2024-03-29T04:12:47+03:30
http://armaghanj.yums.ac.ir/browse.php?mag_id=57&slc_lang=en&sid=1
57-863
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Effect of Zinc Sulfate onPeptic Ulcer Disease
k
Yazdanpanah K *,
kyazdan4@yahoo.com
n
Moghimi
Ghaderi
v
Yousefinejad
Introduction & Objective: in vitro studies shown the effect of zinc sulfate on healing of ulcers but limited in vivo studies have been done to demonstrate this effect in human. This study was conducted to investigate the effect of zinc sulfate on peptic ulcer disease Materials & Methods: This is a double blind randomized clinical trial study. We studied people who referred to endoscopy clinic in Sanandaj Besat hospital during 2002-2003. The patients were divided into two groups, case group (n=45) and control group (n=58). Only patients who had duodenal and stomach ulcer were included. All patients received standard treatment for ulcer consisting of amoxicillin, metronidazole, omeprazole and bismuth. Interventional group received one zinc sulfate capsule (220 mg) every other day. After four weeks endoscopy was performed for each patient. Data analysis was done by SPSS software using descriptive statistics, x², Fisher exact and T test. Results: There was no difference between the case and control group in factors such as place of residency, smoking, alcohol and NSAID drug consumption and ulcer size. The mean size of ulcers in case group before and after treatment were 24.65±17.72 mm and 3.8±7.3 mm while in control group were 22.51±21.22 mm and 5.7±10.8 mm, respectively. The differences were not statistically significant. Conclusion: Zinc compound could be effective in healing peptic ulcer however, more studies with higher doses of zinc are required to determine its effective dose.
2007
4
01
1
9
http://armaghanj.yums.ac.ir/article-1-863-en.pdf
57-864
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
The Bupivacaine Effects on Opioids Usage and Admission Duration in Patients Underwent Inguinal Hernia Repair
HR
Khorshidi
khorshidi_h2007@yahoo.com
MH
Azimian
MM
Fazlian
ABSTRACT:
Introduction & Objective: Postoperative pain management and
narcotic usage after inguinal hernia repair is an important concern
for anesthesiologists and surgeons. The purpose of this study was
to find out whether the use of local anesthetic nerve block in
ilioinguinal and iliohypogastric region by bupivacaine could reduce
postoperative pain and hospital admission periods after inguinal
hernia repair.
Materials & Methods: In a randomized clinical trail, 100 patients
with diagnosis of unilateral inguinal hernia undergoing inguinal
hernia repair were randomly allocated to two groups. The patients
in the intervention group (n= 50) received bupivacaine for
ilioinguinal and iliohypogastric nerve blocking, while those in the
control group (n =50) received nothing. Then opioids (methadone)
usage and hospital admission duration were evaluated in the two
groups. The collected data were then analyzed by SPSS software
using descriptive and analytic methods (Chi square and student t
test).
Results: The mean admission times were 1±0.4 and 2±0.91 in the
intervention and control groups respectively and the difference was
statistically significant (p<0.01). Also the number of the patients
who intermittently received methadone was less in the intervention
group in comparison with that of the control (p<0.05). Furthermore,
intervention group received less amount of methadone during their
admission (p<0.05).
Conclusion: Local anesthetic nerve block in ilioinguinal and
iliohypogastric region by bupivacaine could reduce opioids usage
and the duration of hospital stay after inguinal hernia repair.
Inguinal hernia
Bupivacaine
Ilioinguinal nerve Block
2007
4
01
11
18
http://armaghanj.yums.ac.ir/article-1-864-en.pdf
57-865
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Evaluation of Antinociceptive Effect of Galbanum by Formalin Test in Mice
A
Zarifkar
M
Karami-Kheirabad
marya.karami@gmail.com
M
Edjtehadi
K
Rastgar
M
Ghalje
ABSTRACT:
Introduction & Objective: Ferula gummosa Boiss (Apiaceae) is a
perennial plant native to Iran and Afghanistan. Like many plants,
this species contains active biological compounds including
monoterpenes, alfa pinene and alkaloids which have been
demonstrated in phytochemical analysis of different extract of this
species. In Iranian traditional medicine Ferula gummosa has been
used in intestinal disorders, asthma and convulsion. Previous
studies showed that Galbanum is effective in relieving pain in hot
plate test model. In this study analgesic effect of intra peritoneal
injection of Galbanum (Ferula exudates) was evaluated by formalin
test and was compared with the analgesic effect of morphine and
non-steroidal anti-inflammatory drugs.
Material & Methods: This experimental study was done from July
2003 through 2004 in Shiraz University of Medical Sciences. 120
male Syrian mice weighing 25-32g, in ten groups were used in this
study. Mice were pretreated intra peritoneally (i.p.) 15 minutes
before formalin injection, with Galbanum (100 mg/kg), morphine
(4;6 mg/kg) and sodium salicylate (100;200 mg/kg). In vehicle
groups, equal volume of solvent (normal saline and/or DMSO) was
injected 15 minutes before formalin test. In diclofenac- sodium
(5;10 mg/kg, i.p.) and piroxicam (50 mg/kg, i.p.) groups, animals
were pretreated with these drugs 30 minutes before formalin
injection. Control group was not pretreated with any drug before
formalin test. Data obtained from formalin test were expressed as
Mean±SEM and were analyzed by ANOVA and Tukey test.
Results: Results of the present study showed that intra peritoneal
injection of Galbanum (100 mg/kg) reduced the pain score in acute
phase of formalin test (2.28±0.05) and also in chronic phase
(1.09±0.03). These differences were significant, in comparison with
control values, in both phases (p<0.05).
Conclusion: According to our findings, intra peritoneal injection of
galbanum (100 mg/kg), like NSAIDs and morphine, reduces acute
and chronic pain in formalin test. Moreover, Galbanum along with
diclofenac has additive effect at chronic phase of formalin test,
which means that it may have an anti-inflammatory effect as well.
2007
4
01
19
27
http://armaghanj.yums.ac.ir/article-1-865-en.pdf
57-866
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Prevalence of the cagA-Positive Helicobacter pylori Strains Isolated from Gastric Biopsy Specimens in Shahrekord
A
Doosti
doostiiranii@yahoo.com
GA
Rahimian
J
Nassiri
P
Yavari-Forushani
ABSTRACT:
Introduction & Objective: Helicobacter pylori are among
the important pathogens responsible for chronic gastritis,
peptic ulcer and gastric cancer. The present study aimed to
comparatively evaluate PCR and RUT methods for detection
of H. Pylori and determination of the prevalence of the cagApositive
Helicobacter pylori strains in Shahrekord.
Materials & Methods: This is a molecular epidemiology study
conducted in 1385 on biopsy samples collected from 120 patients
with dyspeptic symptoms who were referred to endoscopy
department of Hajar hospital of Shahrekord. In order to detect H.
pylori, RUT method was used at first and then DNA was directly
extracted from biopsy specimens. PCR-amplification was
preformed for the ureC and then for cagA gene.
Results: The H. pylori infection was found in 74 (61.66%) of the
patient by RUT method. In parallel, ureC PCR detected H. pylori in
103 (85.83%) of patients. All RUT-positive patients were found to
be ureC-PCR positive, too. The cagA-positive H. pylori strains
were found in 83.5 percent of isolated strains.
Conclusion: These findings indicate that ureC PCR is more
sensitive than RUT for diagnosis of H. pylori infection. In addition,
the high prevalence of the CagA-positive H. pylori strains is
present in Shahrekord.
Helicobacter pylori
Polymerase Chain Reaction(PCR)
Cytotoxin associated gene A(cagA)
2007
4
01
29
38
http://armaghanj.yums.ac.ir/article-1-866-en.pdf
57-867
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Change of Astrocytes Number in CA2 Subfield of Hippocampus after Spatial Learning
M
Jahanshahi
Y
Sadeghi
SA
Hosseini
N
Naghdi
ABSTRACT:
Introduction & Objective: The hippocampal formation is a part of
limbic system that plays an important role in memory and learning.
The hippocampus is divided into three subfields: CA1, CA2 and
CA3. In addition to pyramidal neurons and interneurons, the
astrocytes play important roles in hippocampus, probably in
memory and learning. In fact, learning needs some instruments for
information storage and information maintenance mechanisms like
memory. On the other hand, memory is always accompanied with
learning. This study was conducted to evaluate the changes in
number of astrocytes in CA2 subfield of hippocampus in rats due to
spatial learning.
Materials & Methods: In this experimental study, with the use of
Morris Water Maze and two other techniques (Reference and
Working memory methods) in the behavioral laboratory of
physiology department of Pasteur institute, 15 male Wistar rats
were used. Five rats were included in control group and 10 rats in
the other two groups (each 5 rat). After performing the educational
experiments, animal brain was removed and after histological
processing, the slides were stained with PTAH to show the
astrocytes. The obtained data were analyzed by SPSS, using T
test and variance analysis.
Results: The results showed a significant difference in astrocytes
number of CA2 area between control and reference memory
group. Also the difference between control and working memory
groups was significant. Comparing the two educated groups, a
significant difference was found in the number of astrocytes in
those groups.
Conclusion: The number of astrocytes in CA2 area of
hippocampus of rats increased due to spatial learning.
Hippocampus
CA2
Astrocytes
Spatial Learning
PTAH staining
2007
4
01
39
48
http://armaghanj.yums.ac.ir/article-1-867-en.pdf
57-868
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
The Influence of Iontophoresis on Tretinoin Release from Topical Preparations and Its Penetration across Rat Skin
M
Heshmatipour
N
Tavakoli
tavakoli@pharm.mui.ac.ir
R
Ebrahimi
ABSTRACT:
Introduction & Objective: Acne vulgaris is one of the most
prevalent skin diseases which is common in adolescent of both
sexes. Tretinoin has been used therapeutically for its comedolitic
effects and inhibition of comedone rupture in acne. It is available
in 0.01% to 0.1% as cream, gel or lotion. There have been a few
clinical reports of the positive effects of iontophoresis with
tretinoin on acne scars. The aim of this study was to investigate
the effect of iontophoresis field on transport of tretinoin across
synthetic membrane and excised rat skin.
Materials & Methods: Topical formulations of tretinoin marketed
in Iran ( Retin-A cream, Retin-A gel, Tretinoin cream 0.025% and
Tretinoin gel 0.025%) were assessed in terms of drug assay and
content uniformity. The in vitro release and penetration
characteristics of tretinoin from dermatological preparation was
studied through a hydrophilic Dora pore diffusion barriers and
membrane excised rat skin using Franz diffusion cell over a
period of 2h. These two tests were also accomplished either with
or without the presence of an iontophoresis field. The current
density of iontophoresis applied field was constant, 0.5 mA/cm2.
The amount of drug released from preparations was determined
spectrophotometrically at max =352nm.
Results: The in vitro release of tretinoin through synthetic barrier
with an iontophoresis field showed that the cumulative percent of
released drug at the end of each experiment was 17.5%, 26.5%,
19% and 54% for Tretinoin gel, Retin-A gel, Tretinoin cream and
Retin-A cream, respectively. This was significantly higher than
the observed one for release of tretinoin without application of a
DC electric field. In addition, the results showed a significantly
higher iontophoretic transport of tretinoin compared to passive
flux for excised rat skin.
Conclusion: The application of an electric current for a limited
period of time produced higher post-iontophoresis fluxes of
tretinoin than passive diffusion. With application of iontophoresis
field, the in vitro release and transport of drug for different
formulations of tretinoin follow the zero order kinetics.
Iontophoresis
Rat skin
Tretinoin
2007
4
01
49
59
http://armaghanj.yums.ac.ir/article-1-868-en.pdf
57-869
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Comparison of Survey Used of Polyester Resin and Glycerin Instead of Silicon in S10 Technique of Plastination
HR
Ghafari
E
Esfandiari
M
Jafari Barmak
GH
Dashti
A
Shahraki
ABSTRACT:
Introduction & Objective: Teaching human anatomy, at any level,
relies not only on the expertise of a tutor but also on the availability
and use of good teaching aids. Plastination specimens have a
unique position as a teaching aid to exhibit accurate anatomical
structures and are easy to be stored and handled by students. The
aim of this study was to assess the comparative use of polyester
resin instead of silicon in S10 technique of plastination.
Materials & Methods: This is an applied experimental study which
was performed on a human body after fixation of the cadaver .The
polymer was prepared by mixing glycerin and polyester resin and
the cobalt (accelerator) and peroxide (hardening material) were
added to it. Dissection, dehydration, defatization and impregnation
of the body were carried out. Finally, the palatinate of specimen was
compared with the palatinate of Heidelberg university (standard
group). The collected data were analyzed by SPSS software using
paired T-test.
Results: The prepared palatinate specimen was dry, nontoxic and
without noxious fumes and showed a normal anatomical position of
structure. Flexibility, elasticity and traction were compared with
those of standard specimen and no significant differences were
observed. Injected colored polymers in vessels were detected
easily.
Conclusion: According to this study, the palatinate specimen
prepared by polyester resin polymer provided an excellent
opportunity to demonstrate and study the dissected areas of the
difficult structures which can be of great benefit in teaching gross
anatomy. In addition, because of the durability, safety, reduction in
toxic and noxious fumes of formalin, the palatinate specimens can
be unique materials as a teaching aid along with the Wet
specimens.
Plastination
Polyester resin
Silicon
Flexibility
Force
Tension
2007
4
01
61
68
http://armaghanj.yums.ac.ir/article-1-869-en.pdf
57-870
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Effects of Dietary Calcium on Serum Lipids, Glucose and Insuline in Male Rats
JM
Malekzadeh
SA
Keshavarz
s_akeshavarz@yahoo.com
F
Siassi
M
Kadkhodaei
MR
Eshraghian
AR
Dorosti Motlagh
A
Aliehpoor
M
Chamari
ABSTRACT:
Introduction & Objective: There are different methods for
improving hypercholesterolemia, insulin resistance and
hypertriglyceridemia, the major risk factors of cardio-vascular
disease. Calcium, a nutrient essential for many vital functions of
the body is now receiving much attention for its possible
hypolipidemic effects. The large bodies of studies on the effects of
calcium on the serum lipids have shown conflicting results and also
there is little evidence for its effects on serum insulin and glucose.
Materials & Methods: In this study, the researchers evaluated the
effects of three levels of dietary calcium (0.2, 0.5 and 1.2 gram%
diet) on serum cholesterol, HDL-cholesterol, LDL-Cholesterol and
serum insulin and glucose in male Sprague-Dawley rats. The
amount of fecal fat excretion was measured to determine the
possible mechanism of lipid lowering effects of calcium.
Results: Findings showed that increasing dietary calcium lowerd
the serum cholesterol (p=0.04), LDL-cholesterol (p=0.02) but had
no significant effects on HDL-cholesterol, serum insulin and
glucose. There was a dose dependent increase in fecal fat
excretion but was not statistically different on a percent basis.
Conclusion: It can be concluded that calcium is an effective
hypocholesterolemic nutrient but its effects on serum triglycerids,
glucose and insulin need to be evaluated.
2007
4
01
69
78
http://armaghanj.yums.ac.ir/article-1-870-en.pdf
57-871
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
The Predictive Value of Computed Tomography in Jugular Vein by Head and Neck Tumors
L
Aghaghazvini
H
Sharifian
H
Mazaher
M
Aghaghazvini
P
Dabirmoghaddam
SH
Aghaghazvini
M
Assadi
assadipoya@yahoo.com
ABSTRACT:
Introduction & Objective: Awareness of invasion of the walls of
the cervical vessels by tumor is of great clinical importance before
surgery. This study was designed to assess the diagnostic worth of
Computed Tomography (CT) in distinguishing jugular vein (JV)
invasion by oral –maxillofascial and neck malignant tumors.
Material & Methods: CT with contrast was performed on 46
patients who had oral –maxillofascial and neck malignant tumors
before surgical intervention. The CT appearance of all tumors was
prospectively compared with surgical findings.
Results: The abnormal CT manifestation of the patients with JV
involvement consisted of 5 types: type I, tumor encasement of
greater than 270 degrees of circumference of the jugular vein in 8
tumors type II, tumor encasement of greater than 180 degrees of
circumference of the jugular vein in 13 tumors type III,
compression of JV in 10 and displacement of JV in 3 tumors type
IV, the segmental deletion of fat planes between tumor and JV in
20 tumors type V, obliteration of JV on segmental axial CT views
in 7 tumors. The sensitivity, specificity and positive predicative
value were 34.4%, 86.7% and 80% for type I, 59.1%, 66.7% and
72.2% for type II, 57%, 62.5% and 54.4% for type III, 91%, 45.8%
and 60.5% for type IV and 38%, 88% and 70% for type V. In
addition, correlation coefficient of JV for types I and IV was
statistically significant.
Conclusion: Although a variety of CT findings was helpful in
assessing the JV but types I and IV had more accuracy. Our study
demonstrated that although CT images were not an accurate and
definite way of jugular vein assessment in head and neck tumors,
they could be a useful approach in primary staging, tumoral
extension and therapeutic management.
Jugular vein
Computed Tomographyو Head and Neck Tumors
2007
4
01
79
88
http://armaghanj.yums.ac.ir/article-1-871-en.pdf
57-872
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Z
Hashemizadeh
M
Motamedifar
motamedm@sums.ac.ir
M
Ziyaeyan
2007
4
01
89
97
http://armaghanj.yums.ac.ir/article-1-872-en.pdf
57-873
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Assess the Patency and Complications of AV Fistulas in Patients with Chronic Hemodialysis
S
Mehrabi
Mehrabis@Sina. Tums.ac.ir
SR
Mirsharifi
A
Jafarian
ABSTRACT:
Introduction & Objective: In patients with chronic renal failure
who need chronic hemodialysis, AV fistula is one of the most
proper ways of vascular access. The aim of this study was to
assess the patency and complications of AV fistulas in patients
with chronic hemodialysis.
Materials & Methods: In this descriptive study 82 patients with
chronic renal failure, who underwent AV fistulas in a 5 year- period
of time in Imam Khomeini Hospital Center were enrolled. Age,
gender, fistulas patency, complication rate and their relation with
diabetes, hypertension and history of Shaldone were assessed.
The collected data were analyzed by T and Chi-square test using
SPSS soft ware.
Results: the age mean of patients was 46.9±18.8 years. 46
patients (%56.1) were male. The mean of age was significantly
higher in patients with complication compared to patients without
complication. History of shaldone and hypertension were
significantly higher in patients with bad fistula blood flow compared
to patients with good fistula blood flow. History of shaldone,
diabetes and hypertension were significantly higher in patients with
complication compared to patients without complication. Female
patients were significantly prone to aneurysm than males. History
of transplants rejection was significantly higher in patients with
aneurysm than in those without aneurysm. History of hypertension
was significantly higher in patients with aneurysm and thrombosis
compared to those without aneurysm and thrombosis. History of
shaldone and Diabetes was significantly higher in patients with
thrombosis compared to those without thrombosis.
Conclusion: History of shaldone, Diabetes and Hypertension were
significantly higher in patients with complication and bad fistula
blood flow.
KEYWORDS:AV fistulas
Chronic hemodialysis
Patency
Complications
2007
4
01
99
106
http://armaghanj.yums.ac.ir/article-1-873-en.pdf
57-874
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Effect of Instillation of Morphine and Dexamethasone in Epidural Space on Postoperative Pain in Discectomy Operation
K
Tavakol
kamtavakol@yahoo.com
AH
Daneshi
K
Karimzadeh Shirazi
ABSTRACT:
Introduction & Objective: Discectomy for nucleous pulposus herniation is
one of he most surgeries in spinal column. In this surgical treatment,
postoperative pain is a problem which results in more hospital stay and
less daily activity. Postoperative pain control is difficult because opoids
don't relieve moderate and severe pain alone. It is believed that
corticosteroid and local anesthetic agents or narcotics improve sciatic pain.
In this study we compare the effect of different doses of morphine and
dexamethasone by placebo on post discectomy operative pain.
Materials & Methods: This is a randomized double blind clinical trial in
which 90 selected patients, ASA 1-2, with acute-onset herniated nucleus
pulposus that were refractory to conservative treatment were enrolled.
Subjects were randomly divided into 6 groups and underwent discectomy
under equal general anesthesia. Before the closure operational incision,
the first group received 5 cc lidocaine %2, second group 5cc normal saline
third group 0.5 mg morphine and 8 mg dexamethasone, forth group 1mg
morphine and 8 mg dexamethasone, fifth group 1.5 mg morphine and 8 mg
dexamethasone, and the last group 2 mg morphine for every level of
discectomy and 8mg dexamethasone . Drugs were flushed on dura matter
and operation field. Volume of all drugs was increased to 6 cc by adding
sterile distilled water. Postoperative back and radicular pain was scaled 6,
12, 18 and 24 hour after operation using visual analogue scale (VAS) and
recoded analgesic requirement. Collected data was analyzed by SPSS
software using Mann Whitney U and Kruskal-Wallis tests.
Results: patients of group 1 to 3 did not showed significant changes in
postoperative pain and consumption of analgesic, but when dose of
morphine increased, these changes became significant especially in dose
of 2 mg for every level of discectomy.
Conclusion: It seems that Instillation of morphine and dexamethasone in
epidural space after discectomy decreases patient’s postoperative pain
which result in reduction in narcotic use.
www
KEYWORDS:Discectomy
Epidural
Morphine
Dexamethasone
Postoperative Pain
2007
4
01
107
115
http://armaghanj.yums.ac.ir/article-1-874-en.pdf
57-876
2024-03-29
10.1002
Armaghane Danesh
armaghanj
1728-6506
1728-6514
10.61186/armaghanj
2007
12
1
Fever of Unknown Origin, a Prospective Multicenter Study of Patients with FUO in Hospitals of Shahid Beheshti University of Medical Sciences in 2003
O
Eilami
MR
Salari Shahrebabaki
SD
Shoaei
L
Gachkar
ABSTRACT:
Introduction & Objective: Fever of Unknown Origin (FUO) has
different etiologies due to new diagnostic procedures and
geographic areas. This study aimed to evaluate the patients with
FUO in hospitals of Shahid Beheshti Universty of Medical
Sciences.
Materials & Methods: In this survey case series admitted patients
with impression of FUO in infectious diseases wards of Shahid
Beheshti University of Medical Sciences of Iran in 2003 were
studied. 52 patients had fever over 38.3 ºC for 3 weeks and their
disease was not diagnosed after 3 visits or 3 days of admission.
Results: 54% of the patients were male and 46% were female.
85% of the cases were under the age of 60 years. The most
common etiology of FUO was Infectious diseases (36.5%), and
neoplasm (21%), miscellaneous (17.5%), undiagnosed (13.5%),
and connective tissue diseases (11.5%) respectively.Tuberculosis
(7.7%), Intra-abdominal abscess (7.7%), lymphoma (11.5%), drug
fever (5.8%) and autoimmune hepatitis (3.8%) were the most
common infectious diseases.
Conclusion: Results of this study are comparable with those in
other developing countries and infectious disease is the most
common causative agent of FUO.
Fever of Unknown Origin (FUO)
Tuberclosis
Intra-abdominal Abscess
Neoplasm
Lymphoma
Drug fever
Connective tissue diseases
Autoimmune hepatitis
2007
4
01
117
124
http://armaghanj.yums.ac.ir/article-1-876-en.pdf