lastly semi-rigid thoracoscopy and VATS, but what about
centers without these facilities. The aim of this study is to assess the ability of
fiberoptic broncoscopy through chest tube to replace rigid broncoscopy in diagnosis
of undiagnosed exudative effusion.
Patients and method: 20 patients with undiagnosed exudative pleural effusion
were examined by fiberoptic broncoscopy through chest tube under local anaesthesia
and biopsies were taken by forceps through working channels of broncoscopy.
Results: Definite diagnosis established in 16 patients and 4 patients undiagnosed
due to insufficient material, with no complications.
Conclusions: Medical thoracoscopy using fiberoptic broncoscopy is safe
manoeuvre and can replace rigid thoracoscopy in centers which cannot have.
Assessment of sleep apnea in patients with liver cirrhosis
Raafat A. Salah * & Ayman H Abd El Zaher **
Departments of Tropical * & Chest **, Faculty of Medicine, Tanta University, Egypt
Abstract
Objective: Patients with obstructive sleep apnea (OSA) are at risk for the
development of fatty liver as a result being overweight. Several data suggest that OSA
per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been
reported. Obstructive sleep apnea has been reported to be a new complication of liver
cirrhosis with ascites. Therefore we investigated the episodes of sleep apnea as a
complication of advanced liver cirrhosis.
Methods: Sixty patients with liver cirrhosis due to chronic hepatitis C were divided
according to the child-pugh score into 3 groups: Group A (20 patients grade A
cirrhosis), Group B (20 patients grade B cirrhosis), and Group C (20 patients grade C
cirrhosis). Portable sleep polygraph (ResMed corp., CA, USA) were attached to the
subjects, and oronasal respiration, tracheal sounds, Respiratory movements of the
chest, and percutenaous arterial oxygen saturation continuously were recorded. A
decrease in the mean airflow to 50% or less was defined as hypopnea, and the number
per hour of episodes of apnea and hypopnea per hour lasting 10 seconds or longer
(AHI) was counted.
Results: AHI was Results: AHI was significantly higher in Group C than in Groups
A and B (p<0.05). In Group C, 6 patients with 20 times or more AHI per hour,
obstructive sleep apnea, in which respiratory chest movements occur but oronasal
respiration decreases or disappears, was observed.
Conclusions: As the stage of liver cirrhosis advanced, sleep apnea appeared, and
changes in autonomic nervous activities were observed.
Role of granulocyte-colony stimulating factor in patients with
idiopathic pulmonary fibrosis
Waffa S. Al-Shimy*; Amgad A. Farhat*; Ayman H. Abd El-Zaher*; Hala M.
Nagy**; Ghada A. Attia* & Ahmed M. Gamal Eldeen*
Departments of Chest* & Clinical Pathology**, Faculty of Medicine, Tanta University, Egypt
Abstract
Background & objective: Idiopathic pulmonary fibrosis (IPF) is progressive
lung disease with an associated mean survival 3-5 years. Granulocyte-colony
stimulating factor (G-CSF) is known as a potent neutrophil chemotactic glycoprotein
but its contribution to chemotactic activity in neutrophil mediated lung diseases is not
yet known. The aim of this study was to determine level of G-CSF in bronchoalveolar
lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis and to correlate its
level with neutrophil count in BAL fluid and the severity of the disease.
Methods: the study was conducted on 40 subjects who classified into two groups;
10 healthy non-smokers subjects (control group) & 30 non-smokers IPF (patients
group). BAL analysis was done for measurement of neutrophil count and G-CSF level
using ELISA technique.
Results: G-CSF in BAL of IPF patients was significantly higher compared to
control group and it showed significant positive correlation with both neutrophil count
in BAL & the severity of the disease. Neutrophil count in BAL of patients was
significantly higher compared to control group.
Conclusions: G-CSF has a high level in BAL of IPF patients & it correlates
positively with severity of the disease.