Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
osteochondral lesions involve the articular cartilage and underlying subchondral bone , and most often affect the knee and the talus ( 1 ) .
osteochondral lesions of the femoral head are uncommon , and few studies have reported the imaging findings of such lesions . since this condition occurs in relatively young patients , and osteochondral damage puts joints at high risk of subsequent degeneration ( 2 ) , timely recognition of this disorder is important for proper treatment . herein , we review previous literature related to osteochondral lesions of the femoral head and 796report a case in which lesion involving the bilateral femoral heads was observed .
this lesion manifested as subchondral cysts according to the initial radiography images , and led to further evaluation by computed tomography ( ct ) arthrography and immediately obtained magnetic resonance imaging ( mri ) scan that revealed overlying articular cartilage defects .
a 20-year - old female patient was referred to our hospital from a local hospital .
her chief complaint was pain in both hips along with severe right side pain of approximately 2 months duration .
notably , however , she had been a taekwondo athlete in high school for several years . on clinical examination ,
plain radiography of the hip showed well - defined subchondral radiolucent lesions with a subtle sclerotic rim in the superior portion of the right femoral head ( fig .
the acetabuli in both sides of the hip displayed mild dysplasia with lower limit of normal ( center - edge angle , 24 - 25 degrees ) .
no signs of degeneration , such as joint space narrowing or juxta - articular sclerosis , were observed , except for subtle osteophyte around the head - neck junction of the right femur .
deformations of the femoral head , such as flattening , or the presence of crescent signs were also absent .
based on imaging findings , a provisional diagnosis of avascular necrosis with subchondral cysts could not be excluded . to further investigate the lesion ,
1b , c ) revealed several subchondral cysts that were hypointense on the t1-weighted images ( repetition time [ tr]/echo time [ te ] , 374/20 ) and hyperintense on the t2-weighted fat - suppressed images ( tr / te , 1500/29 ) .
the overlying portion in this region revealed a focal articular cartilage defect measuring about 10  15 mm in size , consistent with an osteochondral lesion .
no surrounding bone marrow edema was observed , and no cartilage damage was noted on the opposite site of the acetabulum .
the scintigraphy scan with 99 m technecium methylene diphosphonate showed no increased activity in the femoral head .
on arthroscopy , chondral damage was noted in the superior portion of the femoral head .
follow - up plain radiography of the hip performed about a year later revealed subchondral cysts in the superior portion of the left femoral head ( fig .
the patient reported no incidence of trauma in the meantime , other than mild hip discomfort .
1f ) scans of the left hip also showed several subchondral cysts , measuring about 14  13 mm in size , with associated overlying articular cartilage loss .
retrograde inspection of previous hip mri scans performed at the local referral hospital 2 months before the first visit to our hospital revealed lesions of the left femoral head with abnormal signal intensity , including hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images ( fig .
this led us to hypothesize that the subchondral cyst lesion had progressed from a pre - existing lesion already present one year before .
the chondral defect was confirmed by arthroscopy and core decompression with a bone graft was performed , as had been done for the right side .
osteochondral lesions involve articular cartilage and the underlying subchondral bone , and mainly affect the knee and the talus ( 1 ) .
osteochondral lesions of the femoral head are rare and the prevalence is unclear ( 3 ) .
detailed reports of the imaging findings of such lesions are also quite limited . therefore , osteochondral lesions of the femoral head can be easily overlooked , unless radiologists are suspicious of osteochondral lesions that develop in the femoral region .
furthermore , osteochondral lesions of the femoral head are known to cause joint degeneration ( 2 ) .
we diagnosed the osteochondral lesion by identifying the accompanying overlying articular cartilage defects by ct arthrography and mri , which were performed for further evaluation .
we excluded a diagnosis of avascular necrosis due to the absence of a double line sign or a crescent sign of the femoral head on mri .
moreover , no signs indicative of primary osteoarthritis , such as joint space narrowing or juxta - articular sclerosis in both the acetabulum and femoral head , were observed .
the causes of osteochondral lesions have not yet been elucidated , and are likely to be multifactorial ( 4 ) .
one of the well - known causes of the osteochondral lesion of the femoral head is legg - calv - perthes disease . in this secondary lesion
, however , separated subchondral bone with articular cartilage from the joint surface is the main feature , which is different than our case .
other etiologies of osteochondral lesions in the hip include previous infection , genetics , ischemia or trauma ( 5 , 6 ) .
many studies have reported damages incurred by repetitive traumas ( 7 , 8 , 9 ) .
( 10 ) reported normal plain radiographic finding but mri detection of a subchondral lesion in an athlete with continuous hip pain , and suggested that although an athlete may not recall a specific incidence of past trauma , shearing injury of the cartilage by subluxation during joint rotation or impact damage caused by forces exerted by jumping could have occurred .
( 7 ) demonstrated that osteochondritis dissecans of the elbow can result from articular cartilage damage inflicted by repeated trauma .
nakamura et al . ( 6 ) reported an osteochondral lesion of the femoral head believed to have originated from repeated impact and high axial loads in a fencer .
our patient was previously an athlete , and so could have developed the osteochondral lesions by repetitive trauma , despite the lack of recollection of any particular past trauma .
( 10 ) also reported abnormal bone marrow signals from an osteochondral lesion on the femoral head .
this lesion exhibited hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images , along with cartilage surface irregularities of the medial portion . in our case , although the cartilage surface irregularities were not immediately apparent from the previous mri scans taken at the local referral hospital , lesions displaying hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images were present in the left femoral head .
an articular cartilage defect lesion accompanied by subchondral cysts was found about a year later , similar to the lesion previously observed on the right femoral head .
we concluded that an osteochondral lesion was already present at the time of the previous mri scan , and that this lesion progressed to the lesion with subchondral cysts .
it may often be necessary to distinguish osteochondral lesions from avascular necrosis in differential diagnoses .
the articular cartilage of the femoral head has been shown to be unaffected in the majority of cases of avascular necrosis , whereas this cartilage is often damaged in osteochondral lesions . moreover ,
avascular necrosis of the femoral head manifests itself as a somewhat broader lesion , often accompanied by serpiginous , low signal lines or crescent signs ( 11 ) . on the other hand ,
osteochondral lesions often reveal smaller - sized areas with wedge - shaped signal abnormalities , or a narrow inlet with deep nest - shaped lesions , as seen in this case ( 12 , 13 ) .
patient age , in particular being younger , is also helpful in distinguishing this condition from avascular necrosis ( 10 ) .
10 ) are thought to be indicative of lesions in the acute or subacute stage . in the chronic stage , however , a progressed degenerative bony lesion in the form of subchondral cysts , as seen in our case , or perhaps even a sclerotic change exhibiting hypointensity on the t1- and t2-weighted images , may be observed ( 6 ) . although some authors have reported that high uptake on the scintigraphy represents inflammation or lesion healing , no increased uptake was observed in our case , probably because the lesions are in the chronic stage .
in addition , young patients , especially those with a previous trauma or a history of being an athlete , are potential candidates for osteochondral lesions .
radiologists should look for bony lesions associated with articular cartilage defects in the femoral head , which could be indicative of an osteochondral lesion , similar to the lesions that are known to occur in the knee or the talus .

Answer:
osteochondral lesions of the femoral head are uncommon and few studies have reported their imaging findings .
 since joints are at risk of early degeneration after osteochondral damage , timely recognition is important .
 osteochondral lesions of femoral head may often be necessary to differentiate from avascular necrosis . here , we report a case of osteochondral lesions on bilateral femoral heads .
 this lesion manifested as subchondral cysts in initial radiographs , which led to further evaluation by computed tomography arthrography and magnetic resonance imaging , which revealed overlying cartilage defects .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
unless otherwise stated , all chemicals and solvents were purchased from commercial suppliers in reagent- or technical - grade quality and used directly as received without further purification .
the bis(arylimino)acenaphthene ligands were prepared from acenaphthenequinone and the corresponding substituted anilines in anology to literature methods.[14 , 27 ] the rhenium complex 1 was synthesized as previously reported .
general procedure for the preparation of 2 and 3 : equimolar amounts of re(co)5cl ( 0.05 g , 0.14 mmol ) and the corresponding bis(arylimino)acenaphtene ligand were refluxed in dry toluene ( 4 ml ) for 30 min .
complete precipitation of the product was obtained upon cooling the reaction mixture to room temperature and slow addition of n - hexane .
as a service to our authors and readers , this journal provides supporting information supplied by the authors .
such materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors

Answer:
rhenium(i ) carbonyl complexes carrying substituted bis(arylimino)acenaphthene ligands ( bian - r ) have been tested as potential catalysts for the two - electron reduction of carbon dioxide .
 cyclic voltammetric studies as well as controlled potential electrolysis experiments were performed using co2-saturated solutions of the complexes in acetonitrile and acetonitrile  water mixtures .
 faradaic efficiencies of more than 30 % have been determined for the electrocatalytic production of co. the effects of ligand substitution patterns and water content of the reaction medium on the catalytic performance of the new catalysts are discussed .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the ultrasound ( us ) appearance of testicular microlithiasis ( tm ) was first described by doherty et al .   in 1987 .
the prevalence of tm in symptomatic korean men was found to be 6.0% with significant co - occurrence of tm , testicular cancer , and infertility by yee et al .
although the cause - and - effect relationships are unclear , tm has been seen in patients with cryptorchidism , varicoceles , infertility , testicular torsion , klinefelter syndrome , pulmonary alveolar microlithiasis , neurofibromatosis , acquired immunodeficiency syndrome , intratubular germ cell neoplasia , and most importantly , primary testicular neoplasms .
reported that 74% of testes with tumors had associated ipsilateral tm on radiological inspection ; whereas , only 8% of testicular specimens with benign conditions had microcalcifications .
although chen et al .   reported that there was a significant difference in the rate of malignancy in males with tm compared with those without tm , the question remains whether tm independently increases the risk of testicular malignancy in taiwanese men .
, after reporting an association between tm and testicular tumor specimens , suggested in 1982 that radiographic studies be incorporated into diagnosing tm because of the perceived risk for testicular cancer in testicles with microlithiasis
performed us follow - up in 9 of 22 patients with tm for a mean of 32 months without any newly developing tumors being diagnosed .
reported similar results ; therefore , a regular scrotal us is controversial in asymptomatic tm patients .
the current recommendations , including those of the european association of urology , are that the presence of microlithiasis alone is not an indication for a regular scrotal us in the absence of other risk factors ( size<12 ml or atrophy , inhomogeneous parenchyma ) .
however , there have been no reports describing the changes in calcification over time in pediatric patients with tm .
the study protocol was approved by the institutional review board of the asan medical center .
the medical records from july 1997 to august 2014 of the asan medical center , a tertiary referral center , were retrospectively screened for patients diagnosed with tm by scrotal us .
twenty - three tm patients were included who had undergone scrotal us at least twice .
we analyzed the patient characteristics , clinical manifestations , specific pathological features , and clinical outcomes .
we measured the calcified area in maximum cross - sectional area , and we compared the calcific density in the initial diagnostic us and the final follow - up us .
we defined the testis and the calcified area in terms of their maximal cross - sectional area and calculated those areas using image j software ( national institutes of health , bethesda , md , usa ) ( fig .
patients that showed microlithiasis in three or more sections were defined as diffuse type , and patients with microlithiasis in less than three sections were defined as focal type ( fig .
we classified the patients into three groups according to the change of microlithiasis : an increased group , 20% increase in microlithiasis ; a decreased group , 20% decrease in microlithiasis ; and a no change group , < 20% increase or decrease .
differences were analyzed by a paired t - test , and crosstabs were used to assess dependent samples . in this study p - values < 0.05 were considered statistically significant .
the mean age at presentation was 11.34.6 years , and the follow - up period ( interval of fist us and last us ) was 79.138.8 months ( range , 25.4 - 152.9 months ) .
the mean age at last follow - up was 17.85.8 years ( range , 6.4 - 26.9 months ) .
follow - up occurred for 19 of 23 patients over puberty ( defined as > 13 years old ) .
of the 23 patients 20 had bilateral tm , 2 patients had unilateral tm , and 1 patient had an atrophic testis .
less frequent comorbid conditions included testicular torsion ( 3 patients , 13.0% ) , epididymitis ( 3 patients , 13.0% ) , varicocele ( 2 patients , 8.7% ) , hydrocele ( 2 patients , 8.7% ) , and epididymal cyst ( 2 patients , 8.7% ) .
calcific density was increased at the last follow - up us compared with the initial us ; however , this finding was not statistically different ( 3.74%6.0% vs. 3.06%4.38% , respectively , p=0.147 ) .
we divided the subjects into two groups ( focal vs. diffuse ) based on the distribution of tm .
we classified 23 testes as having focal tm and 20 testes as having diffuse tm .
in focal tm calcific density decreased but not significantly ( 0.72%0.55% vs. 0.66%1.03% , p=0.813 ) . on the other hand ,
the calcific density of diffuse tm show a trend toward increase ( 5.8%5.2% vs. 7.3%7.4% , p=0.457 ) ( table 2 ) ( fig .
3 ) . to clarify the tendency of tm calcification toward increase vs. decrease we divided the subjects into three groups based on the calcific density change of tm ( increase : increased > 20% ; decrease : decreased > 20% ; no change : < 20% increase or decrease ) .
we categorized 14 testes as increased , 18 testes as decreased , and 11 testes as no change .
half of the patients with diffuse tm were assigned to the increased group , a proportion significantly higher than focal tm ( 10/20 [ 50% ] in diffuse tm , 4/23 [ 17.4% ] in focal tm , p=0.049 ) ( table 3 ) .
in addition , 5 of 8 testes with cryptorchidism ( including 2 with bilateral cryptorchidism ) were categorized into the increased group .
previous tm studies have focused only on the relationship between tm and testicular cancer , and not on the natural course of this disease progression . in our current study , we report the natural course of calcific density changes in pediatric tm during pubertal development .
the mean age at presentation was 11.3 years and the mean follow - up period of approximately 5 years allowed follow - up of 23 patients over pubertal development . despite a follow - up interval that allowed potential pubertal changes to the testis , none of our patients developed testicular cancer or new abnormal symptoms . by contrast , there are some reported cases of patients with a known tm on us exam that eventually developed a primary testicular cancer .
reported a yolk sac tumor developing in a 17-year - old boy being followed for bilateral tm that was originally detected because of an initial sonographic evaluation of unequal sized testes .
reported the case of a man with tm seen on a sonograph performed due to bilateral testicular pain who presented three years later with a metastatic germ cell tumor of the left testicle .
although , an association between tm and subsequent testicular tumors appears likely , whether there is a true cause - and - effect relationship remains unknown .
( 7 patients , 45 months)-used us to follow patients with tm and , similarly to our present results , did not detect the appearance of new testicular tumors .
compared with these prior studies , our current study incorporates more patients and a longer - term follow - up extending through puberty .
an additional strength of our study over previous studies is in our investigation of changes in calcified density of the tm .
one earlier study has reported nonquantitative changes in the prominence of tm on yearly us follow - up .
the tm was less prominent in one patient , unchanged in four , and two patients were lost to follow - up . to our knowledge , our present study is the first report to provide a quantitative analysis of calcific density in tm .
calcific density on us showed a nonstatistically significant trend toward increase over time in our study subjects .
reported a relationship between the number of microliths and testicular cancer after subgrouping subjects into four ranges based on the number of microliths . in our present study , we divided tm into two nearly equal groups based on the distribution pattern of calcification ( focal type [ 23 testes ] vs. diffuse type [ 20 testes ] ) that appear to differ in terms of calcification trends .
calcific density shows a trend toward a decrease in focal tm but toward an increase in 50% of the testes with diffuse tm .
notably , the majority of testes ( 5/8 ) in our study series with cryptorchidism , including those with bilateral cryptorchidism , were categorized as being in the increased calcification group .
during the follow - up through puberty of the microlithiasis in the 23 boys in our present study , we observed no significant changes in the density of their microliths and no development of testicular cancer ; however , we found that diffuse tm and cryptorchidism tend to increase calcific density .
hence , close observation is recommended in cases of tm combined with cryptorchidism and diffuse microlithiasis .

Answer:
purposetesticular microlithiasis ( tm ) is a relatively rare clinical entity of controversial significance characterized by the existence of hydroxyapatite microliths located in the seminiferous tubules .
 the aim of this study was to observe the natural course of changes in the calcific density of pediatric tm.materials and methodswe included a total of 23 tm patients undergoing scrotal ultrasound ( us ) on at least two occasions from july 1997 to august 2014 .
 we retrospectively analyzed the patient characteristics , clinical manifestations , specific pathological features , and clinical outcomes .
 we measured the calcified area and compared the calcific density between the initial and final uss.resultsthe mean age at diagnosis was 11.34.6 years , and the follow - up period was 79.138.8 months ( range , 25.4 - 152.9 months ) . during the follow - up period ,
 no patients developed testicular cancer .
 calcific density on us was increased in the last versus the initial us , but not to a statistically significant degree ( 3.74%6.0% vs. 3.06%4.38% , respectively , p=0.147 ) .
 when we defined groups with increased and decreased calcification , we found that diffuse tm was categorized into the increased group to a greater degree than focal tm ( 10/20 vs. 4/23 , respectively , p=0.049 ) .
 in addition , five of eight cases of cryptorchidism ( including two cases of bilateral cryptorchidism ) were categorized in the increased calcification group.conclusionsdiffuse tm and cryptorchidism tend to increase calcific density .
 close observation is therefore recommended for cases of tm combined with cryptorchidism and cases of diffuse tm .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
chronic cough is a frequent presenting complaint to not only the general practitioner but also the otolaryngologist and respiratory specialist .
diagnosis can be difficult , especially in primary care , but empirical treatment for common causes such as asthma , chronic obstructive pulmonary disease , gastro - oesophageal reflux disease , postnasal drip or drug - induced cough ( most commonly secondary to angiotensin converting enzyme inhibition ) is recommended when there are no associated worrying symptoms , and is successful in the majority of cases .
symptoms that may signify a rarer but more serious cause for chronic cough include the copious production of sputum , fever , sweats , unintentional weight loss , haemoptysis , clubbing , hoarseness and marked dyspnoea . here
we highlight a unique cause of chronic cough : the initial symptom of lymphoma compressing the brainstem .
a 69year - old gentleman presented to his general practitioner with a 3-month history of progressive unsteadiness . on further questioning
he also volunteered that these symptoms had been preceded by a chronic cough , which had no obvious precipitant , and which had failed to resolve . on examination he had truncal ataxia , to the point where he had difficultly remaining upright when walking , and exhibited gaze - evoked first - degree nystagmus in his left eye on looking to the right .
the patient had suffered an episode of labyrinthitis 10 years earlier , and so he was prescribed pharmacological therapy aimed at a presumptive diagnosis of a second episode .
successive trials of prochlorperazine , betahistine , cyclizine and arlevert were not noted to have any positive effect on the patient 's dizziness and he was referred for outpatient neurological opinion . by the time of specialist review , the patient 's symptoms had worsened and he now described periods of severe nausea , with progression of his ataxia to the point where he was unable to stand unaided .
he had also developed an area of hypoesthesia on the left side of his face .
eye movements were adjudged to be markedly abnormal with dysmetric horizontal saccadic movements in addition to his ongoing nystagmus . his right vestibular ocular reflex was reduced and his left upper limb movements lacked coordination .
gadolinium - enhanced magnetic resonance imaging ( mri ) of the brain revealed a homogenously enhancing , sharply demarcated 13 mm diameter lesion in the left posterior and lateral midbrain extending into the inferior cerebellar peduncle , with some adjacent oedema , suggestive of primary lymphoma ( see fig .  1 ) .
stereotactic brain biopsy confirmed diffuse large b - cell lymphoma ( dlbcl ) and subsequent bone marrow biopsy and computer tomography ( ct ) imaging showed no evidence of lymphoma at any additional anatomical site .

figure  1:gadolinium - enhanced t1-weighted mri images ( panes lettered with coronal ( a ) , axial ( b ) and sagittal ( c ) sections ) showing a homogenous enhancement of a clearly demarcated lesion in the left posterior and lateral midbrain with extension into the inferior cerebellar peduncle . gadolinium - enhanced t1-weighted mri images ( panes lettered with coronal ( a ) , axial ( b ) and sagittal ( c ) sections ) showing a homogenous enhancement of a clearly demarcated lesion in the left posterior and lateral midbrain with extension into the inferior cerebellar peduncle .
the patient embarked on idaram ( idarubicin , cytarabine , methotrexate , dexamethasone ) chemotherapy followed by two rounds of high - dose methotrexate mono - therapy .
imaging following treatment showed radiological remission and this is also seen on recent scans , now 2 years later ( see fig .  2 ) .
while the symptoms of cerebellar dysfunction have largely abated since discharge , the patient has , however , been continually troubled by his cough .

figure  2:compares initial t1-weighted gadolinium - enhanced mri images ( seen in panes on left hand side : a , c and e ) with those taken following completion of treatment ( panes on right : b , d and f ) . radiological remission is shown in the post - treatment images .
compares initial t1-weighted gadolinium - enhanced mri images ( seen in panes on left hand side : a , c and e ) with those taken following completion of treatment ( panes on right : b , d and f ) . radiological remission is shown in the post - treatment images .
otolaryngology assessment , including symptom review , medication history , endoscopic evaluation and chest x - ray , was unable to elucidate any cause for cough other than the presumed effects of the medullary lesion .
empirical trials of nasal steroids , nasal saline washes , high - dose proton pump inhibitor and inhaled bronchodilators were all unsuccessful .
coughing is a protective motor reflex under both voluntary and involuntary regulation , integrating physiological , psychological and social inputs .
studies in experimental animals have shown that vagal afferents signal peripheral sensory stimulation from the airways and lungs , and project centrally to the nucleus tractus solitarius ( nts ) with further projections between the nts and the medulla and pons . that such projections constitute a regulatory brainstem
cough centre is a concept that has been extensively pursued ; attempting to determine the specific central pathways involved in the initiation and regulation of the efferent arc of the cough reflex .
the aetiology of chronic cough has been considered in a similar manner to the aetiology of chronic pain , with elements of both peripheral and central sensitization .
most of the common causes of chronic cough , and notably the classically described  diagnostic triad of asthma , gastro - oesophageal reflux disease and postnasal drip , arise primarily through the activation of peripheral vagal afferents , but with probable central maladaptation contributing to hyper - sensitization to peripheral stimuli .
pathological impingement of the dorsal medullary region of the brainstem is recognized as a neurogenic cause of chronic cough in cases of patients with chiari i malformations and cough may be the initial symptom .
however , to our knowledge , this is the first reported case of a lymphoma around the brainstem with chronic cough as one of the first symptoms .
it is difficult to be certain as to the mechanism of chronic cough induced by this lymphoma .
it may be that the expanding mass of the dlbcl compressed nearby nerve efferents serving the cough reflex , leading to aberrant hypersentization .
however , dlbcl can be an aggressive lesion and has been reported to present with focal neurology from local invasion into nerves .
it is possible , therefore , that the chronic cough in this case was caused by tumour infiltration into nerves rather than compression .
although clearly cerebral lymphoma is a very rare cause of chronic cough , we believe that clinicians in primary and secondary care should consider rare central causes of chronic cough in cases where neurological symptoms or signs are present , or in cases where empirical treatment for the more common causes of cough fails to provide symptomatic relief .

Answer:
we report a rare case of chronic cough as the presenting symptom of a primary brainstem lesion .
 a 69-year - old gentleman presented with chronic cough followed by onset of progressive truncal ataxia , incoordination and nystagmus .
 contrast - enhanced imaging showed a midbrain lesion extending into the cerebellum , confirmed as lymphoma by stereotactic brain biopsy .
 the patient was successfully treated with chemotherapy , but his cough persists .
 we present this case to highlight the possibility of a brainstem lesion as a rare central cause of chronic cough , and suggest that the diagnosis is considered in those with concomitant neurological symptoms .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Plasma Levels of S100A4 in Portopulmonary Hypertension

Paper sections:
Introduction

Experimental models of pulmonary arterial hypertension (PAH) have implicated numerous genes in its pathogenesis. One such gene is S100A4, an intracellular calcium binding protein which causes pulmonary vascular remodeling in transgenic mice over-expressing the gene product (1). S100A4 also plays a role in tissue remodeling in lung and liver fibrogenesis (2,3) and metastatic tumor invasion (4).

PAH associated with portal hypertension, also known as portopulmonary hypertension (PPHTN), shares many pathological features with idiopathic and familial PAH (5). Approximately 5% of patients with cirrhosis being evaluated for liver transplantation have PPHTN (6–8), which may increase morbidity and mortality and greatly complicate liver transplantation (9,10).

There have been few studies of circulating biomarkers which characterize patients with PPHTN. We have previously shown that genetic variability in a S100A4 single nucleotide polymorphism (SNP) is associated with the risk of PPHTN in patients with liver disease (11). In the current study, we aimed to determine whether plasma levels of S100A4 were higher in patients with PPHTN compared to patients with advanced liver disease without evidence of PPHTN and disease-free controls.

Study Design and Study Sample

The Pulmonary Vascular Complications of Liver Disease (PVCLD) study enrolled a cohort of 536 patients evaluated for liver transplantation or pulmonary hypertension at seven centers in the United States between 2003 and 2006. The only inclusion criterion was the presence of clinical portal hypertension with or without intrinsic liver disease. We excluded patients with evidence of active infection or recent (< two weeks) gastrointestinal bleeding, or who had undergone liver or lung transplantation. Full details of the cohort are published elsewhere (12).

We performed a case-control study within the PVCLD cohort. The study sample included newly-referred patients who were evaluated with transthoracic echocardiography (routinely performed for pre-transplant evaluation) during the study period. "Prevalent" patients who met the case definition (see below) were also included. We excluded patients with significant obstructive or restrictive lung disease, as previously defined (12). The study sample also excluded patients with human immunodeficiency virus infection (which may independently cause PAH), hepatocellular carcinoma or hepatic mass (which may affect S100A4 levels), or the presence of more than moderate aortic or mitral stenosis or regurgitation or significant left ventricular dysfunction by transthoracic echocardiography (which may result in pulmonary hypertension).

Case and Control Definitions

Cases with PPHTN met the following criteria at entry into the cohort: 1) mean pulmonary artery pressure > 25 mm Hg, pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) ≤ 15 mm Hg, and pulmonary vascular resistance > 240 dynes-s•cm−5 measured by right heart catheterization, and 2) no other etiology for pulmonary hypertension. Controls met the following echocardiographic criteria at entry into the cohort: 1) right ventricular (RV) systolic pressure < 40 mm Hg (if estimable) and 2) absence of right atrial or ventricular dilation, hypertrophy, or dysfunction. "Prevalent" cases who had previously undergone evaluation and were subsequently being treated (n = 2) were also included; data from the initial evaluation (before treatment) were used for these cases. It was recommended that patients with RV systolic pressure > 50 mm Hg with abnormal RV morphology by echocardiography undergo right heart catheterization.

Assays

Plasma was isolated from centrifuged whole blood and stored at −80°C. Plasma was then thawed and S100A4 concentration was assayed by enzyme linked immunosorbent assay (ELISA) (CircuLex, Nagano, Japan). All samples were assayed in duplicate according to manufacturer's instructions (13). Plates were read on a microplate reader and analyzed with SoftMax (Molecular Devices, Toronto, Canada) for quantification. Five samples had repeat analysis for estimation of the intraclass correlation coefficient (ICC) with 95% confidence interval (95% CI). Details of S100A4 genotyping are provided elsewhere (11).

Data Analysis and Sample Size Calculation

We used Student's t-tests, Wilcoxon rank sum tests, chi-square tests, Fisher's exact tests, and Spearman's rho, as appropriate. Fourteen cases with 32 controls provided 80% power to detect a difference in plasma S100A4 levels of 0.9 standard deviations with a logistic non-parametric adjustment (α = 0.05) (14).

Results

Fourteen cases with PPHTN and 32 controls with liver disease were assayed for plasma S100A4 level and genotyped. The baseline demographics of the patients are shown in Table 1. The mean ± SD age for both cases and controls was 52 ± 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.03). There was no significant difference in the proportions of non-Hispanic whites between the two groups (p = 0.16). One patient with PPHTN was receiving bosentan and one patient was receiving intravenous epoprostenol; all other PPHTN cases were untreated at the time of assessment.

The median plasma S100A4 level was 83 ng/ml (IQR 25-271 ng/ml) for cases compared to 84 ng/ml (IQR 12-156 ng/ml) for controls (p = 0.58) (Figure 1A). Both groups had significantly higher S100A4 levels than healthy volunteers without liver disease (p < 0.05). These findings did not change significantly after adjustment for gender (Data not shown). Inter-assay reliability for plasma S100A4 was excellent (ICC = 0.99, 95%CI 0.98–1.0).

We then assessed the relationship of plasma S100A4 levels with genotype of the SNP rs743687 within the S100A4 locus. The median plasma S100A4 levels were 544 ng/ml in the one patient homozygous for the minor allele (CC), 147 ng/ml (IQR 19–405 ng/ml) in the eight heterozygous patients (CG), and 74 ng/ml (IQR 18–123 ng/ml) in the 53 patients without the minor allele (GG), consistent with a possible relationship between genotype and plasma S100A4 level (p = 0.11). (Figure 1B)

Discussion

This is the first study to examine plasma S100A4 levels in patients with PPHTN and liver disease. While there was no significant difference in S100A4 levels between cases with PPHTN and liver disease controls, both groups had significantly higher levels than healthy controls without liver disease. We examined plasma level according to SNP genotype from S100A4 which suggested that the copy number of the minor allele might correlate with the plasma S100A4 levels.

The mechanism between S100A4 and PAH in animal models and humans is not clear. Merklinger et al showed that transgenic mice overexpressing S100A4 displayed increased thickness of the internal and external lamina of the pulmonary arteries (15). The elevation in RV systolic pressure seen in response to hypoxia failed to reverse with nitric oxide in the transgenic mice. The lungs of these mice showed upregulation of fibulin-5 and elastin expression, which are essential components of the extracellular matrix that contribute to vascular remodeling (16).

SNPs within the S100A4 locus have not been assessed in regards to their effect on the activity or expression of the gene product. We showed that the level of S100A4 might correlate with the SNP genotype associated with PPHTN, although concurrent processes such as hemolysis or inflammatory changes could also raise the plasma S100A4 levels S100A4 (17,18).

We assessed the value of plasma S100A4 as a biomarker of disease and found no significant differences between liver disease patients with or without PPHTN. However, the presence of liver disease itself likely led to increased plasma S100A4, which has been shown to be a robust marker of hepatic fibrosis (2). Indeed, it is possible that the elevated plasma S100A4 levels which characterize patients with advanced liver disease could serve as the milieu which permits other clinical, environmental, neurohormonal or genetic modifiers to trigger the occurrence of PAH in this setting.

There are limitations to our study. Despite having assembled a multicenter cohort of PPHTN patients, it remains a relatively rare disease leading to a small sample size. However, this study was adequately powered to detect a less than one standard deviation difference between the groups. It is possible that cases may have been misclassified as controls based on echocardiography without confirmatory right heart catheterization. To minimize this possibility, we set very stringent echocardiographic criteria for controls which essentially rule out PPHTN in patients with endstage liver disease.(19). We only examined the correlation of one SNP within the S100A4 locus with plasma levels. It may be important to define haplotypes which could have more substantial associations with the molecular phenotype.

In summary, there were no differences in plasma S100A4 levels between PPHTN patients and controls, which were greater than those of healthy controls. Our study showed that there might be a correlation between genotype variation and plasma S100A4 level. The presence of liver disease may nonspecifically increase plasma S100A4 or the high circulating levels of S100A4 in patients with advanced liver disease could facilitate the development of PPHTN.

S100A4 level according to disease status (A) and genotype (B). Genotypes include one patient homozygous for the minor allele (CC), patients heterozygous for the minor allele (CG), and patients without the minor allele (GG). Black bar represents median plasma concentration. White box represents interquartile range.

Demographics and liver disease variables

Data are shown as mean ± standard deviation or n (%). MELD = Model for End-stage Liver Disease

Answer: We previously showed that a single nucleotide polymorphism in S100A4 was associated with developing portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes-sec \xc2\xb7 cm\xe2\x88\x925, and pulmonary capillary wedge pressure \xe2\x89\xa415 mm Hg. Controls with liver disease had right ventricular systolic pressure < 40 mm Hg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 liver disease controls. The mean age for both cases and controls was 52 \xc2\xb1 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.02). There was no difference in S100A4 levels between cases and controls (p = 0.53). Both groups had significantly higher S100A4 levels than healthy volunteers (p < 0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
it is caused by trauma , stress , sepsis , adrenal tumors , anticoagulation , hemorrhagic disorders and pregnancy .
idiopathic adrenal hematoma. the symptoms vary from subclinical to clinical , such as nausea , abdominal pain , fever and hypotension due to circulatory collapse .
adrenal tumors associated with hemorrhage primarily include pheochromocytomas , adrenocortical cancers and metastatic lesions from other organs . from a clinical perspective
, whether the lesion is benign or malignant is an important issue but is difficult to determine prior to surgery .
a 59-year - old japanese man was referred to our hospital for evaluation of a 7.0 cm mass in the posterior segment of the liver or right adrenal gland in november 2009 .
this mass was discovered when abdominal ultrasonography was obtained to evaluate a weight loss of 8 kg from may to november 2009 .
his body temperature was 37.0c , his blood pressure was 124/73 mm hg , and his pulse was regular at 67/min .
hormonal examination revealed a slightly elevated metanephrine level ( 0.35 mg / day ; normal range 0.040.19 ) .
tumor marker levels , including serum -fetoprotein , carcinoembryonic antigen and carbohydrate antigen 19 - 9 were all within normal ranges . only pivka - ii was slightly elevated at 53 mau / ml ( normal < 37 ) .
abdominal computed tomography ( ct ) demonstrated a well - demarcated , 7.0 cm lesion in either the posterior segment of the liver or in the right adrenal gland .
the peripheral region was slightly enhanced and the central part was hypovascular , indicating central necrosis ( fig .
there was no evidence of lymph node enlargement or distant metastasis . on magnetic resonance imaging ( mri ) ,
, the mass showed arterial enhancement and a ct filling defect in the right superior and inferior adrenal arteries and arterial portography , respectively ( fig .
i - meta - iodo - benzylguanidine ( mibg ) scintigraphy demonstrated no aberrant accumulation in the mass , which ruled out the possibility of a pheochromocytoma .
for the purposes of securing a definite diagnosis and treatment , an open right adrenalectomy was planned for march 2010 .
the resected specimen was 7.0  5.5 cm in size , and the cut surface of the mass was heterogeneous and dark red and white in appearance ( fig .
hematoxylin - eosin staining revealed hemorrhage , necrosis and hemosiderin deposit with normal adrenal tissue .
the patient had an uneventful postoperative course and was discharged home on postoperative day 12 .
small adrenal branches from the three main adrenal arteries form a subcapsular plexus , and the gland is drained by relatively few venules .
for example , stress increases adrenal vascularity and increases adrenal venous pressure due to vasoconstriction , resulting in intraglandular hemorrhage .
idiopathic adrenal hematomas are difficult to diagnose prior to surgery . in japan , koizumi et al .   described 14 cases of idiopathic adrenal hematomas from 1983 to 2010 .
of these 14 cases , 13 had been suspected to be adrenal tumors including malignant lesions preoperatively , but were then found to be  idiopathic adrenal hematomas on pathological examination after surgery . only 1 patient was diagnosed with an idiopathic adrenal hematoma without surgery .
the adrenal hemorrhage was not suspected to be caused by an adrenal tumor on the basis of ct , hormonal assay and mibg results , and this mass spontaneously regressed after 2 weeks .
although imaging modalities such as ct and mri are helpful in detecting adrenal hemorrhage , it is difficult to determine whether the hemorrhage is associated with tumors or not .
adrenal hemorrhage associated with pheochromocytoma ( 48% ) was the most frequently observed situation , and the second most frequently observed was a malignant lesion ( 20% ) such as adrenocortical cancer or metastasis from another organ .
hematomas derived from pseudocysts or adenomas comprised 17% of all cases . therefore , even if pheochromocytoma is ruled out by hormonal evaluations and imaging studies , the possibility that the mass may be a malignant lesion remains approximately 50% .
furthermore , the size of adrenal incidentalomas , which are adrenal gland masses discovered serendipitously on imaging , is an important factor in differentiating benign tumors from malignant lesions .
nieman   recommended routine surgical resection for adrenal incidentalomas > 4 cm in diameter without a clear - cut diagnosis . in our case , metastatic liver tumors , hemorrhaged hepatic cellular carcinoma with central necrosis and adrenal tumor were raised as differential diagnoses at the time of the initial consultation because of ring enhancement with hypovascularity on enhanced ct and a slightly elevated pivka - ii level .
subsequently , abdominal angiography revealed the origin of the mass to be the right adrenal gland .
although vital signs , laboratory data and mibg scintigraphy ruled out the possibility of a pheochromocytoma , the possibility of another malignancy could not be completely ruled out .
therefore , surgery was strongly recommended for a definite diagnosis as well as for treatment .
the reason for the patient 's weight loss and the increase in the pivka - ii in our case was not clear , but may have been related to exhaustion during the summer season from may until november that kept him from eating sufficiently .
in fact , his weight loss ceased after he consulted our hospital , and the pivka - ii value also normalized prior to surgery . in conclusion , we report herein a case of idiopathic adrenal hematoma .
an accurate diagnosis of idiopathic adrenal hemorrhage is quite difficult to make prior to surgery .
some imaging modalities are useful in generating a differential diagnosis , but if the potential for malignancy is not excluded , surgical resection should be taken into consideration .

Answer:
we report herein a case of idiopathic adrenal hematoma .
 a 59-year - old japanese man was referred to our hospital for evaluation of a 7.0 cm mass in the right upper abdominal cavity .
 the tumor was suspected to originate from either the posterior segment of the liver or the right adrenal gland .
 his chief complaint was weight loss of 8 kg over the previous 6 months .
 he had no past medical history and took no medications , including no anticoagulants .
 laboratory data were almost normal except for a slight elevation of pivka - ii .
 the origin of the tumor was found to be the adrenal gland , as angiography revealed the blood supply to the mass to derive from the right superior and inferior adrenal arteries .
 a fine needle biopsy of the lesion was unable to confirm the diagnosis .
 open right adrenalectomy was performed .
 the histopathological findings of the surgical specimen revealed a hematoma with normal adrenal tissue . in the absence of any obvious etiology , the diagnosis was idiopathic adrenal hematoma .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
dr . alexandre batista liver hemangiomas are the most common benign liver tumors . diffuse hepatic hemangiomatosis ( dhh ) is a rare disorder , usually occurring in the neonate , characterized by extensive replacement of liver parenchyma with hemangiomatous lesions .
it is frequently associated with a palpable abdominal mass and high - output heart failure , with high mortality rate in neonates .
dhh in the adult , especially without extra - hepatic involvement , is extremely rare .
hemangiomatosis differs from multiple or giant hemangiomas in that the boundary of the lesion is ill - defined , while in the latter , the liver parenchyma surrounding the lesion is compressed by a fibrous capsule forming the wall of the hemangioma .
an asymptomatic 68-year - old man was referred to our hospital due to the presence of numerous nodular hepatic lesions accidentally detected on ultrasound .
there was a history of heavy drinking ( alcohol intake around 70 - 90 g / d ) and no prior history of medication or steroid intake .
physical examination upon admission revealed diffuse hepatomegaly , with no associated cardiac murmur or leg edema .
ui / l ) . abdominal ultrasound ( us ) showed multiple ill - defined sub - centimeter hyperechoic hepatic nodules , predominately in the right lobe , with no posterior acoustic shadowing or significant through transmission and absence of high vascularity on color doppler [ figure 1 ] .
68-year - old male referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .
a ) ultrasound examination demonstrates multiple ill - defined yperechoic nodules dispersed throughout the hepatic parenchyma , mostly sub - centimeter and with right hemi - liver predominance .
countless predominantly sub - centimeter nodular lesions with low t1-weighted signal intensity ( si ) and moderately high t2-weighted si were depicted .
liver lesions showed moderately restricted diffusion , and post - contrast fat - suppressed t1-weighted images showed predominantly hypovascular features with retention of contrast in later phases .
a us - guided biopsy using an automated gun with an 18-gauge needle was performed collecting three representative fragments .
68-year - old male referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .
a ) axial fatsaturated t2-weighted image shows countless small - sized moderately bright lesions ( arrows ) .
b ) diffusion weighted image shows these lesions with high signal intensity ( b = 600 sec / mm ) ( arrows ) , which may be seen in liver hemangiomas secondary to t2 shine - through effect .
axial c ) pre - contrast and ( d - f ) post - contrast fat - saturated t1-weighted images show arterial homogeneous enhancement ( arrows , d ) , some exhibiting portal phase peripheral nodular enhancement ( arrow , e ) and late centripetal filling ( arrows , f ) .
pathology revealed endothelial - lined sinusoidal proliferation with erythrocyte content , consistent with hepatic hemangiomatosis [ figure 3 ] .
definitive diagnosis of dhh was established based on a combination of imaging and pathological findings and clinical / imaging follow - up .
two years following the diagnosis , the patient 's hepatic function and imaging findings remain stable , with no relevant associated symptoms . 68-year - old
male referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .
ultrasound guided biopsy samples stained with hematoxylin and eosin a ) 4  10 , b ) 40  10 ; c ) 40  10 ) .
reveal numerous dilated nonanastomotic vascular spaces , which were lined by flat endothelial cells and supported by fibrous tissue endothelium .
chronic inflammatory infiltrates with peri - portal distribution are also present ( black outlined asterisk , c ) .
imaging plays a vital role in the detection and characterization of multifocal liver lesions in adults .
there are numerous causes including benign and malignant neoplasms , infectious lesions , and inflammatory conditions .
the us evaluation showed multiple sub - centimeter , ill - defined , hyperechoic nodules dispersed throughout the liver parenchyma , predominantly in the right hemi - liver , with very little or no flow seen on color doppler .
the differential diagnoses included metastatic disease , multifocal nodular fatty infiltration of the liver , bile duct hamartomas ( bh ) , or other less - frequent entities such as dhh or angiosarcoma .
metastatic liver involvement usually occurs in a patient with a known extra - hepatic primary neoplasm .
small hypervascular liver metastases ( e.g. from breast or neuroendocrine tumors ) may mimic small early uniform enhancing hemangiomas ; however , these lesions tend to fade or wash out , whereas hemangiomas are more likely to maintain the si or fade toward background isointensity .
also , the majority of liver metastases shows heterogeneous or ring enhancement on the arterial phase images , confirming their definite diagnosis .
multifocal nodular fatty deposition is an unusual pattern of liver steatosis that consists of multiple round or oval fat foci randomly distributed throughout the liver .
fat deposits appear isointense or hyperintense to the liver on in - phase images , dropping si on out - of - phase images .
fat accumulation does not show restriction or shine - through effect on diffusion - weighted images .
other clues indicative of multifocal fat deposition are the lack of mass effect , stability in size over time , and contrast enhancement similar to or less than that of the surrounding liver parenchyma .
bh , also called von meyenburg complexes , originate from embryonic bile ducts that fail to involute . on ultrasound ,
bh have been described as innumerable tiny hypoechoic or hyperechoic foci measuring less than 10 mm and distributed uniformly throughout the liver , with some displaying a comet tail artifact .
differences in echogenicity may be due to the size of the dilated bile duct component , which , at a certain size , would behave like other microcystic structures . on mri
, bile duct hamartomas usually appear as multiple tiny cystic lesions , strongly hyperintense on t2-weighted images .
after gadolinium administration , some authors described a thin rim of enhancement , which correlates with the compressed liver parenchyma surrounding the lesions . internal progression or retention
it is very aggressive and sometimes may mimic hemangioma on dynamic studies , showing high si on t2-weighted images , since both tumors contain abundant blood - filled vascular spaces ; also , heterogeneous centripetal and progressive enhancement has been described .
dhh is a rare , although benign , condition that is characterized by diffuse replacement of liver parenchyma by hemangiomatous lesions .
the natural history and prognosis of hepatic hemangiomatosis are poorly understood due to its rarity .
hemangiomatosis is different from multiple or giant hemangiomas in that the boundary of the lesion is ill - defined , while in the latter , the liver parenchyma surrounding the lesion is compressed by a fibrous capsule that forms the wall of the hemangioma .
dhh can occur in all age groups , but is most frequent in the neonate where it can result in high - output cardiac failure and significant mortality .
it is usually asymptomatic in adulthood , being extremely rare when not associated with giant cavernous hemangiomas and even rarer when no other organ is affected besides the liver .
two patterns of dhh are described , the diffuse ( non - nodular ) and the nodular pattern , the former being the predominant pattern , representing approximately two - thirds of the cases .
sonographically , the liver affected by dhh appears as homogeneous hyperechoic areas with poorly defined margins ( diffuse pattern ) or a heterogeneous echo pattern with multiple discrete or coalescent small hyperechoic nodules ( multinodular pattern ) .
these nodular lesions are variable in size ( usually < 5 - 10 mm ) , appearing as countless oval or round hyperechoic nodular lesions . very little or no flow
, the areas affected by hemangiomatosis may also display a diffuse non - nodular pattern composed of tiny cystic spaces separated by numerous thin hypointense septa , creating a lattice - like appearance or a diffuse nodular pattern consisting of multiple small discrete and coalescent nodules on t2-weighted imaging .
the extremely low velocity of blood flow within hemangioma relates to the absence of flow void seen in mri imaging .
dynamic contrast - enhanced mri shows heterogeneous enhancement in these areas during the arterial phase that becomes more homogeneous during portal and delayed phase imaging .
the multinodular type , as was our case , exhibits small discrete and coalescent nodules with early homogeneous enhancement or the typical peripheral discontinuous enhancement during the arterial phase , showing uniform late retention of contrast .
in conclusion , dhh with no associated cavernous hemangiomas and without extra - hepatic involvement is an extremely rare condition . despite its rarity
, it can be suggested in adults presenting with multiple , predominantly sub - centimeter hepatic lesions demonstrating mri features of hemangiomas .
mr imaging may be superior to us and computed tomography ( ct ) for the diagnosis and is the preferable cross - sectional imaging technique for long - term follow - up .

Answer:
we present a case of a pathologically proven multinodular diffuse hepatic hemangiomatosis ( dhh ) with no extra - hepatic involvement in a 68-year - old male .
 cavernous hemangioma is the most common hepatic tumor .
 however , dhh , which is characterized by extensive replacement of liver parenchyma with hemangiomatous lesions , has been rarely reported in adults .
 the etiology and clinical course are not completely understood because of its rareness , although the diagnosis might be suggested by the magnetic resonance imaging findings .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
dichlorvos ( dimethyl-2 , 2-dichloro vinyl phosphate ) is an organophosphorous ( op ) insecticide with moderate human toxicity , used for insect control in food storage areas , greenhouses , barns and control of insects on livestock .
parenteral dichlorvos administration with suicidal intention is rarely reported in the literature . in one case report
, extensive muscle necrosis was reported following intramuscular injection of dichlorvos . in another case , following injection of dichlorvos subcutaneously in both wrists , a young patient developed compartment syndrome requiring fasciotomy . in both cases
, i describe the case of a young female patient , who developed atypical signs of op poisoning following subcutaneous injection of dichlorvos .
the present case report is about a 37-year - old , previously healthy female , who was admitted to our intensive care unit 18-h after alleged self - injection of 76% dichlorvos ( nuvos ) 3 ml in the upper left arm ( 3 times with a 1 ml insulin syringe ) . within an hour of the injections
, she had normal body temperature with heart rate of 90/min , blood pressure 110/70 mmhg , respiratory rate 14/min and pulse oximeter showing 100% saturation on room air .
no crackles were heard on chest auscultation . on the nervous system examination , she was jittery with slurred speech and normal cranial nerves .
she had hypertonia , brisk tendon reflexes , bilateral sustained ankle clonus and bilateral extensor plantar reflex .
local examination revealed a blister and a black necrotizing lesion over the anterior aspect of the left arm [ figure 1 ] .
she was rapidly atropinized with incremental boluses of atropine ( total dose 12 mg ) in next 30 min ( targeting a dry mouth ) followed by infusion of 1.8 mg / h .
pralidoxime infusion was started at 500 mg / h following a loading dose of 1000 mg over 20 min .
intravenous clindamycin ( 600 mg q 8 h ) was administered empirically for presumed local wound infection .
debridement of the wound showed predominant involvement of the subcutaneous tissue plane with minimal necrosis of the superficial fibers of biceps brachii .
initial routine laboratory investigations were unremarkable except elevated total count ( 16200/mm ) and mild respiratory alkalosis .
local skin necrosis with surrounding blisters her clinical course was complicated by respiratory arrest 9-h after hospital admission ( 27-h after the injection of dichlorovos ) leading to hypoxia and bradycardia .
arterial blood gas analysis post resuscitation showed - ph 7.28 , po2 - 36 mmhg , pco2 - 54 mmhg , hco3 - 22 mmhg .
serum choline esterase ( pseudo cholinesterase ) level of the same day showed a very low value of < 1 ku /
she could be successfully weaned off from the ventilator on day 4 . on day 5 , while on atropine infusion she was found to be delirious .
she was also noticed to have extrapyramidal manifestations including rigidity and left sided gaze preference .
in this case , other than the unusual route of administration , a number of atypical manifestations were found .
this includes relatively delayed respiratory failure and central nervous system ( cns ) manifestations with few muscarinic signs .
two independent mechanisms are thought to be responsible for respiratory failure following op insecticide poisoning  cholinergic cns depression in the early stage ( associated with other cholinergic features ) and late progressive neuromuscular transmission defect .
second mechanism is part of the syndrome described as  type ii paralysis  by wadia et al . or intermediate syndrome by senanayake and karalliedde . our patient developed respiratory arrest 27-h after exposure to dichlorovos .
in her clinical course she never had neck or proximal muscle weakness , though the clinical findings were not correlated electrophysiologically .
usually cns signs are manifested early in the course in the presence of peripheral muscarinic signs . in a large series published on neurological manifestations of op compounds , 8 of 200 patients had pyramidal tract signs in the form of only hyper - reflexia manifesting within 24 h of exposure .
all these patients were unconscious with florid cholinergic manifestations , including constricted pupils . in their original series of intermediate syndrome senanayake and karalliedde , observed hyperreflexia in one of their patients ( with flexor plantar reflex ) and even she had typical muscarinic signs .
extrapyramidal signs of op poisoning are often transient and may be missed in a sick patient . in a taiwanese series
cns manifestations ( both pyramidal tract and extrapyramidal ) were delayed and were associated with relatively scanty peripheral muscarinic signs .
possible explanation for these atypical manifestations in our patient could be route specific ( in this case subcutaneous ) effect of op compound ( dichlorovos ) causing isolated delayed cns depression , with few peripheral cholinergic signs .
animal experiments have shown route specific ( subcutaneous or intravenous ) cardiovascular and neuromuscular effect of op compounds in rats .

Answer:
current case report describes a 37-year - old female patient who was admitted to the hospital following subcutaneous injection of dichlorvos with an insulin syringe .
 the only peripheral cholinergic sign observed on admission was excessive salivation with bilateral pyramidal tract signs .
 locally she had necrosis of skin and subcutaneous tissue with surrounding blisters .
 in the subsequent course of her illness , she developed respiratory arrest requiring ventilator support .
 she also had delayed extrapyramidal manifestations .
 relevant literature is reviewed .
 possibility of route - specific , delayed predominant central nervous system effect of dichlorvos postulated .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
forty - five - year - old male shelter resident , chronic alcoholic , chronic smoker , and marijuana abuser presented to emergency department ( ed ) with complaints of intermittent fever with night sweats and productive - cough for 10 days with yellowish sputum associated with pleuritic chest pain .
he complained of generalized weakness and decreased appetite and claimed to have lost approximately 10 pounds in 2 weeks .
laboratory results showed leukocytosis of 17,000/mm with neutrophil differential of 11,200/mm ( 65% ) with band neutrophils of 10% .
chest radiograph was reported as right middle lobe consolidation but careful observation revealed a foreign body ( fb ) , likely a tooth in the right bronchus intermedius ( fig .
ct scan of chest showed a well calcified fb likely a tooth at the level of carina obstructing right intermedius bronchus and consolidation in right lower lobe indicating post - obstructive pneumonia ( fig .
2 ) . patient was admitted and prescribed intravenous antibiotics targeting gram - negative organisms and anaerobes .
deep conscious sedation was achieved by propofol infusion in the presence of an anesthesiologist and cardiothoracic surgery backup .
bronchoscopy showed tooth in right intermediate bronchus with ~75% occlusion , and purulent secretions from the right main stem ( figs .
the fb was removed successfully with rat tooth forceps ( figs . 7 and 8) .
post bronchoscopy inspection showed right main stem , bronchus intermedius , and right middle and lower lobe bronchi to be well patent .
closer view of the foreign body , identifiable as tooth in right main stem bronchus .
the aspirated tooth removed by rat tooth forceps . upon further questioning , the patient said that he did not remember having aspirated the tooth and hence the duration of aspiration could not be known .
he was discharged home on oral antibiotics a couple of days after the bronchoscopy and counseled to quit alcohol and drugs .
fba is more common in children than adults with about 80% occurring in children aged less than 15 years .
it is the fourth most common cause of unintentional injury deaths in the united states . while choking is a hazard for all ages , choking deaths peaked at age 84 in 2011 as per national safety council injury facts 2015 ( 1 ) .
fba in adults is often overlooked as a potential cause of airway obstruction especially if there is no asphyxiation .
adults with risk factors such as alcoholism , drug abuse , mental retardation , and neuromuscular conditions are predisposed to aspiration .
however , accidental aspiration in adults without the aforementioned risk factors has been described ( 25 ) . in adults ,
most common foreign bodies aspirated are food and broken fragments of teeth ( 68 ) .
ct scan is more sensitive and specific than chest radiograph in diagnosing radiolucent foreign bodies and for characterizing the attenuation of a suspected fb ( 9 ) .
unlike in children , less than half of fbs are lodged in the proximal airways in adults .
most of the fbs are lodged in the right bronchial tree , whereas in children no significant difference was seen between right and left bronchial tree ( 6 ) .
bronchoscopy for the removal of fb was introduced by gustav killian , an otolaryngologist in 1897 .
animal studies performed by zavala and rhodes ( 11 ) showed that fbr could be used to retrieve different kinds of fbs by using grasping forceps through the bronchoscope .
fbr is considered as the diagnostic test of choice for initial diagnosis of fb in adults .
the advantages of fbr over rigid bronchoscopy are that it can be performed under local anesthesia , visualization of smaller peripheral airway is better with relatively easier manipulation , and can be performed in patients with deformities of c - spine and pharynx .
it is also a relatively easy and safer procedure in experienced - hands ( 10 , 12 ) .
rigid bronchoscopy is recommended if fbr fails , if the fb is centrally located , if firmly embedded in scar tissue , and for removal of sharp objects which require maneuvering to minimize mucosal trauma ( 13 ) .
there have been several case series which have reported successful removal of foreign bodies by fbr .
cunanan ( 12 ) reported a success rate of 89% in using fbr for the removal of fb in 300 mentally retarded and physically handicapped patients .
they reported a decrease in mortality from 12 to 1% with the use of fbr over rigid bronchoscope .
they , however , attribute to the increased mortality from rigid bronchoscopy to complications of general anesthesia in patients with comorbidities .
limper and prakash had a success rate of 60% with fbr , whereas rigid bronchoscopy showed a success rate of 98% . in their experience , fbr is advantageous in distally lodged fb , in cases with cervical instability , mechanically ventilated patients , and also in removal of small fbs , which can be securely grasped with a fiberoptic bronchoscope ( 14 ) .
( 15 ) report a success rate of 97% for fb removal via fbr with low mortality and morbidity .
they also reported that granulation tissue can be removed without much bleeding ; thus , removal of fb can be achieved in a repeat fbr a week later .
( 13 ) indicate that fbr can be used to remove foreign bodies especially if they are small and peripheral and that fbr may be superior to rigid bronchoscopy for grasping tiny and far - reaching foreign bodies .
rigid bronchoscopy is recommended if fbr fails and especially if the fb is large and located in central bronchi or trachea .
however , in children who may have central , asphyxiating foreign bodies , the rigid bronchoscope under general anesthesia is preferentially indicated .
team - based approach with designated roles for team members improves the chances of a successful procedure .
anesthesia and ct surgery backup is essential . team - based analysis of the nature , location of the fb , and appropriate accessory instruments is equally necessary .
steroids can be given to minimize inflammatory changes as they may lead to difficulty in fb extraction .
orotracheal approach is preferred over nasotracheal , as it avoids fb from being lost in the nasal passages if accidently dislodged .
care should be taken to keep fb in the center of visual field and to avoid pushing fb distally into the airways .
once fb has been secured , bronchoscope , accessory instrument , and the secured fb are all withdrawn from the airway simultaneously .
rare complications of fbr are likelihood of asphyxiation from losing the fb in the subglottic area and hemoptysis ( 10 ) .
another approach is to reinsert flexible bronchoscope to push the fb into more peripheral airway thus resolving the central airway obstruction . in case of hemoptysis ,
airway can be better managed by rigid bronchoscope , but this complication is very rare if performed by trained operators .
incidence of massive hemoptysis even in patients with significant granulation tissue around the fb is extremely low ( 15 ) .
organic materials can cause severe inflammation in a short period of time and tend to absorb water with development of airway obstruction relatively earlier .
in contrast , inorganic fbs are inert , and so patients might be asymptomatic for a prolonged period ( 16 ) . grasping forceps , baskets , magnet extractors ,
yag laser , and cryoprobes are available as accessories for fb removal via flexible bronchoscope ( 10 ) .
rat tooth forceps is a type of a grasping forceps , which is particularly useful for removing hard , flat , or thin organic or inorganic foreign bodies .
these are used primarily when the fb is hard as a firm grip can be achieved .
these can not be used for the retrieval of organic friable objects which tend to fracture due to the firmness of the grip provided by these forceps ( 10 ) .
zero - tip basket is used in urological procedures like retrieval of ureteral stones . the tipless design allows close approximation to fb .
they are used to retrieve fbs lodged in distal bronchi and mobile fbs ( 16 , 17 ) .
fish net basket , a modified polypectomy snare , is useful in removing bulky fbs ( 10 ) .
magnet extractors contain flexible probe tipped with a magnet , useful for retrieval of metallic fbs ( 10 ) .
fbs embedded in granulation tissue can be removed by yag laser , which vaporizes the surrounding granulation tissue .
cryoprobe is used to freeze friable organic and small inorganic materials . freezing the foreign bodies
high index of suspicion is needed especially for high - risk patients presenting with compatible symptoms .
fbr is the initial diagnostic and therapeutic procedure recommended with low complication rates in experienced hands .
rigid bronchoscopy is performed if the flexible bronchoscopy fails or if the fb is large and centrally located , in case of significant hemoptysis and if significant granulation tissue is present with a fb which is deeply embedded .

Answer:
foreign body aspiration ( fba ) is more common in children than adults with about 80% occurring in children aged less than 15 years .
 fba in adults is often overlooked as a potential cause of airway obstruction especially if there is no asphyxiation .
 we present a case of a 45-year - old male with alcohol abuse who presented with post - obstructive pneumonia secondary to aspiration of tooth of unknown duration .
 the tooth was removed via flexible bronchoscopy ( fbr ) and we will discuss the use of fbr for foreign body ( fb ) removal , which fb can be easily removed by fbr , and the different techniques and devices used for fb removal via fbr .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Sensitive Cu2+-Cu2+ Distance Measurements in a Protein-DNA Complex by Double-Quantum Coherence ESR

Paper sections:
Introduction

Herein, we demonstrate a simple way to measure paramagnetic metal ion based nanoscale distances in proteins. The advent of Double Electron Electron Resonance (DEER)1,2 and Double Quantum Coherence (DQC)3,4 methods that measure nanometer range interspin distances have had a profound impact on the application of ESR in biological research.5–12 Most of these distance measurements are based on the methanethiolsulfonate nitroxide spin-label, which is chemically attached to the cysteine residue in proteins.13 The extension of DEER and DQC distance measurements to paramagnetic metal ions can potentially generalize the technique to many proteins that contain endogenous metal ion binding sites. However, DEER and DQC with metal ions as spin probe are challenging because of large ESR spectral width and low signal to noise ratio (SNR). Nevertheless, our group14,15 and others16–26 have made tangible progress. In principle DQC can have a high SNR per shot. This provides impetus for further research of DQC. On the other hand, the DQC signal has substantial contributions from electron-nuclear interactions between the electron spin and neighboring 14N as well as 1H nuclear spins that are present in the amino-acid coordination environment. These nuclear modulation27 effects swamp the modulation due to the electron-electron dipolar (EED) interactions and make it difficult to measure the interspin distance.

EcoRI is a 62 kDa homodimeric protein28,29 that recognizes and binds to the 5'-GAATTC-3'DNA sequence with high specificity30–32, even in the absence of metal cofactors. In the presence of Mg2+, EcoRI catalyzes cleavage of both DNA strands at this site. When Mg2+ is replaced by other metal ions the cleavage rates decrease according to the series Mg2+ ≈ Mn2+ > Co2+>> Zn2+ >> Cd2+ > Ni2+.31 Interestingly, Cu2+ is a powerful inhibitor of EcoRI catalysis.33 In order to shed light on the molecular mechanism of catalytic inhibition by Cu2+, we have recently exploited DEER based distance measurements to determine that Cu2+ binds to His114 in each subunit of EcoRI,33 at points 13 Å from the Mg2+ positions in the catalytic sites. The positions of the His114 sidechains are consequently altered, and the resulting disruption of critical protein-DNA interactions and water molecules in the catalytic centers leads to inhibition of catalysis.33

In this work we present a simple way to minimize the low frequency nuclear peaks in the DQC spectrum and resolve the dipolar interaction between two paramagnetic probes Cu2+ with high sensitivity in the complex of restriction endonuclease EcoRI with its cognate DNA.

Enzyme expression and purification

The EcoRI protein was expressed from a maltose-binding protein-EcoRI (MBP-EcoRI) fusion construct. Details for generation of the fusion gene and expression of the fusion protein are given in supporting information for reference 33. The complete EcoRI protein without extra amino acids was isolated, purified, and characterized as described in reference 34.

Cu2+-EcoRI-DNA sample preparation

A solution of EcoRI (5 μM) in the presence of fivefold molar excess of TCGCGAATTCGCG was exchanged into 30 mM N-ethylmorpholine (NEM) buffer, which contains 0.3 M NH4Cl, 10% dioxane, 30% deuterated glycerol (d8), 65% D2O (pH 8.0) and concentrated. The final concentrations of EcoRI and DNA were 380 μM and 1.5 mM, respectively. Isotopically enriched 63CuCl2 (Cambridge Isotope Labs, Inc) was added at a 4:1 molar ratio (Cu2+ : protein dimer). The sample was stored at −80°C and flash-frozen before each ESR experiment.

Electron Spin Resonance Spectroscopy

All of the pulsed ESR experiments were performed on a Bruker Elexsys 580 spectrometer at 20 K, with a MD5 resonator. The six pulse DQC-ESR was using a π/2-tp+dt-π-tp+dt-π/2-t1-π-t1-π/2-t2-π-echo sequence. A 64 step phase cycle was carried out to select the correct coherence pathway and the DQC-echo after the sixth pulse was integrated.14,35 The π/2 pulse and π pulse lengths were 8 ns (or 12 ns, 16 ns and 20 ns) and 16 ns (or 24 ns, 32 ns and 40 ns), respectively. The interval tp was incremented from 80 ns with a stepsize of 8 ns, for a total of 360 points. The interval t1 was 80 ns and t2 was 200 ns. The shot repetition time was 5 ms and all the DQC time domain data were averaged for 24 scans. Each DQC experiment was done at 3350 G where the maximum echo signal was observed. Details of the DEER experiment are given in supporting information and reference 33.

Results and Discussion

Figure 1 shows the Cu2+-DQC data obtained at the g⊥ position of the Cu2+ ESR absorption spectrum. The lengths of the π pulse were 16 ns (black solid line) and 40 ns (grey solid line), respectively.

The two spectra in Figure 1b with different length of π pulse clearly contain peaks that can be attributed to the 14N-nuclear modulations in the 0–5 MHz region14 as well as the 1H-nuclear peaks at ~14 MHz. For the purpose of nanoscale distance measurements the 0–5 MHz 14N-nuclear peaks are particularly problematic, since the EED interaction is in this region. Interestingly, the intensity of the peak at ~1.46 MHz in the DQC spectrum (Figure 1b) with 40 ns π pulse is much lower compared to the spectrum with 16 ns π pulse. With shorter π pulse, e. g., 16 ns, the spectral excitation probability of the DQC EED interaction is about 0.16.35 With the longer π pulse of 40 ns, the spectral excitation probability of the DQC EED interaction is about 0.04.35 It is very clear that longer π pulse cannot substantially populate the double quantum coherence of EED interaction. However, the nuclear hyperfine and quadrupole transitions are weakly sensitive to the length of π pulse.27 This suggests that 1.46 MHz peak might originate from the Cu2+-EED interaction.

Since the experimental DQC signal is a multiplication of the EED and the nuclear signals, division of the π=16 ns DQC data by the π=40 ns DQC data may suppress the nuclear signals and resolve the EED signal.14,35
Figure 2a shows the comparison of the DQC time domain data, after dividing the π=16 ns signal by the π=40 ns signal (black solid line), with the DEER data after subtraction of the homogeneous background (grey solid line).33 The modulation periods of the two time domain traces are comparable. In this analysis, the DQC signal with 40 ns π pulse was empirically chosen for division – the data with other choices are shown in the Supporting Information. The data acquisition time of DQC (including two traces) and DEER are ~50 hrs and ~43 hrs, respectively. The data collection time in DQC can be reduced by implementation of on-board phase cycling.

The DQC spectrum after division, shown in Figure 2b (black solid line), clearly resolves the major peak at ~1.46 MHz, which is consistent with the DEER data (Figure 2b, grey solid line). Nevertheless, the DQC spectrum is narrower than the DEER spectrum. In the experimental DQC data, there might be some small residual peaks from electron-14N interactions that occur at ~3 MHz.

Figure 2 also shows the simulated DQC data (black dotted line). Based on the best fitting of the DQC time domain data shown in Figure 2, we obtained a most probable Cu2+-Cu2+ distance of ~35 Å with a standard deviation of 1 Å (Figure 2b, black solid line inset). This result is consistent with our observation from DEER experiments (Figure 2b, red dotted line inset). The simulated DQC spectrum is in accord with the dominant peak obtained in the experiment, although the DQC data is narrower.33 Details of the simulations are provided in the Supporting Information. It is likely that in DQC a narrower range of orientations is selected because the microwave pulses have a finite coverage. Despite this, the signal to noise ratio per shot in DQC is high (cf. figure caption in Figure 2 and Supporting Information).

Conclusions

We have clearly shown here that metal ion based nanometer range distance can be measured by DQC. DEER has a significant advantage due to the ease of implementation on commercial instrument. Nevertheless, the DQC data have high SNR per shot. Further improvements can be made by the use of narrower pulse lengths35 and by understanding the role of orientational effects in such DQC measurements.15,36

Answer: Double Quantum Coherence (DQC) ESR spectroscopy is applied to measure the Cu2+-Cu2+ distance in the EcoRI-DNA complex. A simple method is proposed to reduce the contribution of nuclear hyperfine and quadrupole interactions to such data. The effects of such interactions between the electron spin of Cu2+ and neighboring nuclei on the DQC data, make it difficult to measure the nanometer range interspin distance. The DQC data is in good agreement with results obtained by Double Electron Electron Resonance (DEER) spectroscopy. At the same time, the signal to noise ratio per shot in DQC is high. Taken together, these results provide impetus for further development of paramagnetic metal ion-based DQC techniques.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:

 focal epilepsies account for about two - thirds of all adult epilepsy patients , and temporal lobe epilepsy ( tle ) is the most common type of focal epilepsy ( 1,2 ) .
temporal lobe epilepsy is subcategorized as mesial ( i.e. , amygdalohippocampal ) and neocortical ( i.e. , lateral ) temporal .
mesial temporal lobe epilepsy ( mtle ) with hippocampal sclerosis ( hs ) is one of the most common types of epilepsy referred for surgical treatment ; it is often refractory to antiepileptic drugs ( aeds ) , but responds favorably to surgery ( 1,4 ) .
patients with mtle - hs and intractable seizures often experience progressive behavioral changes including increasing memory deficit with the passage of time .
in addition , surgical outcome may be worse with longer duration of epilepsy or increasing age at surgery , which suggests that mtle - hs is a progressive disorder ( 5 ) .
therefore , early detection of this syndrome and its distinction from other tle syndromes has important practical implications with regard to planning an optimal treatment strategy for the affected patient .

 in the current study
, we tried to compare the clinical characteristics of patients with mtle - hs with those who had tle due to other etiologies in order to identify potentially differentiating clinical characteristics between these two groups of patients .

 in this retrospective analytic study all patients with a clinical diagnosis of tle were recruited in an outpatient epilepsy clinic at shiraz university of medical sciences , which is the only referral epilepsy clinic in south iran .
the diagnosis of tle was made exclusively by one epileptologist working at this institution ( the first author ) and based on clinical grounds ( semiology ) , electroencephalographic ( eeg ) findings and imaging , such as magnetic resonance imaging ( mri ) .
all patients were followed up by the epileptologist at our institution for at least one year ( i.e. , until may 2014 ) .
routine eeg was requested for all patients at the time of referral . in difficult - to - diagnose or
difficult - to- treat patients we often order video - eeg monitoring to ascertain the diagnosis and formulate an individualized treatment plan , accordingly .
for all patients , a 1.5 tesla brain mri ( epilepsy protocol ) was performed .

we classified patients as having mts ( if they had clear signs of mesial temporal sclerosis and/or atrophy in their mri ) and those who had any other mri abnormality .
patients with dual pathology ( i.e. , mesial temporal sclerosis associated with other structural lesions ) were excluded from the study .

age , gender , age at seizure onset ( i.e. , the first afebrile seizure ) , seizure type(s ) , epilepsy risk factors ( including pregnancy complications , history of febrile seizure , cns infection , significant head trauma , positive family history of epilepsy ) , eeg findings ( the most informative eeg ) , and mri findings of all patients were registered routinely .
seizure types were categorized as generalized tonic clonic seizures ( gtcs ) , complex partial seizures ( cps ) and auras .
pearson chi - square , fisher 's exact , and mann - whitney u tests were used for statistical analyses .

 until may 2014 , 2890 patients with epilepsy were registered at our epilepsy clinic .
four hundred twenty - seven patients ( 14.7% ) were diagnosed as having tle . of these ,
174 patients were eligible to enter the study ( 105 patients with mtle - hs and 69 patients with tle due to other etiologies ) .
demographic and clinical characteristics of patients with mtle - hs and those who had tle due to other etiologies are shown and compared in table 1 .
frequency of seizure types ( i.e. , gtcs vs. cps vs. auras ) was not significantly different between these two groups ( table 1 ) .
specific types of auras were significantly different between these two groups ( table 1 ) , however most auras were reported by both groups , similarly .
epilepsy risk factors were reported to be as follows ( mtle - hs vs. others ) : parental consanguinity in 41 / 30 ( p= 0.6 ) , family history of epilepsy in 18 / 10 ( p= 0.6 ) , significant head trauma in 15 / 7 ( p= 0.4 ) , cns infection in 2 / 2 ( p= 0.6 ) and pregnancy complications in 2 / 3 ( p= 0.3 ) .

mtle - hs : mesial temporal lobe epilepsy ( mtle ) with hippocampal sclerosis ( hs ) .

video - eeg monitoring was available in 155 patients ; and 19 patients had a routine eeg only .
eleven patients ( 10.4% ) with mtle - hs and four ( 5.8% ) with other etiologies had normal eeg ( p= 0.2 ) .
right sided , left sided or bilateral focal epileptiform discharges ( i.e. , temporal seizures , spikes or sharp waves ) were observed in 36 , 38 , and 20 patients with mtle - hs and 31 , 21 and 13 patients with other etiologies , respectively ( p= 0.4 ) . focal polymorphic delta activity or temporal intermittent rhythmic delta activity ( tirda ) was seen in 60 and 7 patients with mtle - hs , respectively .
these figures were 32 and 4 in patients with other etiologies ( p= 0.3 ) .

magnetic resonance imaging ( mri ) in patients with other etiologies ( non- mtle - hs group ) showed temporal lobe tumors in 27 patients ( 39.1% ) , non - specific white matter mri abnormalities in 11 ( 15.9% ) , cavernoma in seven ( 10.1% ) , sequels of head injury in six ( 8.7% ) , arachnoid cysts in five ( 7.2% ) and other etiologies in 13 ( 18.8% ) patients .
twelve patients had dual pathology ( mesial temporal sclerosis in addition to another lesion ) .

 mesial temporal lobe epilepsy with hippocampal sclerosis is a common type of epilepsy referred for surgical treatment due to medical refractoriness . as a matter of fact
however , it has been suggested that early surgical intervention after seizure onset is an important precondition for achieving seizure - free status after surgery ( 6 ) .
therefore , early detection of this syndrome has important practical implications with regard to planning an optimal treatment strategy for the affected patient , particularly those with medically - refractory seizures .

 in the current study
, we observed that earlier age at epilepsy onset ( i.e. , teenagers compared to young adulthood ) , a past history of febrile seizures and reporting affective auras ( e.g. , fear , anxiety , depression , joy , and anger ) were commonly seen in patients with mtle - hs , while auditory auras were more frequently reported by those with tle due to other etiologies .
in previous studies dominantly represented by patients with hs on mri , it has been observed that age at onset is variable ( 7 ) .
the finding that age at onset is a potential clinical variable to distinguish mtle - hs from tle due to other etiologies should be further explored in future studies .

several studies have shown a significant relationship between a history of febrile seizures in early childhood and mesial temporal sclerosis . in one study , it was observed that hippocampal t2 hyperintensity after febrile status epilepticus represents acute injury often evolving to a radiological appearance of hs after one year ( 8) . having a past history of febrile seizure is a useful historical clue in favor of mtle - hs compared to tle due to other etiologies .

 as the first ictal symptoms
, auras can provide important localizing and lateralizing information useful in determining the location of the epileptogenic zone ( 9 ) .
the observation that , affective auras ( e.g. , fear , anxiety , depression , joy , and anger ) were commonly seen in patients with mtle - hs , while auditory auras were more frequent among those with tle due to other etiologies , has very important clinical implications . in one study ,
the authors examined the relationship between presence of different types of auras and post - surgical outcomes in 157 patients with medically intractable mesial temporal lobe epilepsy ( mtle ) with unilateral hippocampal sclerosis ( hs ) .
the occurrence of multiple auras was not associated with post - surgical outcome ( p = 0.7 ) .
but , the presence of extratemporal auras ( e.g. , somatosensory , visual and dysphasic auras ) was significantly higher in patients with poor outcome ( 10 ) . designing future studies to investigate the relationship between presence of mesial temporal lobe auras ( e.g. , psychic symptoms , cognitive and affective auras , autonomic auras such as epigastric sensation , olfactory and gustatory auras ) versus lateral temporal lobe auras ( e.g. , vertiginous and auditory auras ) and surgery outcome in patients with mtle - hs is necessary .

 the mainstay for making a correct diagnosis , when evaluating a patient with seizure , is having a standardized approach , particularly with regard to taking a detailed clinical history .
one may find important clues in the clinical history ( e.g. , age at onset , detailed seizure description and past history ) to make a syndromic diagnosis .
the syndromic diagnosis forms the basis for the treating physician to decide upon an appropriate management plan .

 this was a clinic - based series and may not represent the full spectrum of tles .

 we would like to thank neurosciences research center , shiraz university of medical sciences , shiraz , iran for supporting this study .

Answer:
background : this study compares the clinical characteristics of patients with mesial temporal lobe
 epilepsy with hippocampal sclerosis ( mtle - hs ) with those who have temporal lobe epilepsy ( tle )
 due to other etiologies
 .

 methods : in this retrospective study all patients with a clinical diagnosis of tle were recruited in a
 referral outpatient epilepsy clinic at shiraz university of medical sciences from september 2008 to
 may 2013 .
 we classified the patients with tle as having mesial temporal sclerosis if they had clear
 signs of mesial temporal sclerosis and/or atrophy in their mri and others who had any other mri
 abnormality .

 results : a total of 174 patients were studied ( including 105 patients with mtle - hs and 69 patients
 with tle due to other etiologies ) .
 frequency of seizure types was not significantly different
 between these two groups .
 earlier age at epilepsy onset ( p= 0.005 ) , a past history of febrile seizures
 ( p= 0.010 ) and presence of affective auras ( p= 0.008 ) were commonly seen in patients with mtlehs ,
 while auditory auras ( p= 0.020 ) were more frequent in those with tle due to other etiologies .

 conclusion : the mainstay for making a correct diagnosis , when evaluating a patient with seizure ,
 is having a standardized approach , particularly with regard to taking a detailed clinical history .
 one
 may find important clues in the clinical history ( e.g. , age at disease onset , detailed seizure description
 and past history ) to make a correct diagnosis .