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:
they are present in 10 to 55% of cases  trotter , konarik , reaching 23% of cases in the free part of the limb - valsecchi .
the brachial artery begins at the distal border of the tendon of the teres major muscle and ends close to the elbow joint .
frequently the brachial artery divides more proximally into radial , ulnar and common interosseous arteries .
some of the common variations of the brachial artery are present in the superficial brachial artery of the arm .
this artery moves together with the median nerve and continues as the radial artery twice as frequently , when compared to the ulnar artery ; less frequently it continues as both arteries - bergman et al . .
the brachial artery is used in routine procedures , such as blood pressure recordings and arteriography of different parts of the body .
variation in the proximal and distal branching pattern of brachial artery is important for vascular surgeons .
the superficial palmar arch is formed predominantly by the ulnar artery , with a contribution from the superficial palmar branch of the radial artery .
according to the classic description ( goss , bouchet & cuilleret , anastomosis among the ulnar and radiopalmar arteries form the superficial palmar arch .
adachi   thinks that the superficial palmar arch has an ulnar - predominant formation , which he calls the ulnar - type ( 59% of cases ) .
coleman & anson   developed a classification , in which the superficial palmar arch is formed in 78.46% of cases .
the hand surgeon needs to know about the existence and healthy functioning of the palmar arch and the types of variations .
this is very important before surgical procedures such as arterial repairs or a vascular graft .
the main purpose of this case report is to describe the blood supply variations in the upper limb and to analyze the actual formation of the superficial palmar arch in the palm region .
the case was described after a routine dissection during the anatomy class with students from the department of anatomy , histology and pathology at the medical faculty of the university of sofia .
the 75 years old male cadaver was fixed with the formaldehyde method . at the left upper limb
were observed and documented vascular variations of the brachial artery and composition of the superficial artery arc .
it became possible to trace the brachial artery after the removal of subcutaneous adipose tissue and venous branches .
this division was approximately at 10.4 cm from the beginning of brachial artery ( figure 1 ) .
this superficial brachial artery became radial and was not involved in the formation of the palm arch .
the superficial brachial artery pathway was closer to the median nerve in the first several centimeters , but after that it strayed on the lateral position and passed through the lateral sulcus of the cubital region . in this region , the brachial artery together with the ulnar and median nerve passes along the medial sulcus .
the brachial artery on the forearm gives the beginning of median , common interosseous and ulnar branches approximately 4 cm after the cubital region ( figure 2 ) .
the pathway of the median artery is accompanied by the median nerve and on the distal forearm part composes the superficial artery arch .
this structure is an anastomosis between the median and ulnar artery ( figure 3 ) .
the brachial artery persisted in the brachial region without the superficial branch and on the proximal forearm was divided by the common interosseous , ulnar and radial artery .
the superficial palmar arch was the connection between the ulnar and the radial artery in this case .
at the time of embryo development , the deep artery system of the upper limbs originates from the primitive axial artery and superficial brachial artery ( muller , senior , rodriguez - baeza a , et al . ) .
the axillary , brachial and interosseous arteries are the main branches of the primitive axial artery .
the brachial and axillary arteries merge with the help of the superficial brachial artery in the proximal region of the arm .
distally , the superficial brachial artery anastomoses with the brachial artery by medial branch of the superficial brachial artery .
the derivatives of the forearm artery are median ( colligate with the deep branch of the radial artery , the branch of the primitive avail artery ) and the ulnar artery , which anastomoses with the terminal trunk of the primitive axial artery ( ulnar system ) .
according to singer , because of these anastomoses , there is an increase in the local blood flow and involution of the proximal segment of the superficial brachial artery . in this case
it is possible for the ulnar artery to arise directly from the primitive axial artery .
this is one of the common morphological and genetic alterations found in the variations of the upper limb blood supply .
changes in the origin or involution of these segments are the cause of morphogenetic alterations found in the anatomy of the arteries of the upper limbs .
the position of the high bifurcation of the brachial artery relative to the biepicondylar line of the elbow and the pathway of median nerve are observed very well .
most significant research of detailed arterial variations of the upper limb are articles by adachi , bouchet & cuilleret   coleman & anson ; according to these authors summative of more than a thousand cases , 18.5% are anatomical variations , 77% being cases with high origin of radial artery , while the ulnar artery was a persisting 12.2% of the variations .
described a case of arterial malformation in an old female cadaver , whereby the radial artery was formed in the axillary artery with a superficial path in an anterior region of the arm , converging deeply at the brachial artery in the cubital fossa . according to pelin et al .
the high origin of the radial artery is 14.27% in dissections of cadavers and 9.75% in an angiographic study . in some cases
described one case of triple branches of brachial artery on the 4.9 cm , which began at the brachial artery and formed the radial , ulnar and superior collateral ulnar arteries .
another interesting case described the trifurcation of the brachial artery occurring in the proximal third of the forearm and composing the radial , ulnar and common interosseous branches , which passed into the pronator teres muscle .
the presence of the superficial brachial artery originating in the axillary artery was observed in 12.2 % of 304 korean cadavers .
the superficial palmar arch ( spa ) is the main vascular structure of the palm region and is localized beneath the same name aponeurosis .
coleman ss , anson bj   found a 37% chance occurrence of a complete arch , formed entirely by the ulnar artery .
they observed more than 650 specimens , while exploring the spa , and found out that the ulnar artery joined a large vessel from the deep palmar arch at the base of the thenar region .
the median artery ( ma ) of the antebrachial forearm region is the most important vessel at the time of embryo development .
it maintains the superficial palmar arch ( spa ) , while the radial and ulnar arteries are developing .
when the main arteries of this region are fully developed ( radial and ulnar arteries ) , the median artery disappears . in very rare cases ,
after that the ma may form the spa ( claassen h , schmitt o , wree a . due to its close proximity to the median , the median artery nerve can be involved in several clinical disorders such as carpal tunnel syndrome , anterior interosseous nerve syndrome and pronator syndrome . in view of the described variations
, we believe that the knowledge of this unusual blood supply is extremely important , especially for the clinical or surgical practice .

Answer:
variations of arterial patterns in the upper limb have represented the most common subject of vascular anatomy .
 different types of artery branching pattern of the upper limb are very important for orthopedists in angiographic and microvascular surgical practice.the brachial artery ( ba ) is the most important vessel in the normal vascular anatomy of the upper limb .
 the classical pattern of the palmar hand region distribution shows the superficial palmar arch .
 normally this arch is formed by the superficial branch of the ulnar artery and completed on the lateral side by one of these arteries : the superficial palmar branch of the radial artery , the princeps pollicis artery , the superficial palmar branch of the radial artery or the median artery.after the routine dissection of the right upper limb of an adult male cadaver , we found a very rare variant of the superficial arch artery  a division in a higher level brachial artery .
 we found this division at 10.4 cm from the beginning of the brachial artery .
 this superficial brachial artery became a radial artery and was not involved in the formation of the palm arch . in the forearm region ,
 the artery variant was present with the median artery and the ulnar artery , which form the superficial palm arch .


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:
adenomyosis is a common gynecological condition that is characterized by ingrowths of the endometrial cells into the myometrium .
adenomyosis and leiomyoma are benign conditions that are often responsible for uterine enlargement , menorrhagia , anemia , and infertility .
adenomyosis or internal endometriosis may occur as a result of increased overgrowth of the endometrium with invasion of the underlying myometrium or the displacement of the endometrium during pregnancy , delivery , endometrial curettage , cesarean section , myomectomy , or metroplasty .
because of its similarities to leiomyoma , it can be difficult in some cases to accurately diagnose adenomyosis by ultrasound .
most gynecologists will consider conservative medical treatment more often for adenomyosis only , while surgical options will be chosen frequently for leiomyoma or combined adenomyosis and leiomyoma , especially in large uteri .
the three most common methods of clinical diagnosis of adenomyosis are magnetic resonance imaging ( mri ) , transabdominal ultrasonography ( tas ) , and transvaginal ultrasonography ( tvs ) .
there is limited diagnostic capacity with tas , while tvs is a more feasible option .
moreover , tvs is also much more cost effective than mri and is generally more readily available in the office to most practicing gynecologists .
the aim of this retrospective study was to determine the accuracy , sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of tvs in the diagnosis of adenomyosis and leiomyoma confirmed by postsurgical histopathological findings .
the importance of an accurate noninvasive diagnostic method like ultrasound for adenomyosis , leiomyoma , or combined is an ongoing need in the gynecological community .
this was an institutional review board ( irb ) approved retrospective consecutive case series study . from november 2006
to may 2012 , patients underwent surgery for the treatment of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma .
diagnostic criteria of uterine adenomyosis include two of the five sonographic features on tvs : ( 1 ) no distinction of the endometrial - myometrial junction ; ( 2 ) asymmetry of the anterior and posterior myometrium ; ( 3 ) subendometrial myometrial striations ; ( 4 ) myometrial cysts and fibrosis ; and ( 5 ) heterogeneous myometrial echotexture . diagnostic criteria of uterine leiomyoma include two of the five sonographic features on tvs : ( 1 ) clear demarcation of the tumor margin ; ( 2 ) whorly appearance of the tumor content ; ( 3 ) the presence of blood vessels ( by color doppler ) surrounding the tumor ; ( 4 ) irregularities of the uterine surface ( subserous and intramural tumors ) ; and ( 5 ) irregularities of the endometrial surface ( submucous tumors type 1 and 2 ) .
symptomatic patients diagnosed with adenomyosis and leiomyoma via tvs underwent myomectomy with excision of the surrounding myometrium which presumably contained adenomyosis . following surgery , a histopathological examination was performed by the hospital pathologists .
student 's t - tests were used for parametric continuous variables ; and the chi - square or fisher 's exact test , where suitable , was used for categorical variables .
sensitivity , specificity , npv , ppv , positive and negative likelihood ratios , and accuracy were determined for ultrasound findings as they corresponded to the final histopathological diagnosis .
from november 2006 to may 2012 , 163 patients underwent surgery for the treatment of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma .
one hundred and twenty - three patients were diagnosed with adenomyosis , and 134 patients were diagnosed with leiomyoma .
twenty - nine patients were diagnosed with adenomyosis only , 40 patients were diagnosed with leiomyoma only , and 94 patients were diagnosed with combined adenomyosis and leiomyoma , as illustrated in figure 1 .
patient diagnosis groups one hundred and thirty patients diagnosed with adenomyosis or combined adenomyosis and leiomyoma via tvs underwent hysterectomy .
the mean age was 43.7 years with a standard deviation ( sd ) of 6.7 years and median of 43 years .
there was no significant difference in the mean age , weight , height , gravidity , and parity of the patient diagnosis groups .
patient characteristics for 163 females who underwent hysterectomy or myomectomy between 2006 and 2012 of the 123 patients ( 75.46% ) who were positively diagnosed with adenomyosis , 93 of the patients ( 75.61% ppv ) diagnoses were confirmed by the histopathological findings .
histopathological reports found 23 ( 57.50% npv ) confirmed negative diagnoses and 17 ( 42.50% ) positive findings .
the sensitivity of tvs in the diagnosis of adenomyosis was 84.55% ( 95% ci 76.4 - 90.7 , p < 0.0001 ) and the specificity was 43.40% ( 95% ci 29.8 - 57.7 , p = 0.41 ) .
table 2 shows the sensitivities , specificities , ppvs , npvs , and accuracy for each of the initial tvs diagnoses .
this could be explained by the difficulty to diagnose adenomyosis in patients with other intrauterine abnormalities or conditions .
patients positively diagnosed with adenomyosis via tvs are 1.49 ( 95% ci 1.16 - 1.92 , p < 0.002 ) times more likely to have the condition .
conversely , patients negatively diagnosed with adenomyosis via tvs are 2.81 ( 95% ci 1.65 - 4.79 , p = 0.0002 ) times less likely to have the condition .
number of patients , positive and negative predictive values , sensitivity , specificity , and accuracy of transvaginal ultrasound for initial diagnosis with histopathological correlation ( n=107 ) one hundred and thirty - four patients ( 82.21% ) were diagnosed with leiomyoma and 29 patients ( 17.79% ) were negative for leiomyoma upon the initial tvs .
of the 134 patients diagnosed with leiomyoma , 133 ( 99.25% ppv ) had a confirmed diagnosis represented in their postsurgical pathology report and one patient 's ( 0.75% ) pathology report did not confirm the diagnosis .
of the 29 patients whose tvs diagnosis was negative for leiomyoma , 24 ( 82.76% ) patients histopathological findings were also negative , and five patients ( 17.24% ) had a positive histopathological diagnosis .
the corresponding sensitivity and specificity of tvs as a diagnostic test for leiomyoma was 96.38% ( 95% ci 91.75 - 98.81 ) and 96.00% ( 95% ci 79.65 - 99.90 ) , respectively .
patients with a positive diagnosis of leiomyoma via tvs are 24.09 times ( 95% ci 35.30 - 164.45 , p = 0.001 ) more likely to have leiomyoma .
patients with a negative diagnosis of leiomyoma via tvs are 26.53 times ( 95% ci 11.16 - 62.89 , p < 0.0001 ) less likely to have leiomyoma .
for the statistical calculations of adenomyosis and leiomyoma as coexisting conditions , analyses were performed excluding the patients who were diagnosed with a singular condition .
these patients were classified as  negative  solely for the purpose of calculations regarding the combined condition . of the 94 patients ( 57.67% ) that were positively diagnosed with combined adenomyosis and leiomyoma ,
70 ( 74.47% ppv ) had histopathological confirmation of both conditions and 24 patients ( 25.53% ) did not have evidence of both conditions in their post - surgical pathology report .
sixty - nine ( 42.33% ) patients had a negative tvs diagnosis for combined adenomyosis and leiomyoma , and 49 ( 71.01% npv ) had histopathological confirmation of the negative diagnosis . however , 20 patients ( 28.99% ) had a positive histopathological diagnosis for both adenomyosis and leiomyoma . the sensitivity and specificity of tvs in the diagnosis of combined adenomyosis and leiomyoma was 77.78 ( 95% ci 67.79 - 85.87 ) and 67.12% ( 95% ci 55.13 - 77.67 ) , respectively .
patients who obtained a positive tvs diagnosis are 2.37 times ( 95% ci 1.67 - 3.34 , p < 0.0001 ) more likely to be diagnosed with combined adenomyosis and leiomyoma .
alternatively , patients who are negatively diagnosed with adenomyosis and leiomyoma via tvs are 3.02 times ( 95% ci 1.99 - 4.59 , p < 0.0001 ) less likely to be diagnosed with combined adenomyosis and leiomyoma .
adenomyosis is a gynecological disorder that is characterized by the overgrowth of the endometrium into the underlying myometrium .
the difficulty in diagnosing adenomyosis clinically is due to the lack of strong positive pathognomonic signs and/or clinical findings .
the explanation for this wide range of values , as described by azziz , is the result of differences in the histological criteria for the diagnosis of adenomyosis , the care of which the pathologic specimens are handled , and the number of blocks of sampling specimens taken .
various measures of accuracy were calculated for the diagnosis of adenomyosis , leiomyoma , and combined adenomyosis and leiomyoma .
table 3 shows a comparison of sensitivity , specificity , ppv , and npv of this study with several previous studies that investigated the diagnosis of adenomyosis .
it is important to note that the mean number of patients included in the 13 previous studies in table 3 is 76.8 patients ; however , this study utilized 163 patients in the analyses .
along with differences in inclusion criteria , ultrasound equipment , and/or the differences in the criteria to diagnose adenomyosis , the larger sample size could contribute to the difference in results .
the sensitivity and specificity of tvs for the diagnosis of adenomyosis in this study was 84.55 and 43.40% , respectively .
the associated p value for the specificity was not significant , suggesting tvs as a diagnostic tool is sensitive , but not specific in the diagnosis of adenomyosis .
the sensitivity in this study is similar to those previously reported in table 3 , but the specificity is the lowest of those reported .
this could be due to the difficulty in diagnosing adenomyosis in the presence of other uterine abnormalities and conditions , especially uterine leiomyomata that may distort the uterus .
patients that were diagnosed with multiple intrauterine conditions were not excluded from this study , since the principle inclusion criteria was patients who underwent hysterectomy or myomectomy and a preoperative tvs .
sensitivity , specificity , positive and negative predictive values of tvs for the diagnosis of adenomyosis from previous series compared with this series the sensitivity of tvs for the diagnosis of leiomyoma was 96.38% and the specificity was 96.00% , which is similar to that of a previous study .
the sensitivity for the diagnosis of combined adenomyosis and leiomyoma was 77.78% , and the specificity was 67.12% .
it was accurate , sensitive , and specific in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma .
tvs was both accurate and sensitive in the diagnosis of adenomyosis , but not specific .
moreover , tvs is cost effective and readily available in the office to the majority of practicing gynecologists .
this study demonstrated that tvs is a valuable noninvasive method that should be utilized in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma .

Answer:
objective : to evaluate the accuracy , sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of the diagnosis of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma by the use of transvaginal ultrasonography ( tvs ) compared to the histopathological findings.subjects and methods : this is a retrospective study of patients with a preoperative tvs diagnosis of adenomyosis , leiomyoma , or combined .
 patients diagnosed with adenomyosis or combined adenomyosis and leiomyoma via tvs underwent hysterectomy .
 symptomatic patients diagnosed with adenomyosis and leiomyoma via tvs underwent myomectomy with excision of the surrounding myometrium which contained possible adenomyosis . following surgery , a histopathological examination was performed by the hospital pathologists .
 the microscopic diagnosis of the specimen was recorded.results:tvs diagnosis of adenomyosis was sensitive but not specific .
 tvs was sensitive , specific , and accurate in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma.conclusion:this study demonstrated that tvs is a valuable noninvasive method that should be utilized in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma .
 tvs is sensitive , but is not specific in the diagnosis of adenomyosis only .


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:
systemic thrombolytic therapy with recombinant tissue plasminogen activator ( rt - pa ) , intra - arterial thrombolytic therapy , and mechanical revascularization are therapeutic options in acute ischemic stroke ( ais ) in adults [ 1 , 2 , 3 ] . published experience in ais in childhood
a previously healthy 14-year - old boy was admitted with acute onset of severe left hemiparesis with a national institute of health stroke scale ( nihss ) score of 12 .
there was no prior history of trauma , infection or family history of migraine or other cerebrovascular disease , but the boy was complaining of frontal headache over the last 2 weeks .
intravenous rt - pa infusion ( 0.9 mg / kg ) was started 3 h after onset of symptoms but was discontinued after 2/3 of dosage because of serious neurological deterioration .
we immediately performed an mri which revealed acute ischemic lesions in both territories of the anterior cerebral arteries ( aca ) and the left middle cerebral artery ( mca ) .
mr angiography ( mra ) showed the right aca without flow signal , the left internal carotid artery ( ica ) with an intracranial stenosis , and several mca branches with lack of flow ( fig .
several differential diagnoses were considered : dissection , isolated cerebral vasculitis , arterial spasms , infection , multiple cardiac embolism , and intoxication .
screening for heroin , amphetamine , ecstasy , ethanol , and cocaine in blood and urine was negative .
a previously healthy 10-year - old boy was admitted with acute severe left hemiparesis ( nihss 16 ) and headache after jumping on a trampoline .
there was no history of infection or family history of migraine or other cerebrovascular disease .
mri revealed an acute ischemic lesion in the right mca territory , occlusion of the right ica , and a thrombus in the right mca ( fig .
2 ) . intravenous rt - pa infusion ( 0.9 mg / kg ) was started within 3 h after onset of symptoms .
as no improvement was observed at the end of the rt - pa infusion , mechanical revascularization was performed .
a goose neck snare was passed through the thrombus which was partially fragmented and finally dissolved .
flow was established in the right mca and the branches 5 h after the onset of stroke ( fig .
the potential trauma ( bouncing trampoline ) and thrombus formation in the ica made an intima dissection most likely , but could not be confirmed by angiography . no stent was used and platelet inhibition was started the next day .
transesophageal echocardiography and routine blood samples , including extensive coagulation tests , were all normal .
the boy improved ( nihss 13 the next day ) and was transferred to the department of pediatric neurorehabilitation on day 3 . at 3 month
, he was back to school , but was still suffering a slight hemiparesis ( modified rankin scale ( mrs ) 2 ) .
a previously healthy 14-year - old boy was admitted with acute onset of severe left hemiparesis with a national institute of health stroke scale ( nihss ) score of 12 .
there was no prior history of trauma , infection or family history of migraine or other cerebrovascular disease , but the boy was complaining of frontal headache over the last 2 weeks .
intravenous rt - pa infusion ( 0.9 mg / kg ) was started 3 h after onset of symptoms but was discontinued after 2/3 of dosage because of serious neurological deterioration .
we immediately performed an mri which revealed acute ischemic lesions in both territories of the anterior cerebral arteries ( aca ) and the left middle cerebral artery ( mca ) .
mr angiography ( mra ) showed the right aca without flow signal , the left internal carotid artery ( ica ) with an intracranial stenosis , and several mca branches with lack of flow ( fig .
several differential diagnoses were considered : dissection , isolated cerebral vasculitis , arterial spasms , infection , multiple cardiac embolism , and intoxication .
screening for heroin , amphetamine , ecstasy , ethanol , and cocaine in blood and urine was negative .
a previously healthy 10-year - old boy was admitted with acute severe left hemiparesis ( nihss 16 ) and headache after jumping on a trampoline .
there was no history of infection or family history of migraine or other cerebrovascular disease .
mri revealed an acute ischemic lesion in the right mca territory , occlusion of the right ica , and a thrombus in the right mca ( fig .
2 ) . intravenous rt - pa infusion ( 0.9 mg / kg ) was started within 3 h after onset of symptoms . as no improvement
was observed at the end of the rt - pa infusion , mechanical revascularization was performed .
a goose neck snare was passed through the thrombus which was partially fragmented and finally dissolved .
flow was established in the right mca and the branches 5 h after the onset of stroke ( fig .
the potential trauma ( bouncing trampoline ) and thrombus formation in the ica made an intima dissection most likely , but could not be confirmed by angiography .
transesophageal echocardiography and routine blood samples , including extensive coagulation tests , were all normal .
the boy improved ( nihss 13 the next day ) and was transferred to the department of pediatric neurorehabilitation on day 3 . at 3 month
, he was back to school , but was still suffering a slight hemiparesis ( modified rankin scale ( mrs ) 2 ) .
the current american heart association pediatric stroke guidelines advocate thrombolytic therapy for childhood ais only in the setting of clinical trials .
in contrast , the european stroke organization guidelines suggest that intravenous rt - pa may be administered in selected patients under the age of 18 beyond the current european recommendations . experience with systemic thrombolytic therapy and intra - arterial revascularization in ais in children is limited . the nationwide inpatient sample in the us recorded data of 2,904 children with stroke .
( 687 children ) , 2% of children received thrombolytic therapy , 9% received intravenous and 6% intra - arterial therapy .
both studies showed increased in - hospital mortality and worse outcome in children treated with thrombolytic therapy compared to conservative treatment , probably reflecting a treatment selection bias towards more severe stroke . furthermore , the thrombolytic therapy often deviated from the current adult stroke guidelines by delayed initiation .
in contrast , a review of 17 cases published in the literature , which were treated with systemic thrombolytic therapy or intra - arterial revascularization ,   probably reflects a publication bias towards positive results with good outcome and low mortality .
our two children were treated according to the stroke treatment guidelines for adults , and no rt - pa related intracranial hemorrhage or other side effects were seen .
lower concentration of tissue plasminogen activator and higher concentration of plasminogen activator inhibitor type 1 in children   might influence the dose - response relation of rt - pa .
systemic thrombolytic therapy is approved in ais in adults , in whom atherothrombosis is the most frequent cause of ischemic stroke .
in contrast , in children , cardiac disease , prothrombotic or hematologic disorders , dissection , moyamoya disease and vasculitis are common etiologies . however , our children were both previously healthy .
in the first case , endovascular therapy was not available in our center at that time .
the history of headache over the last 2 weeks was suspicious for vasculitis , but now signs of inflammation were found and the later organ transplantations caused no systemic vasculitis .
there were no other medical conditions that might have indicated that the changes on mra were associated with the moyamoya syndrome .
another consideration was arterial spasm due to intoxication , but the screening for toxins was negative .
autopsy was not permitted by the parents , and the stroke etiology remained unclear . in the second case ,
the history of a potential trauma and thrombus formation in the distal ica made an intima dissection most likely , but could not be confirmed on angiography or mri after successful mechanical revascularization .
the clinical outcome after 3 month was good ( mrs 2 ) and full recovery was seen after 5 month . in conclusion ,
treatment of ais in childhood without being part of a randomized controlled trial needs a careful individual approach .
differences in the fibrinolytic system and the different etiology of ais in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy .
acute multimodal imaging with mra , ct angiography , or angiography to clarify the etiology of ais might help to select the most appropriate treatment modality .

Answer:
thrombolytic therapy is not recommended for acute ischemic stroke ( ais ) in patients under the age of 18 and published experience is limited . in this case report , we describe two children treated with systemic thrombolytic therapy .
 one child received additional mechanical revascularization and achieved a good clinical outcome .
 the differences in the fibrinolytic system and the different etiology of ais in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy .
 acute multimodal imaging to clarify the etiology of ais might help to select the most appropriate treatment modality .


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:
successful outcomes of endodontic treatment depend on the identification of all roots and root canals which in turn guarantees complete extirpation of pulp tissue , proper chemomechanical cleaning and shaping and three - dimensional obturation of the root canal system with an inert filling material .
failure of at least one of these stages entails high risk of unsuccessful root canal treatment of the tooth with a subsequent development or persistence of a periapical lesion . normally , mandibular first molars have one mesial root and one distally .
the mesial root has two canals ( mesiobuccal and mesiolingual ) , ending mainly in two distinct apical foramina .
the distal root typically has one root canal , although if the orifice is particularly narrow and round , a second distal canal may be present .
anatomical variations in the number of roots as well as canal configuration in mandibular molars are not uncommon [ 3 , 4 ] .
one of the major anatomical variations is the presence of an additional third root , also called the radix entomolaris ( re ) which is located distolingually in mandibular molars . in very rare cases , when this additional root is located mesiobuccally , it is called radix paramolaris [ 5 , 6 ] .
anatomical studies have reported an association between the presence of a separate re in the first mandibular molar and certain ethnic groups . in populations with mongoloid traits , such as chinese , eskimos , and american - indians ,
it occurs with a frequency of 5 to more than 30% [ 7 , 8 ] . in african population ,
a maximum frequency of 3% was found [ 9 , 10 ] , whereas in europeans the incidence was even less .
using full - mouth periapical radiographs , investigated the incidence of radix entomolaris in german population .
seven patients were found to have a three - rooted mandibular first molar with an overall incidence of 1.35% . in indian population , garg et al . examined 1054 periapical radiographs and reported 5.97% of occurrence of re in mandibular first molars .
the same method was used by karale et al .   who reported a higher incidence ( 6.67% ) of re .
knowledge of occurrence , location , and incidence of any tooth anatomical variation is important as it has a significant role in clinical dentistry .
many epidemiological studies have highlighted the importance of watching re while performing root canal treatment on mandibular first molars .
dental schools have been very recently established in palestine and there is no single research dealing with teeth anatomy and the incidence of anatomical variation in our country . with a huge number of dentists and very few specialists in endodontics ,
this research has been conducted so as to provide information about various anatomical variations that could be encountered during endodontic therapy .
the purpose of this study was to evaluate the percentage of permanent mandibular first molar teeth with three roots in a palestinian population using conventional digital x - rays in two different angles .
three hundred and twenty two mandibular first molars from 185 females and 137 males of different ages scheduled for root canal treatment at the dental center of the arab american university were included in this clinical investigation .
the study sample represents all patients who needed primary root canal treatment or referred for retreatment over a 2-year period .
the age of the 322 participants ranged from 11 to 62 ( mean = 37 ) years .
this study was approved by the  ethics committee  of the school of dentistry research centre .
the criteria used to indicate the presence of re were clear distinction of an extra root , indicated by the crossing of translucent lines defining the pulp space and periodontal ligaments , originating in the upper half of the distal root .
one endodontist and one paediatric dentist ( both instructors of undergraduate dental students ) served as examiners in this study .
disagreement in the interpretation of the radiographs was discussed between the two investigators until a consensus was reached .
at least two preoperative radiographs were taken for each tooth undergoing root canal treatment using a digital x - ray sensor ( dr . suni , san jose , california , usa ) .
one radiograph was taken from orthoradial position and the other taken either 30 mesially or distally . when the radiographs revealed a case of re , another radiograph for the opposing side was taken .
after obtaining adequate anaesthesia , the tooth was isolated with rubber dam and root canal treatment was initiated .
the pulp chamber was irrigated with 3% sodium hypochlorite and carefully examined with an endodontic probe ( dg-16 , dentsply , gloucester , uk ) .
all canals were scouted using k - file number 10 ( dentsply , maillefer , ballaigues , switzerland ) .
working length was estimated using an apex locator ( novapex , forum technologies , rishon le - zion , israel ) and confirmed with a working length radiograph with k - files introduced into the canals .
ah plus ( dentsply detrey , konstanz , germany ) was used as a sealer .
a postoperative radiograph was taken to assess the technical quality of root canal filling . when satisfactory , a permanent filling was placed .
figures 1 , 2 , and 3 show an example of a mandibular first molar with three roots . the incidence of re and comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded .
comparison of the incidence and the correlations between males and females and left- and right - side occurrences were analyzed by using the pearson chi - square test with spss ( 15.0 ; spss inc . ,
three hundred and twenty two patients comprising 185 females and 137 males formed the study sample .
there was no significant difference in the incidence of three - rooted mandibular first molars between females ( 7/185 ) and males ( 5/137 ) ( table 1 ) .
however , there was a significant difference between the right side ( 8/12 ) and the left side ( 4/12 ) ( p < 0.05 ) .
knowledge of both normal and abnormal anatomy of teeth dictates the parameters for execution of root canal therapy and can directly affect the probability of success .
therefore , practitioners should be familiar with the existence as well as the prevalence of teeth abnormalities .
mandibular first molars seem to be the most frequent teeth in need of root canal treatment as they are the first permanent teeth to erupt . nonetheless , anatomical variations of the root canal system in molars are not appreciated by a great number of general practitioners .
the presence of a third root ( re ) may complicate the endodontic treatment and lead to failure as a result of canal missing .
while conducting root canal treatment in mandibular first molars , clinicians should be aware of this morphological abnormality . de moor et al .
type ii refers to an initially curved entrance which continues as a straight root / root canal .
type iii refers to an initial curve in the coronal third of the root canal and a second curve beginning in the middle and continuing to the apical third .
the infrequent occurrence of re requires that the clinician be cautious in diagnosis and management of the lower molar teeth .
although it is not necessary , an additional root is often associated with an increased number of cusps and an increased number of root canals with a more prominent occlusodistal or distolingual lobe .
radiographs taken at different angulations reveal the basic information regarding the anatomy of a tooth and can thus help to detect any aberrant anatomy such as extra canals and/or roots .
when the outline of the distal root or the root canal seems unclear on the preoperative radiograph , the presence of a  hidden  third root should be suspected .
studies have shown that a second radiograph should be taken from a more mesial or distal angle ( 30 degrees ) which could probably reveal the presence of re .
periapical radiographs were used in this study because they are routinely used in the dental school of the arab american university throughout endodontic steps .
this technique is noninvasive and inexpensive and allows for interstudy comparisons relating to gender and bilateral occurrence difference for three - rooted mandibular first molars . on the other hand , this method has some disadvantages .
as radix entomolaris is mostly situated in the same buccolingual plane as the distobuccal root , a superimposition of both roots can appear on the radiograph resulting in an inaccurate diagnosis .
the digital system offers many advantages over the conventional radiography such as ease and speed of use , reduction in time between exposure and image interpretation , less radiation dosage to the patient , elimination of chemical waste hazard , and the ability to digitally manipulate the captured image .
unfortunately , a more advanced technology represented by the cone beam computed tomography ( cbct ) is not available .
cone beam computed tomography scans were recently shown to be a valuable tool in several stages of endodontic treatment as they provide an immediate and accurate three - dimensional radiographic image .
preoperatively , these images give information about the internal and external tooth anatomy which include number and location of roots and canals , root and canal curvatures , size of the pulp chamber , and the degree of calcification .
cbct images allow a complete elimination of the superimposition of structural images outside the area of interest and provide a high - contrast resolution and data from a single computed tomography imaging process .
they also provide three dimensional images in the axial , coronal , or sagittal planes . in cases of re
, cbct shows the exact position of distolingual root and hence it helps in tracking the curvature and prevents iatrogenic event that might occur in relation to canal curvature like instrument separation , perforation , ledge formation , and so forth .
when the occurrence of re is confirmed or suspected on the radiograph , the access cavity preparation should be modified from the classic triangular access to a more rectangular or trapezoidal outline .
the orifice of re is mainly located disto- to mesiolingually from the main distal canal .
if the entrance of re canal is not clearly visible after removal of the pulp chamber roof , a more thorough inspection of the pulp chamber floor and wall , especially in the distolingual region , is necessary .
the introduction of dental operating microscope ( dom ) has changed the face of endodontics . although the operating microscope is not used in our clinics , its use is recommended in routine endodontic practice as it offers an excellent illumination and magnification of the operating field and provides a tremendous advantage in locating and treating  extra  canals .
coelho de carvalho and zuolo   reported that the dom had enabled them to locate 8% more canals in mandibular molars .
al - nazhan has examined 251 mandibular first molars of saudi patients ( clinically and radiographically ) .
he reported an incidence of 6% of re amongst saudi population . in their clinical investigation conducted on chinese population , yu et al .
screened 378 cases of mandibular first molars with root canal therapy and reported an incidence of 27% of teeth with re . in our study
, the overall incidence of patients with three - rooted mandibular first molars was 3.73% .
this finding was in a range of previous reports on middle easterners [ 24 , 26 ] .
however , it was low when compared with data reported for asian races : 24.5% in koreans , 32% in chinese , and 25.6% in taiwanese . in the present study ,
the same result was reported by other studies [ 11 , 12 , 28 , 30 ] . when considering the right and left sides of the mandible
, three - rooted mandibular first molars occurred more frequently on the right side than on the left side .
these findings were in accordance with some previous studies [ 12 , 28 ] and different from some others [ 11 , 31 ] which reported that re can occur more on the left side .
loh   report a bilateral occurrence of three rooted mandibular permanent first molars from 50 to 67% ; however , in our study the bilateral occurrence was only 33.3% .
this percentage was higher than the study on german population   and much lower than the studies [ 2729 ] involving asian subjects ( koreans , chinese , and taiwanese , resp . ) .
general practitioners as well as specialists in endodontics should always think about a possible third root ( re ) when planning a root canal treatment for a mandibular first molar .
careful clinical and radiographic examination is indispensable in the diagnosis of any anatomic variation in the root canal system of any tooth prior to initiating treatment .
as this study revealed that the incidence of a third root in palestinian population was within the range of previous reports from the middle east but considerably lower than the percentage from the far east , the use of conventional two - dimensional radiographs for the assessment of re would be probably considered as a limitation in the clinical approach and methodology of this study .
hopefully , future research in palestine would be able to study a larger and more varied population utilizing cone beam computed tomography .

Answer:
purpose .
 the aim of this investigation was to evaluate clinically the percentage of permanent mandibular first molar teeth with three roots amongst palestinian population .
 patients and methods .
 three hundred twenty - two mandibular first molars from 185 females and 137 males scheduled for root canal treatment at the dental center of the arab american university were examined over a 2-year period .
 the incidence of a third root revealed by periapical radiographs and the comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded . statistical analysis .
 it was performed using the chi - square test with a significant level set at p < 0.05% .
 results . of the
 322 treated mandibular first molars , twelve teeth were found to have a third root with an overall incidence being 3.73% .
 more teeth with a third root were treated on the right side of the mandible compared to the left side . conclusion .
 the incidence of a third root in palestinian population was within the range of previous reports from the middle east but considerably lower than the percentage from the far east .


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:
positron emission tomography - computed tomography is useful for diagnosing primary and metastatic lesions of esophageal cancer .
the sensitivity and specificity of a pet / ct are also relatively preferable to other diagnostic imaging tools .
although the number of cases is few , false positives exist in which an inflammatory tumor mass and a nonspecific tumor mass are difficult to differentiate between , even when combined with other image findings . in cases of esophageal cancer ,
the types of treatment and their prognosis are greatly affected if there is a metastasis or recurrence .
positron emission tomography - computed tomographic false positives can not simply be ignored even if they appear to be due to inflammation or some other factors .
this case report discusses the reasons to conduct a pet / ct test and its limitations in diagnosing esophageal cancer .
the subjects of this investigation had suspected metastasis from a pet / ct which occurred before surgery of the 129 resected cases of esophageal cancer at our department from june 2010 to march 2015 .
however , after surgery , biopsy and/or follow - up observation , only the cases that were confirmed as metastasis negative were considered to be pet / ct false positives for this assessment .
there were 3 cases of preoperative pet / ct false positives ( table 1 ) .
two cases in which bone metastasis was suspected revealed almost normal range of squamous cell carcinoma ( scc)associated antigen , alkaline phosphatase , and serum calcium levels .
abbreviations : ln , lymph node ; m , metastasis ; mt , middle thoracic lesion of esophagus ; n , node ; t , tumor ; ut , upper thoracic lesion of esophagus . in case 1 , a 59-year - old man , without particular medical history , had a diagnosis of esophageal carcinoma by endoscopy .
multiple bone metastases were suspected by a pet / ct in the spine , sternum , ribs , and pelvic bone ( figure 1 ) . after conducting a ct - guided biopsy of the right iliac bone ,
the patient is alive with no recurrence 4  years and 10  months after surgery , although the false - positive lesions in pelvic bone are still detected by pet / ct . in the case 1
, multiple bone metastases were suspected by a positron emission tomography - computed tomography in the pelvic bone ( suvmax  =  2.94 ) . in case 2 , a 71  year - old man , without particular medical history ,
abnormal accumulations of fluorodeoxyglucose ( fdg ) in the manubrium sterni , vertebra th5 , and the pedicle of vertebral arch were found by pet / ct .
therefore , after the sufficient informed consent , the patient underwent a laryngopharyngeal esophagectomy , a transhiatal esophagectomy without thoracotomy , and reconstruction with the gastric tube through the posterior mediastinal route .
pathological finding showed poorly differentiated scc of esophagus and moderately differentiated scc of hypopharynx with a cervical lymph node metastasis .
the patient is alive with no recurrence 3  years and 11  months after the surgery . in case 3 ,
a 76-year - old man , without particular medical history , had a diagnosis of a superficial esophageal cancer by endoscopy .
he was suspected of lymph node metastasis of right recurrent nerve lymph node ( figure 2 ) by preoperative pet / ct .
. scattered silicotic nodules and inflammatory lymphadenopathy might be caused by pneumoconiosis ( figure 3 ) .
case 3 was suspected of right recurrent nerve lymph node metastasis by preoperative positron emission tomography - computed tomography ( suvmax  =  3.00 ) .
pathological finding of case 3 revealed scattered silicotic nodules in resected lymph nodes with infiltration of histiocytosis to sinusoid .
in esophageal cancer treatment , fdg - pet / ct is also used to diagnose metastases and to judge the effectiveness of treatment . especially , pretherapeutic
there are cases when the surgery may not apply to a patient if remote metastasis or high - grade lymph node metastasis is found .
many cases have already been reported claiming that fdg - pet is a useful modality for a pretherapeutic staging .
esophageal cancer causes 30% to 40% of lymph node metastases among cancers that spread to the submucosa , and the prognosis of esophageal cancer is known to be defined by the presence of lymph node metastasis , how many metastases are present , and how much the metastasis spreads .
therefore , evaluating lymph node metastasis is a very important factor in deciding the course of treatment .
the diagnosability of lymph node metastasis using a fdg - pet for esophageal cancer is generally reported to have a sensitivity of 32% to 51.9% , a specificity of 94.2% to 100% , and an accuracy of 48% to 93% .
in addition , fdg - pet / ct , which is a combination of a fdg - pet and a ct , improves the diagnosability even more .
yuan et al have reported that they evaluated the diagnosability of lymph node metastasis using fdg - pet / ct for esophageal squamous cancer and found a sensitivity of 94% , a specificity of 92% , and an accuracy of 92% . however , the size of a lymph node that can be detected by pet / ct is said to be only 6 to 8  mm , thus it is difficult to detect micrometastasis .
also , detecting metastasis to neighboring lymph nodes could be difficult in cases with a lot of fdg accumulation in the primary lesion , or accumulation in the intestinal tract such as in the stomach , or in the heart .
the fdg accumulates in inflamed lymph nodes as well , so false positives often appear in hilar lymph nodes or in patients who have chronic lung disease .
lymph node metastasis was suspected after a preoperative pet / ct for the case 3 , as described above , but it was actually an inflammatory lymphadenopathy caused by pneumoconiosis .
dual - time - point fdg - pet has been reported to be useful in reducing this kind of false positive .
it uses the time differences of peak fdg accumulation for inflammation versus for tumors . after injecting the fdg ,
pet has revealed occult distant metastases at nodal and non - nodal sites in 5% to 40% of patients .
distant metastases of esophageal squamous cancer are mainly found in the lungs , liver , and bones .
kato et al reported the diagnosability of fdg - pet for esophageal cancer as having a sensitivity of 92% , a specificity of 94% , and an accuracy of 93% . when comparing those numbers to bone scintigraphy , whose diagnosabilities are 77% , 84% , and 82% , respectively , the diagnosability of fdg - pet is superior , especially for osteolytic lesions .
but 2 false positives out of 44 cases came from pet , showing that fdg - pet is not perfect .
the suvmax of metastic tumor might be helpful to increase the accuracy of pet / ct .
our previous study demonstrated that the suvmax of the primary tumor was positively correlated with tumor size and vessel invasion and was positively related to the suvmax of metastic tumor . in the report , the diagnostic accuracy of pet / ct ( 87.3% ) was higher than that of conventional ct scans . when diagnosing metastatic bone tumors , the positive predictive value of bone metastasis is known to be quite high if the findings for both pet and ct match .
therefore , even when bone metastasis is suspected due to abnormal fdg accumulation after a fdg - pet , yet no bone destruction image is found in the same site by ct , then interventional radiology or a surgical biopsy should be conducted to obtain a pathological diagnosis .
this case report was on 3 patients with suspected metastasis due to a false - positive pet / ct who were later confirmed to not have metastasis .
the metastases were originally suspected after conducting a pet / ct before surgery to treat esophageal cancer or during the postoperative course .
conducting a pet / ct is useful when diagnosing esophageal cancer metastasis , but there should be an awareness of the possibility of false positives .
therapeutic decisions should be made based on appropriate and accurate diagnoses , and a pathological diagnosis should be actively introduced if necessary .

Answer:
of 129 esophagectomies at our institute from june 2010 to march 2015 , we experienced three preoperative positron emission tomography - computed tomographic ( pet / ct ) false positives .
 bone metastasis was originally suspected in 2 cases , but they were later found to be bone metastasis negative after a preoperative bone biopsy and clinical course observation .
 the other cases suspected of mediastinal lymph node metastasis were diagnosed as inflammatory lymphadenopathy by a pathological examination of the removed lymph nodes .
 conducting a pet / ct is useful when diagnosing esophageal cancer metastasis , but we need to be aware of the possibility of false positives .
 therapeutic decisions should be made based on appropriate and accurate diagnoses , with pathological diagnosis actively introduced if necessary .


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 success of valproic acid ( vpa , 2-propylpentanoic acid ) , a short branched chain fatty acid , for the therapy of absence seizures , partial seizures , tonic - clonic seizures , bipolar disorder , schizoaffective disorder , social phobias , neuropathic pain and for the prophylaxis and treatment of migraine headaches has spurred investigation for its use in the treatment of other conditions .
treatments for encephalopathy secondary to hyperammonemia as a side - effect of vpa treatment remain empirical and restoration of possible hepatic carnitine deficiency remains controversial .
while some authors have found a positive correlation between plasma ammonia level and vpa dose or concentration others have found none .
her elevated vpa levels were associated with elevated ammonia levels as expected of a positive correlation .
in contrast , later on in the patient 's clinical course her raised venous ammonia levels were found to be slowly down - trending in the presence of sub - therapeutic serum vpa .
the present case report is about a 25-year - old hispanic female with a history of depression since age of 12 years , bipolar disorder , borderline personality disorder , purging type bulimia and history of suicide attempts at age 12 was admitted to the intensive care unit after attempted suicide by consuming an unknown number of vpa pills .
this patient had recently started taking vpa ( depakote ) as a mood stabilizer at a dose of 250 mg at bed time about 3 days earlier , after a failed therapy .
patient was taking paroxetine 20 mg for depression ; this was incremented to 40 mg at the time vpa was started .
she reported that the change to vpa made her listless ,  lowered  her mood , decreased her motivation , worsened her depression and caused suicidal thoughts .
she overdoses herself on vpa which she took with alcohol . after ingesting the pills she notified her family who then brought her to the emergency room . on admission ,
her vitals were stable ( blood pressure : 118/72 mm hg ; temperature : 98.7f ; pulse : 82 beats / min ; oxygen saturation : 99% on room air ) . on initial examination
she looked disheveled , although drowsy , was oriented to person , place and time .
the complete blood count and comprehensive metabolic panel that was recorded initially and subsequently were unremarkable [ table 1 ] .
subsequently , she was administered oral lactulose once and then 1400 mg of levocarnitine orally every 6 h for the next 2 days . her vpa levels which peaked after admission continued to trend down over the next 4 days
, the ammonia levels also peaked subsequent to admission then showed an initial dip followed by a very slow down - trend [ figure 1a ] .
the normalized log - linear plot of vpa serum concentration over time showed a down - trending linear first - order kinetics with a calculated t = 15.08 h [ figure 1b ] ( expected t for depakote : 9 - 16 h following oral dosing regimens of 250 - 1000 mg . the serum ammonia normalized log - linear plot in contrast showed two different decay kinetics : initial sharp down - trend for vpa levels greater than 90.9 g / ml but much slower downtrend for vpa levels less than 90.9 g / ml down into the subtherapeutic range of 8.5 g / ml .
patient continued to complain of lethargy for the next 4 days which subsequently alleviated . at 14 days
laboratory values of the patient at the time of admission ( a ) valproic acid ( vpa ) and ammonia levels as a function of time ( days ) .
vertical axes : straight line ( left ) : vpa levels ; dashed line ( right ) : venous ammonia levels .
( b ) logarithm of normalized vpa and ammonia levels as a function of time in days .
the normalization for each compound , for levels at each recorded time point ( x ) was to its recorded maximum level ( xmax ) .
the normalized log - linear plot of vpa showed linear first - order decay kinetics with a calculated t = 15.08 h ( r = 0.994 )
recognition of symptoms of hyperammonemia remains a challenge especially in psychiatric patients . in a review of 11 case reports of symptomatic hyperammonemia in a psychiatric setting it was noted that acute hyperammonemic encephalopathy in psychiatric patients may present in various ways , sometimes with subtle clinical features .
the previously reported spectrum of clinical features included : improvement in mood , worsening of psychiatric symptoms , mild complaints of fatigue and delirium . in our patient ,
hyperammonemia secondary to vpa overdose caused listlessness ,  lowering  of mood , decreased motivation , worsening depression and suicidal ideation .
we observed presence of vpa in serum caused increased venous ammonia levels , which eventually trended down to normal after its cessation .
increasing vpa levels in serum was associated with increasing venous ammonia levels initially [ figure 1 ] .
the peak concentration of ammonia noted was likely a decrement from the real peak based on the time to peak of depakote tablets being 4 h ( the patients initial vpa levels were measured at 2 h after she allegedly consumed the vpa while the next blood draw was 9 h later ) .
we also made the following observations : ( 1 ) raised venous ammonia levels may remain symptomatic for a significant period of time beyond discontinuation of vpa .
( 2 ) existence of more than one concurrent mechanism with different decay kinetics in the metabolism of ammonia in presence of high or low concentrations of serum vpa .
unmasking of an inherent urea cycle metabolic disorder could have amplified the differential decay rates of venous ammonia .
the possibility of more than one mechanism causing hyperammonia secondary to vpa use is suggested by the different proposed mechanisms of vpa metabolites causing hyperammonemia , these include : ( 1 ) propionic acid inhibiting the urea cycle enzyme carbamoyl phosphate synthetase i ; ( 2 ) valproyl - coa or a closely related compound as a proximate inhibitor of mitochondrial ureagenesis ; ( 3 ) valproyl - carnitine ester causing a relative carnitine deficiency and ( 4 ) 2,4-dien - vpa inhibiting b - oxidation .
although , we can not speculate on the mechanisms responsible for the different kinetics of decay of ammonia levels in the presence of down - trending vpa levels we can confidently state that non - elevated hepatic enzymes and hyperammonemia despite carnitine replacement indicated that hepatic damage and carnitine deficiency had very little role in causing the slowly down - trending elevated ammonia levels in the presence of subtherapeutic serum vpa levels .
hyperammonemia and psychiatric disturbance secondary to valproate use in our case showed a score of 9 by a naranjo algorithm , indicating strong causality with the drug and placing it in causality category of  definite .
our assessment of a high adverse reaction probability scale was based on the fact that there are previous conclusive reports of hyperammonemia secondary to vpa use with similar psychiatric features as presented in this case report , hyperammonemia occurred only after vpa use and eventually trended down to normal levels with discontinuation of vpa , patients psychiatric disturbance correlated with hyperammonemia , the patient symptomatically improved with drug discontinuation , there are no alternative explanation of hyperammonemia and altered mood in this case , the serum levels of vpa were elevated with concentrations known to be toxic and that toxic effects observed were more severe with high dose and less severe when secondary hyperammonemia decreased .
this case report suggests that hyperammonemia , which is known to occur in about 50% patients treated with vpa , may have more than one concurrent etiologic mechanism with different decay kinetics which are not related to hepatic damage or carnitine deficiency .

Answer:
valproic acid ( vpa ) has successfully been used in the therapy of a number of conditions including absence seizures , partial seizures , tonic - clonic seizures , bipolar disorder , schizoaffective disorder , social phobias , neuropathic pain and migraine headaches .
 there is a high rise in number of cases of toxicity due to overdose of vpa .
 hyperammonemia , a common side - effect of vpa , is caused by several proposed etiologies , reported as having uncertain correlation with vpa dose or concentration .
 we present here a case of a 25-year - old female patient with a past history of psychiatric complaints , presented with elevated serum vpa levels associated with elevated venous ammonia levels subsequent to vpa overdose . later in the presence of sub - therapeutic serum vpa levels
 her venous ammonia levels remained raised and slowly down - trending .
 vpa levels and ammonia levels were found to be normal after 14 days .
 patient was treated with levocarnitine .
 her liver enzymes were never elevated .
 different decay kinetics of venous ammonia in presence of high and low concentrations of vpa indicates that vpa can cause symptomatic hyperammonemia via more than one concurrent etiological mechanism . in this patient ,
 the mechanisms causing hyperammonia secondary to vpa use were not related to hepatic damage or carnitine deficiency .


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:
topical steroid - dependent face is a common condition resulting from misuse of topical steroids over the face which may lead to erythema , burning and scaling .
. the common indications are conditions such as psoriasis , lichen planus , eczema , lichen simplex chronicus , and other steroid - responsive dermatoses . however , because of their property of producing bleaching and anti - inflammatory effect , they have been misused frequently .
they are misused for varied indications such as acne , pigmentation , fungal infection , pruritus , and many a times as a cosmetic or a skin cream for any type of rash .
the main reason for such misuse in our country is its free availability as an over - the - counter ( otc ) medication .
furthermore , topical steroids are available in various irrational combinations which cause more damage to the skin . there are studies which have tried to highlight the various side effects and harm caused by misuse of topical steroids and its combinations .
these studies have tried to bring to the notice of regulatory authorities about the damage caused by the free availability of these creams . in this study , we have tried to find out the awareness among patients about these drugs and also as to how many of them have used these medicines .
this was a prospective study conducted at the dermatology outpatient department ( opd ) in a tertiary care hospital .
a total of 1000 adult patients attending the dermatology opd were included in the study . each patient attending the dermatology opd irrespective of their complaints
the questions mainly tried to find out if the patients had ever heard about the commonly abused topical steroids and its combinations ( betnovate , skinlite , melacare , panderm , fourderm , lobate gm , quadriderm ) in our area and if they had used any of those creams .
they were also asked about usage of any other creams other than the ones mentioned in the list .
furthermore , they were asked regarding who suggested those creams to them , the duration of usage , and if they noticed any side effect .
patients < 18 years and those not willing to answer the questionnaire were excluded from the study .
a total of 1000 adult patients ( male : 360 , female : 640 ) were included in the study .
eight hundred and nine patients out of the 1000 patients had heard about at least one of the topical steroids mentioned in the questionnaire .
six hundred and twelve patients ( 400 female and 212 male ) had used the topical steroid or its combination for various indications [ table 1 ] .
brand names of the topical steroid - containing products the indications for which these medicines were used included acne ( 30.2% ) , allergy ( 14.8% ) , pigmentation ( 11.4% ) , boils ( 0.3% ) , eczema ( 0.98% ) , fairness ( as cosmetic 10.8% ) , fungal infections ( 3.4% ) , injury ( 3.5% ) , itching ( 11.7% ) , oily skin ( 0.65% ) , skin rashes ( 7.1% ) , white patches ( 1.9% ) , and burns ( 0.32% ) .
acne was the most common indication for which topical steroid was used , followed by allergy and rashes . around 66 ( 10.8% ) patients were using these medicines as a cosmetic for fairness and 70 ( 11.4% ) patients were using it to remove pigmentation due to various reasons .
overall 52.4% of patients were using these creams mainly over the face and rest of them were using it over other parts of the body as a general skin cream for any rashes .
friends had suggested these medicines in 191 ( 31.2% ) patients , followed by pharmacists in 71 ( 11.6% ) patients .
the duration of the usage of these creams varied from 1 day to 10 years . around 383 ( 62.5% )
patients had used these creams for a duration varying from 1 week to 3 months .
one hundred and seven ( 17.4% ) patients had used these creams from 3 months to 2 years .
three hundred and eighteen ( 51.9% ) patients complained of some form of side effect after using these creams .
one hundred and twenty - seven patients complained of aggravation of symptoms , 65 patients complained of increased pigmentation [ figure 1 ] , 26 patients developed pimples [ figure 2 ] , and redness and irritation was seen in 74 patients .
other minor side effects included white patches , burning sensation , and no improvement of the skin problem [ table 2 ] .
pigmentation due to use of topical steroid adverse effects as complained by the patients using topical steroids
topical steroids were first used in dermatology by sulzberger and witten in 1952 when they published an article on the effect of topically applied compound f in selected dermatoses .
topical steroids have greatly contributed to the dermatologist 's ability to effectively treat several difficult dermatoses .
they were hailed as a panacea for all ills by physicians and patients and gained rapid popularity .
topical steroids are one of the most commonly used drugs by dermatologists worldwide . however , the dramatic symptomatic relief from these medications led to misuse and abuse of these drugs by both nondermatologists and patients .
the rampant misuse and abuse of these medicines led to the development of various side effects , both cutaneous and systemic .
various studies have tried to highlight the menace caused by the use of topical steroids . a multicentric study by saraswat et al .
has also been done to highlight the topical steroid abuse on the face . around 2296 patients with facial dermatoses
were screened , of which 433 patients were using topical steroids . in our study , we have included 1000 adult patients attending dermatology opd irrespective of their skin complaints .
we have tried to find out how many patients have heard about any of the common topical steroids available otc in our area and also how many of them have used these creams . around 809 patients ( 80.9% ) had heard of at least one of the topical steroids or its combinations .
six hundred and twelve ( 61.2% ) patients had used one of the steroids or steroid combinations for a duration varying from 1 day to 10 years .
the common indications for which steroid was used were acne , fairness ( as cosmetic ) , pigmentation , and allergy .
the findings are similar to the study conducted by saraswat et al . and dey .
an iraqi study showed 7.9% of patients using topical steroid for similar indications . in our study , 302 ( 49.5% ) patients who had used the steroid had received the prescription from a doctor . in the study by saraswat et al .
, 41% of the patients had received the recommendation from a doctor . in the present study , 301 ( 49% )
patients were advised to use these medicines by pharmacists , friends , and relatives . however , most of the time , general practitioners and doctors from alternative medicine had prescribed these medicines .
general practitioners and pharmacists are often the first point of contact for most of the patients .
training and sensitizing them regarding steroid abuse would help in reducing the incidence of topical steroid - related side effects .
the common side effects found in our study were acne , pigmentation , redness , itching , burning sensation , striae , and aggravation of existing skin problem .
these are similar to the findings by saraswat et al . and dey . the nature of side effect correlated with the duration of the usage of topical steroid .
however , many of our patients were not aware of the fact that the problems they were facing were due to the long - term use of steroids .
from the findings of our study and other studies , we would like to conclude that topical steroid abuse is rampant in our population .
the reason for this varies from wrong prescription , dubious marketing by pharmaceutical companies , free availability of these medicines as otc drugs , and lack of regulations regarding the manufacturing of irrational combinations .
as general practitioners and pharmacists are recommending these products in majority of the cases , it is very important to sensitize these people about the possible complications of these drugs and the extent of problem the society is facing because of irrational and unregulated use of these drugs .
our study aims to highlight the misuse of steroids and its combination anywhere on the body .
our study was an outpatient - based study , and further larger studies will give a clearer picture about the magnitude of the steroid abuse .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
topical steroid abuse is not only limited to the face but also over the rest of the body .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
topical steroid abuse is not only limited to the face but also over the rest of the body .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
topical steroid abuse is not only limited to the face but also over the rest of the body .

Answer:
background : topical steroids are one of the most commonly abused drugs .
 there are only a few studies available which have highlighted the severity of this problem in india .
 however , these studies have concentrated mainly on the topical steroid abuse and its side effects over the face.aims:the aim of this study was to know the awareness among the people about various commonly available topical steroids and their combinations irrespective of usage and to know the extent of misuse of these drugs . along with this
 , we also tried to find the source of recommendation of these medicines which will help to sensitize people about this menace.materials and methods : this was a prospective , questionnaire - based study done at a tertiary care hospital .
 a total of 1000 adult patients attending the dermatology outpatient department were administered a questionnaire about awareness and usage of topical steroid and its combinations.results:a total of 1000 adult patients were included in the study , out of which 809 ( 80.9% ) patients had heard about at least one of the topical steroids or its combinations mentioned in the questionnaire .
 six hundred and twelve ( 61.2% ) patients had used these creams .
 acne and pigmentation were the most common indications for which topical steroid was used .
 these medicines were recommended by general practitioners in 302 ( 49.5% ) patients and pharmacists in 71 ( 11.6% ) patients .
 totally , 318 ( 51.9% ) patients complained of some form of side effect after using these creams .
 aggravation of the symptoms and increased pigmentation were the most common adverse effects.conclusion:misuse of topical steroids not just over the face but also as a cream for any skin problem is quite common .
 most of the times , it is recommended by general practitioners or pharmacists .
 it is very important to sensitize these people about the possible complications of these drugs and the extent of problem the society is facing because of irrational and unregulated use of these drugs .


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:
hidradenomas are benign cutaneous tumors of sweat gland origin , with the clear cell type constituting the most frequent histologic variety . usually , they are diagnosed in the elderly population , the peak incidence being the fifth to sixth decade .
we describe a young girl , in whom nodular hidradenoma developed at the age of 6 years .
hence , our case demonstrates that nodular hidradenoma is a rare differential diagnosis of skin tumors , even in the pediatric age group .
a 10-year - old girl presented to us with a swelling on the left thigh , which had been progressively enlarging over the preceding 4 years .
cutaneous examination revealed a solitary erythematous dome - shaped , well - circumscribed tumor , measuring approximately 6 cm  4.5 cm .
there was spontaneous dripping of straw - colored serous fluid at the rate of 2030 drops / min , the discharge accentuating on pressure .
biochemical analysis of the serous fluid revealed glucose 25 mg / dl , protein 4 g / dl , sodium 131 mmol / l , and potassium 4.3 mmol / l , almost similar to that of serum , the low concentration of glucose compelling us to think of something else . the mass was excised .
the solid portion was largely composed of a cell type having finely granular , faintly eosinophilic cytoplasm with a dark - colored round to oval nucleus .
the cyst was lined by a single layer of cuboidal epithelium without evidence of decapitation secretion [ figure 5 ] .
solitary dome - shaped , well - circumscribed tumor over the left thigh photomicrograph showing a well - encapsulated mass composed of solid and cystic portions ( h and e , 40 ) photomicrograph showing a well - encapsulated mass with large cystic spaces within it .
ductal luminal structures can be appreciated ( h and e , 100 ) photomicrograph showing clear cells in the center along with cystic spaces ( h and e , 400 ) note the large cystic cavity within the mass .
clear cell hidradenoma or eccrine acrospiroma of the skin was first described by liu , in 1949 , as clear cell papillary carcinoma of the skin .
it was reported under various designations such as nodular hidradenoma , eccrine acrospiroma , solid - cystic hidradenoma , clear cell acrospiroma , clear cell myoepithelioma , and eccrine sweat gland adenoma .
clinically , nodular hidradenoma presents as a slow - growing , red- , blue- , or brown - colored solitary , 530 mm in size , freely mobile and firm nodule , with an occasional cystic appearance .
these are most commonly found on the scalp , face , thorax , abdomen , and gluteal region .
this tumor is found mainly in adults and is excised more commonly in women than in men .
our patient was a young girl who presented with a gradually increasing swelling on the lower limb , a site that is unusual for the development of nodular hidradenoma .
literature search showed very few cases of nodular hidradenoma on the lower limb , that too in the pediatric age group .
however , a case of nodular hidradenoma masquerading as umbilical polyp has been reported in a 1-year - old male child
our patient complained of serous discharge from the lesion , for the preceding 3 months .
clinical differential diagnoses for our case were cutaneous lymphoma , dermatofibrosarcoma protuberans , epidermoid cyst , and sweat gland tumor . however , histology reliably excluded all the possibilities .
it was predominantly composed of a cell type having finely granular , faintly eosinophilic cytoplasm with a dark - colored round to oval nucleus .
the chronically discharging nature of the tumor in our patient was attributable to the fluid - filled cavity within the lesion .
biochemical analysis of the fluid was almost consistent with that of serum , however , the low concentration of glucose hinted that it might be normal sweat .
recently , nuclear grooving has been described as a useful morphological feature to aid in its diagnosis .
immunohistochemical staining of the tumor cells demonstrates positive staining with antibodies against ck - cam 5.2 , ber - ep4 , p63 , epithelial membrane antigen , s-100 protein , smooth muscle actin , and vimentin .
however , due to unavailability of resources and financial constraints , the immunohistochemical analysis could not be performed in our case .
the high rate of local recurrence ( 10% ) and potential for malignant transformation make surgical removal with wide margins as the widely accepted modality of treatment .
the high recurrence is attributable to incomplete resection and to tumor tissue located between the dermis and subcutaneous tissue .
these are characterized by increased mitotic activity , angiolymphatic invasion , local extension into deeper tissues , and a dispersed pattern of growth .
nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .

nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .
nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .

nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .
nodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .

nodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,
the lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .

Answer:
a 10-year - old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion . based on histological features of the excised tumor , a diagnosis of nodular hidradenoma was made .
 atypical features including large size of the tumor , location on the lower limb , a weeping presentation , and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case .


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:
haemolytic uraemic syndrome ( hus ) is most frequently caused by infection with shiga toxin - producing strains of escherichia coli or shigella dysenteriae type 1 .
other causes include inherited and acquired abnormalities affecting the alternative pathway of complement , other infections and certain drugs , including cisplatin   and carboplatin .
recently eculizumab , a humanized monoclonal antibody directed against c5 that prevents the activation of the terminal complement pathway , has been shown to be an effective treatment for patients with atypical hus ( ahus ) .
thrombotic microangiopathy has long been recognized as a complication of disseminated cancer   and cisplatin therapy .
the acute form has a high mortality rate , although successful treatment with plasma exchange has been described [ 2 , 7 , 8 ] .
a previously well 27-month - old boy with no family history of kidney disease presented with a cervical mass unresponsive to antibiotics . the plasma lactate dehydrogenase ( ldh ) was elevated at 1600 iu / l ( normal 266500 ) .
bone marrow examination and metaiodobenzylguanidine ( mibg ) scan showed no evidence of distant metastases .
pre - treatment , the plasma creatinine concentration was 21 mol / l , and the glomerular filtration rate ( gfr ; measured by plasma disappearance of technetium ( tc)-99 labelled diethylene triamine pentacaetic acid ( dtpa ) was 107 ml / min/1.73 m body surface area .
therapy was started with a combination of vincristine , etoposide , carboplatin , cisplatin and cyclophosphamide . on day 45 of treatment ( 35 days after the first cisplatin dose , 15 days after the second )
, the gfr had fallen to 60 ml / min/1.73 m. this was presumed to be due to acute cisplatin nephrotoxicity .
the hypertension became increasingly severe ( maximum value recorded 160 mmhg systolic ) and he required five agents to control the blood pressure .
he required seven infusions of platelets and four of red blood cells between days 50 and 59 , suggesting that the pancytopaenia was not solely due to myelosuppression and the plasma creatinine concentration rose from 39 to 140 mol / l .
a blood film confirmed the presence of schistocytes , the ldh had risen to 2438 iu / l and the plasma haptoglobin concentration was < 0.06
g / l ) and c4 ( 0.20 g / l ) concentrations were normal .
renal biopsy was considered unsafe at this time , but the results above were considered compatible with a diagnosis of hus , likely due to cisplatin . stool and blood cultures were negative , as were serological tests for hiv1&2 .
adamts13 ( von willebrand factor - cleaving protease ) levels were 80% of control values . despite the dearth of information concerning the pathogenesis of cisplatin / carboplatin - associated chemotherapy , we opted for therapy with eculizumab partly because it was felt that his severe hypertension , profound thrombocytopaenia and small size made plasma exchange hazardous .
he received the first dose of 600 mg the following day when his plasma creatinine was 155
the next day the plasma creatinine peaked at 160 mol / l and it steadily decreased thereafter ( figure  1 ) .
after a further dose of 300 mg a week later , he was maintained on fortnightly doses of 300 mg according to the manufacturer 's dosing guidelines .
five weeks after administration of the first dose of eculizumab , the plasma creatinine concentration had reduced to 34
iu / l and the gfr was 67 ml / min/1.73 m. a decision was made to avoid further exposure to platinum - containing agents , and therapy was changed to a combination of vincristine , topotecan and doxorubicin .
there was little further change in tumour size and , 126 days after starting chemotherapy , the tumour was surgically removed with clear excision margins and eculizumab was discontinued . at this time , the platelet count was 181  10/l and the plasma creatinine concentration was 34
the platelet count fell to 138 four weeks after the last eculizumab dose and remained in the range of 98160  10/l for the next 2 months .
two months after discontinuing the eculizumab , the plasma ldh had risen to 807 iu /
the plasma concentration of the terminal complement complex ( sc5b-9 ) was elevated at 137 ng / ml ( normal range < 80 ) .
of the 20 glomeruli in the light microscopy sections , five were globally sclerosed , and two showed periglomerular fibrosis .
the patent glomeruli showed an increase in mesangial cells and matrix with segmental sclerosis and capsular adhesions .
the toludine blue preparation and electron microscopy ( em ) showed thickened glomerular capillary loops ( double contour appearance ) , and areas of widening of the sub - endothelial space were seen .
this marked widening of the sub - endothelial space and fibrillar / particulate material is characteristic of hus ( figure  2 ) .

light microscopy showing sclerosed glomeruli ( to the left of the figure ) and a glomerulus showing increased mesangial matrix expansion and segmental sclerosis ( boxed area ) .
there is also focal tubular atrophy around damaged glomeruli ( jones silver histochemical stain , scale bar = 10 m ) .
( b ) high power light microscopy showing glomerulus with mesangial matrix expansion and segmental sclerosis ( asterisks ) ( jones silver histochemical stain , scale bar = 5 m .
( c ) toludine blue semithin preparation showing increased mesangial matrix expansion and segmental sclerosis ( asterisks ) and thickened capillary loop ( arrow ) mimicking membranoproliferative glomerulonephritis , scale bar = 5 m .
( d ) em showing fluffy - like material within a markedly widened sub - endothelial space consistent with hus scale bar = 2 m .
light microscopy showing sclerosed glomeruli ( to the left of the figure ) and a glomerulus showing increased mesangial matrix expansion and segmental sclerosis ( boxed area ) .
there is also focal tubular atrophy around damaged glomeruli ( jones silver histochemical stain , scale bar = 10 m ) .
( b ) high power light microscopy showing glomerulus with mesangial matrix expansion and segmental sclerosis ( asterisks ) ( jones silver histochemical stain , scale bar = 5 m .
( c ) toludine blue semithin preparation showing increased mesangial matrix expansion and segmental sclerosis ( asterisks ) and thickened capillary loop ( arrow ) mimicking membranoproliferative glomerulonephritis , scale bar = 5 m .
( d ) em showing fluffy - like material within a markedly widened sub - endothelial space consistent with hus scale bar = 2 m .
the haematological , biochemical and histopathological features suggested active hus , and eculizumab was therefore recommenced with an initial dose of 600 mg given 105 days after the last dose . before restarting the eculizumab ,
the gfr was measured at 54 ml / min/1.73 m , the serum complement c3 concentration was 0.9
the total haemolytic complement ( ch50 ) was 111% , but the alternative pathway haemolytic complement ( ap50 ) was low at 34% ( normal 80200 ) .
g / l ) , normal platelets ( 248  10/l ) and a plasma creatinine concentration of 32 mol / l .
the gfr had risen to 71 ml / min/1.73 m. the plasma concentration of sc5b-9 remained elevated at 133 ng / ml , casting doubt on the suitability of this assay for assessing activity and response to treatment .
dna extracted from a buccal smear at the time of diagnosis of hus was amplified by pcr for all coding exons  10 bases of the cfh ( factor h ) , cfi ( factor i ) , c3 ( complement component 3 ) , cfb ( factor b ) and cd46 ( membrane cofactor protein , mcp ) genes .
amplified products were subjected to bi - directional sanger sequencing ( abi ) , as previously described .
cd46 expression on cell surfaces was assessed on peripheral blood neutrophils after recovery from myelosuppression by flow cytometry using cd46 fluorescein isothiocyanate - conjugated antibody ( bd pharmingen , 555949 ) .
an intronic sequence variant ( c.1027 + 5g > t ) was identified in cd46 .
this variant had not been previously reported nor was it detected in dna from 188 normal control subjects . in silico splicing prediction analysis undertaken using alamut ( interactive bioscience software , seine biopolis , 70 route de lyons - la - foret , 76 000 rouen , france ; http://www.interactive-biosoftware.com ) suggests that this variant may cause aberrant splicing .
after discussion with the parents , a decision was made not to test other family members , because the result was felt to be of limited clinical utility , outweighed by potential anxiety induced in a carrier .
endothelial cells , glomerular basement membrane and podocytes all show ultrastructural evidence of damage after cisplatin exposure .
opsonization of damaged or apoptotic cells with c3b plays an important role in the efficient removal of such cells by phagocytes , and there is evidence of complement activation in cisplatin - induced aki . on host cell surfaces ,
deposited c3b is usually rapidly inactivated by several regulatory proteins including cd46 ( mcp ) and factor h , both of which act as cofactors for factor i. deficiency or reduced activity of these complement regulatory proteins would potentially lead to amplification of the endothelial cell damage induced by cisplatin .
ahus is most frequently associated with impaired regulation of the alternate pathway of complement regulation on the surface of host cells with normal regulation in the fluid phase , and plasma c3 levels are therefore frequently normal . because endothelial damage is associated with complement activation   and c5
plays a pivotal role in the development of ahus , it seemed appropriate to initiate treatment with eculizumab .
the finding of a novel mutation causing decreased expression of cd46 suggests that dysregulated complement activation played an important role in pathogenesis . the response to eculizumab , deterioration on withdrawal of eculizumab and improvement after restarting treatment all support this hypothesis .
our patient is the first to have genetic investigation of the factors involved in the regulation of the alternative pathway of complement regulation and the first to be treated with eculizumab .
the possibility that dysregulated complement activation underlies the thrombotic microangiopathy in other patients with cisplatin - induced hus should be considered , and testing for abnormalities of complement regulation should be performed in future patients .
the optimal duration of eculizumab therapy remains unclear ; 4 months of therapy was clearly inadequate in our patient but we hope to be able to withdraw treatment in the future .
r.d.g . received a travel grant to attend the era - edta conference in paris in 2012 .

Answer:
a 2-year - old patient with a neuroblastoma developed haemolytic uraemic syndrome ( hus ) following treatment with cisplatin and carboplatin . following treatment with eculizumab
 , there was a substantial improvement in renal function with the recovery of the platelet count and the cessation of haemolysis .
 subsequent investigations showed a novel , heterozygous cd46 splice site mutation with reduced peripheral blood neutrophil cd46 expression .
 withdrawal of eculizumab was followed by the recurrence of disease activity , which resolved with re - introduction of therapy .
 abnormal regulation of complement may be associated with other cases of cisplatin - induced hus and treatment with eculizumab may be appropriate for other affected individuals .