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:
recurrent epithelial ovarian carcinoma has a poor prognosis and is almost always fatal [ 1 , 2 ] .
the most frequent relapse site involves the peritoneal cavity and the infradiaphragmatic lymph nodes . outside the abdomen ,
the most frequent metastatic sites are the pleura and the mediastinal lymph nodes [ 3 , 4 ] .
although nodal metastases are well known in the course of epithelial ovarian carcinoma , solitary lymph node relapses are rarely described . the cervical , supraclavicular , groin and axillary areas are unusual sites of isolated lymph node involvement . in a retrospective study evaluating 640 ovarian cancer patients ,
prognosis of isolated lymph node relapse seems better than that of metastatic recurrence at other sites and in the event of an asymptomatic relapse , immediate or delayed therapy should be assessed .
recurrence of ovarian carcinoma is commonly suspected when there is a progressive increase of the serum ca-125 level , but it does not allow differentiation between localized and diffuse tumor spread .
ct scan is the imaging technique of choice , but its capability to detect residual tumor is limited in case of small metastases , such as peritoneal , mesenteric and omental recurrences .
f - fdg - pet can detect residual tumor with a higher accuracy than ct and even with a higher sensitivity than the tumor markers ca-125 [ 7 , 8 ] .
recently , we have observed internal mammary lymph node metastases diagnosed by f - fdg - pet / ct as a solitary recurrence site in 3 ovarian cancer patients .
a 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .
a pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .
1a , b ) , with suspected infiltration of the right side of the sternum ( fig .
a ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .
she was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,
the serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .
external radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .
pet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .
6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007
, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008
, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .
she was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,
disease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .
a 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .
subsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments
, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable . in absence of other signs of localizations ,
the patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .
radiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .
she was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .
no postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .
she was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,
almost 5 years later , the patient was well and showed no evidence of disease .
a 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,
6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .
thus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .
from april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .
the serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .
a 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .
a pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .
1a , b ) , with suspected infiltration of the right side of the sternum ( fig .
a ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .
she was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,
the serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .
external radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .
pet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .
6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007
, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008
, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .
she was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,
disease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .
a 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .
subsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments
, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable .
in absence of other signs of localizations , she was treated with gemcitabine + vinorelbine over a 4-month period .
the patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .
radiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .
she was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .
no postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .
she was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,
almost 5 years later , the patient was well and showed no evidence of disease .
a 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,
6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .
thus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .
from april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .
the serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .
we have been unsuccessful in finding reports on internal mammary lymph nodes metastases from ovarian cancer in the recent literature . in this case report , we have presented 3 cases of recurrent ovarian cancer in which pet / ct detected internal mammary lymph node metastases as unique site of disease , 6 , 9 and 11 years after the primary surgical operation , respectively . in the first and third case ,
pet / ct confirmed the recurrence suspected by the increase of the serum ca-125 level ; in the second case , pet / ct was carried out as a follow - up examination in absence of symptoms or increased serum ca-125 levels . in these 3 patients ,
the pet / ct scan has enabled a local therapeutic approach : a surgical treatment in two patients and radiation therapy in 1 patient , permitting a local control of the disease . at , respectively , 4.5 , 8 and 2 years after the diagnosis of internal mammary lymph node metastases our patients are still alive .
to our knowledge , this is the first report on internal mammary lymph nodes as a site of late and very late solitary ovarian cancer recurrence and on the determining role of pet / ct scan for the diagnosis of isolated tumor involvement and therapeutic decisionmaking . surgical dissection or radical radiotherapy

Answer:
internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described . in this case report ,
 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented .
 18f - fdg - pet / ct allowed the diagnosis which was suspected by the increase of the serum ca-125 level in 2 out of 3 cases .
 local treatment , consisting of surgery ( in 2 patients ) and radiation therapy ( in 1 patient ) , permitted an optimal long - term disease control .


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:
along with the introduction of effective therapeutic agents such as somatostatin analogue ( ssa ) , multityrosine kinase inhibitor and mammalian target of rapamycin inhibitor , much improvement has been made in the treatment of neuroendocrine tumors ( net ) .
especially , the promid   and radiant   studies proved the effectiveness of these new therapeutic agents in the treatment of mid gut and pancreatic net , respectively .
however , in the case of metastatic gastric net , there is neither an established treatment strategy nor a prospective study because gastric nets are not only rare but also mostly diagnosed in the early stage , which can be controlled by surgical resection .
therefore , gastric net has been considered a part of the gastroenteropancreatic net category and there have been no studies exclusively aimed at gastric net . in the treatment of metastatic net , a treatment approach according to the presence of hormonal symptom , embryological origin of primary site and pathologic grade is usually accepted as a principle . however , in the case of gastric net , a separate treatment approach depending on a specific classification , which can be recognized based on clinical and histologic characteristics , is considered . in the classification of gastric net , type
i ( 74% of the gastric nets ) is associated with chronic atrophic gastritis and hypergastrinemia , and type ii ( 6% of the gastric nets ) is associated with multiple endocrine neoplasia type i , zollinger - ellison syndrome and hypergastrinemia .
lastly , sporadic type iii gastric neuroendocrine carcinoma ( nec ; 13% of the gastric nets ) is gastrin - independent and carries the worst prognosis . in this paper
, we describe the case of a female gastric net patient with multiple liver metastases who was unresponsive to biologic therapy and cytotoxic chemotherapy .
in addition , we look at the therapeutic strategy for metastatic gastric net together with a literature review .
upper endoscopic examination revealed a localized , fixed and firm subepithelial tumor ( diameter , 2.2 cm ) in the peripyloric area , but there was no evidence of gastric ulcer in the entire stomach ( fig .
a stomach computed tomography ( ct ) was performed and revealed two non - enhancing , low - attenuated liver masses in s4 ( 2.2 cm ) and s5 ( 1.6 cm ) suggesting metastasis ( fig .
laparoscopic antrectomy with gastrojejunostomy and liver biopsy were performed , but hepatic metastatectomy was not tried due to multiplicity .
the biopsy result of both gastric mass and metastatic hepatic nodule revealed a well - differentiated nec ( net g2 by 2010 who classification ) .
pathologically , the tumor was 37  21 mm in size with a negative margin ( distance from resected margin : 0.5 cm ) and infiltrated the muscular propria layer .
microscopically , the tumor cells were medium - sized and uniform in shape and showed moderate cellularity with mild mitosis ( < 1/50 per high - power field ) ( fig .
on immunohistochemical staining , the tumor cells were positive for chromogranin a and cd56a ( fig .
3d ) , and the serum gastrin level was increased to 1,832 pg / ml ( normal range 0108 ) . the vitamin b 12 level was 350 pg / ml ( normal range 211911 ) , chromogranin a level was 356.29 ng / ml ( normal range 2794 ) , 5-hydroxy indole acetic acid level was 3.04 mg / day ( normal range < 10 ) and serotonin ( 5-hydroxytryptamin ) was 48 ng / ml ( normal range < 200 ) .
however , ct and mri did not localize any tumor assumed of gastrinoma . considering the gastrin level and histologic grade
moreover , she complained of abdominal pain with diarrhea and was therefore treated with long - acting repeatable ( lar ) sandostatin at a dose of 20 mg intramuscularly every 28 days .
however , abdominal ct , which was performed 3 months later , revealed progression of the hepatic metastases without tumor recurrence in the operated bed ( fig .
the patient received an etoposide plus cisplatin ( ep ) combination chemotherapy ( etoposide 100 mg / m on days 13 , cisplatin 75 mg / m on day 1 ) . despite 3 cycles of ep chemotherapy , response evaluation identified a stable disease status , and eventually , her disease progressed after 6 cycles of ep chemotherapy ( fig . 2c ) . because of the patient 's economic situation and lack of grounds , targeted agents such as sunitinib and everolimus were infeasible .
therefore , we chose a combination therapy with interferon- ( ifn ) and sandostatin lar . on response evaluation after 3 months of treatment , she showed favorable response with regression of liver metastasis ( fig .
since oberndorfer first denominated the carcinoid tumor in 1907 , there has been much improvement in the classification and treatment of net .
especially the introduction of the new who pathologic classification system , which is based on the ki-67 labeling index and a few landmark studies such as promid and radiant , provided a useful guide to the oncologists dealing with gastroenteropancreatic net . based on these studies
, ssa is known to be effective in the treatment of midgut nets , and cytotoxic chemotherapy such as the ep regimen is known to be effective in the treatment of foregut nets , including pancreatic nets .
however , net can arise in most organs of the body and can show a variety of clinical features according to its origin and the degree of differentiation .
moreover , in the case of nets that originate from rare primary sites , standard treatment strategies have not been defined yet .
although a division according to the embryological origin , which divides nets into foregut , midgut and hindgut nets , has been used in practice , it can not guarantee the homogeneity between the different organs inside the same embryological category .
that is to say , although gastric net embryologically originates from the foregut , we do not know exactly whether it shows an aspect similar to net of the pancreas .
moreover , gastric net has a few distinctive features in its pathogenesis and natural course .
gastric net is known to be derived from the enterochromaffin - like ( ecl ) cells , which produce histamine , express the gastrin receptor and regulate gastric acid secretion .
gastrin , which is released by g cells in the antrum of the stomach , duodenum and the pancreas , stimulate the release of histamine in ecl cells .
therefore , neoplastic changes in ecl cells are often associated with elevated serum gastrin levels . based on this unique pathogenetic background ,
a separate classification system for gastric net was first defined by rindi et al .   in 1993 . according to this classification , gastric net
can be subdivided into types i , ii and iii , depending on the gastrin level and source of hypergastrinemia . a treatment strategy according to that system
because of the relatively benign clinical course , low metastatic potential and low histologic grade of type i and ii gastric nets , the treatment strategy for these types of nets was focused on local control , and the principal treatment was conservative , including endoscopic follow - up or endoscopic mucosal resection . even in the case of multicentric tumor with liver metastasis , antrectomy and the consequent normalization of gastrin levels was considered sufficient for the control of the remnant lesion . as for medical treatment , biologic therapy such as ssa and ifn
a few studies also demonstrated a therapeutic value of octreotide in nets of gastroduodenal origin [ 6 , 7 ] . besides that , khuroo et al
.   showed that long - acting ssa injections reduced serum gastrin and serum chromogranin a levels with a 50% reduction in the visible number of tumors in 3 patients with type i metastatic gastric carcinoids .
ifn- and - have also been used in the treatment of gastrointestinal nets , regardless of functionality .
immune - mediated cytotoxicity , inhibition of progression of the cell cycle from the s to the g2 phase and inhibition of tumor angiogenesis were proposed as main mechanisms of ifn . however , systemic side effects such as flu - like symptoms and hypothyroidism hindered widespread usage as a first - line treatment . according to the european neuroendocrine tumor society ( enets ) guidelines , ssa is known to be valuable for the subgroups of patients with slowly progressive and low proliferative nets ( g1 ) of gastroduodenal origin , and in cases of metastatic g3 necs or well - differentiated but rapidly progressive metastatic disease , combinations of etoposide and cisplatin are recommended .
however , it is not certain whether the histologic grade depending on the rate of cellular proliferation correlates with the classification based on gastrin levels and how to integrate the gastric net and who classifications into the same treatment strategy for gastric nets , especially in cases of metastatic disease .
moreover , there is the opinion that dysplastic cells are less dependent on gastrin stimulation and do not regress in response to reduced circulating gastrin levels .
indeed , a few metastatic cases with a bad prognosis have been reported in type i or ii gastric nets [ 11 , 12 ] . in our case
, the biopsy results showed a well - differentiated , g2 nec with 4% of ki-67 mitosis and an elevated gastrin level of 1,832 pg / ml .
however , there was no evidence of endocrine neoplasia at the other site . based on the histologic grade and gastrin level , type
therefore , we expected good response to ssa , but somatostatin did not achieve response and disease progression was faster than expected .
however , after 6 cycles of ep chemotherapy , the tumor eventually progressed within only 2 months . because the general condition of our patient was infeasible for another cytotoxic chemotherapy , we again used ssa for the relief of functional symptoms and stabilization of the tumor .
in addition , we added ifn- and obtained favorable response . according to previous studies comparing ssa or ifn alone with a combination of the two drugs ,
response was not superior in any of these groups , whereas the side effects leading to an interruption of the therapy were more frequent in the combination group .
however , according to kolby et al . , the combination of ifn- and ssa reduced tumor progression better and for a longer time than either agent alone and was well tolerated because ssa can reduce side effects of ifn- , although the study was aimed at midgut net .
one review article about the combination of ifn- and ssa presented data showing an advantage of additional ifn- after progression following ssa alone .
however , there is not enough statistical evidence for an upfront use of the combination of ifn- and ssa . in summary , for the treatment of metastatic gastric net , both the clinical classification according to the gastrin level and the pathologic grade should be considered .
ssa can be considered a first - line medical treatment for type i and ii metastatic gastric net .
however , the combination of ssa and inf- can be an effective option in cases showing aggressive tumor behavior or after failure of ssa alone .

Answer:
despite remarkable progression in the treatment and classification system of neuroendocrine tumor ( net ) , some questions have remained unanswered .
 the lack of an established treatment strategy for gastric net is one of the problems . because of its paucity , gastric net
 is not discussed in independent , large - scaled prospective studies and tends to be excluded from clinical trials .
 moreover , a separate classification system and some distinguished clinical features render the treatment of gastric net more complicated . here , we present a case of a female gastric net patient with g2 proliferation index and multiple liver metastases .
 based on the histologic grade and a high serum gastrin level , we initially treated her with somatostatin analogue .
 however , the patient did not respond .
 after that , cytotoxic chemotherapy with the etoposide plus cisplatin regimen only showed response in the short - term period .
 however , combination therapy with octreotide and interferon brought about significant regression of the tumor . herein , we present our case together with a literature review of the treatment of metastatic gastric net .


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:
neuromyelitis optica ( nmo ) or devic 's disease is a rare inflammatory , demyelinating disease of the central nervous system ( cns ) that predominantly targets the optic nerves and spinal cord 1 . the disease was first described in 1870 by albutt and 24 years later , devic described the clinical characteristics of nmo
the discovery of a specific nmo immunoglobulin ( nmoigg ) opened a new era in the classification and understanding of the pathogenesis of nmo 3 .
nmoigg binds to aquaporin4 , which is the main channel that regulates water homeostasis in the cns .
diagnostic criteria for nmo with aquaporin4 antibodies ( aqp4ab ) requires at least one core clinical characteristic , a positive test for aqp4ab using best available detection method ( cellbased assay recommended ) and exclusion of alternative diagnoses 1 .
the core clinical characteristics are , for example , optic neuritis , acute myelitis , acute brainstem syndrome , symptomatic narcolepsy , or symptomatic cerebral syndrome with typical nmo brain lesions 1 .
neuromyelitis optica must be distinguished from other demyelinating diseases , for example , multiple sclerosis .
the presence of aqp4ab differentiates nmo from multiple sclerosis ( ms ) with high specificity 4 .
in contrast to typical ms , the clinical events in nmo are usually more severe 5 , 6 .
cerebrospinal fluid ( csf ) findings in nmo are also known to differ significantly from those in classical ms . csfrestricted oligoclonal igg bands are absent in most nmo patients .
however , pleocytosis is usually mild , and frequently includes neutrophils , eosinophils , activated lymphocytes , and/or plasma cells 6 , 7 .
studies carried out in europe , south east and southern asia , the caribbean and cuba suggest that the incidence and prevalence of nmo ranges from 0.050.4 to 0.524.4 per 100,000 , respectively 9 .
the disease is mainly sporadic , although a few familial cases have been reported 10 .
we describe a case of an unusual and severe course of nmo affecting almost the entire spinal cord and brain .
examination on the day of admission revealed normal results as regards ecg , troponin i , and computed tomography ( ct ) of the chest and abdomen .
the next day , the patient reported headache and neurological examination showed rightsided hemiparesis and afferent pupillary defect of the left eye suggesting an afferent optic nerve defect . within a few hours , the patient showed a rapid neurological deterioration with progressive tetraplegia and global decline .
mri of the spinal cord showed myelitis in the spinal cord segments c2 to th5 ( fig .
csf examination revealed polymorphonuclear pleocytosis ( leukocytes 1210  10/l , neutrophils 95% ) and an increased total protein concentration ( 2273 mg / l ) .
due to spinal cord mri and csf findings , infectious transverse myelitis could not be excluded and the patient was treated with dexamethasone , acyclovir , ceftriaxone , ampicillin , and levofloxacin .
( a ) sagittal t2fse mri of the spinal cord showing high signal changes . ( b )
axial t2flair brain mri showing high signal changes in thalami , internal capsule , and corpus callosum .
( c ) axial t2flair brain mri showing high signal changes in pons , medulla oblongata , cerebellum , and middle cerebellar peduncle .
the next day , the patient 's condition worsened ; she became comatose and had a respiratory failure that required assisted ventilation ; this might be caused by bilateral phrenic nerve involvement as its roots originate from c3 to c5 where the lesion was also seen ( fig .
brain mri showed high signal changes in thalami , internal capsule , and corpus callosum ( fig .
1b ) and also similar changes in pons , medulla oblongata , cerebellum , and middle cerebellar peduncle ( fig .
treatment with methylprednisolone and immunoglobulin was attempted and as serum aqp4ab was confirmed as positive ( indirect immunofluorescence assay was used , the titer was 19.85 , normal < 10 ) and the patient did not respond to the treatment , the patient was also treated by means of plasmapheresis .
histological examination of the cns revealed extensive , sharply limited demyelination and axon defect ( fig . 2a and b ) .
the spinal cord was almost entirely affected . only the lumbar area was partly spared .
smaller demyelination foci were found in the periventricular area of the hippocampus and in the corpus callosum .
demyelination was verified by showing both cd68positive macrophage infiltration and betaapp positivity as signs of axonal damage .
( b ) the axon defect is shown by immunostaining ( brown staining ) of betaamyloid precursor protein ( app ) .
this is the first case report of nmo described from finland from the aqp4ab era .
there is only one older publication of a finnish nmo patient from the preaqp4antibody era 11 .
the patient was referred to hospital with an acuteonset chest pain , which is an unusual first symptom of nmo .
demyelination affected almost the entire spinal cord , sparing only partly the lumbar cord , which is unusual at first myelitis .
lesions involving the lumbar or sacral spinal cord in addition to the cervical and thoracic portions have been reported only in 11% of patients at first myelitis .
previous reports have revealed that 92% of the patients have at least one spinal cord lesion extending over three or more vertebral segments at their first myelitis .
it has been reported that seropositive women have more severe clinical attacks than males , as evidenced by high lesion load in the spinal cord and other types of coexisting autoimmunity 6 .
brain mri abnormalities are relatively common and may be relatively unique by virtue of localization and configuration 12 , as seen also in our patient .
the histopathological findings in the cns , csf , and aqp4ab seropositivity are consistent with neuromyelitis opticatype demyelination , although the disease course of our case was not typical of nmo due to its rapid and severe course . according to hospitalbased observational studies , mortality of nmo ranges from 2.9% to 25% and
reported that disease duration at the time of death ranged from 6 months to 23.6 years 6 .
in addition , our patient 's histological examination revealed extensive , sharply limited demyelination of the spinal cord and brain in the acute phase of the disease . to the best of our knowledge ,
the treatment in this particular case was targeted to multiple causes of the symptoms due to the unknown etiology in the beginning of the disease .
acute attacks and relapses of nmo are generally treated with intravenous glucocorticoids followed by plasmapheresis for refractory or progressive symptoms 13 , 14 .
however , there are no controlled trials evaluating the treatment of nmo , and recommendations are primarily supported by data from observational studies and by the clinical experience of experts . despite several forms of treatment , the patient did not survive .

Answer:
key clinical messageneuromyelitis optica is a rare inflammatory , demyelinating disease of the central nervous system that predominantly targets the optic nerves and spinal cord .
 our case represents an unusual and severe course of neuromyelitis optica . despite several forms of treatment
 , our patient died after a severe and shortterm attack .


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

Title:
Direct Amination of \xce\xb1-Hydroxy Amides

Paper sections:

α-Amino amides are very important molecules that are widely used in organic and medicinal chemistry. They are present in many drugs, such as Leukotriene D4, Safinamide, Lidoderm, Altace, Indinavir, Vyvanse, and in all aminopenicillins. They are also present in many natural products, such as canthiumine, coelichelin,[1] zorbamycin,[2] guadinomine B,[3] myrianthine B,[4] abyssenine,[5] paliurine E,[5] and mucronine J.[6] Moreover, α-amino amides are used as building blocks for the synthesis of different molecules and scaffolds like hydantoins.[7] Recently, the use of α-amino amides as organocatalysts for various asymmetric reactions has proven to be an extremely valuable approach owing to their facile structural modification and accessibility.[8]

Tremendous progress has been made in the use of C–N bond formation for direct amination reactions.[9] Recently, more efforts have been focused on the direct amination of alcohols by using transition metals or Lewis acids (Scheme 1, method A).[9–10] These protocols improved the waste balance and are a powerful tool for the C–N bond formation. This approach is also strongly preferred in industry, and more research in this field is desirable.[11]

Despite good progress in this field, the scope of alcohols and amines is largely restricted. Moreover, these approaches are not valid for more complex structure like α-hydroxy amides, and also for inactivated amines, where reaction typically proceeds with poor yield. Direct amination of the α-hydroxy amide is more challenging than the alcohol, as the amide group could hinder the coordination sites on the catalyst to resist direct amination. Therefore, finding a new method for the direct amination of α-hydroxy amide to gain access to highly important α-amino amides remains an important challenge.

Conversely, to the best of our knowledge, there is only one report by Beller and co-workers for the direct amination of α-hydroxy amides (Scheme 1 method B).[12] They used a ruthenium-catalyzed "borrowing-hydrogen" process for the direct amination. This protocol is simple and green, but it involves the use of a costly catalyst and ligands. Moreover, high reaction temperatures and a limited substrate scope were major disadvantages.

Here, we are reporting a TiCl4-assisted, general, economical, base/ligand-free mild method for the direct amination of α-hydroxy amides. The method is distinguishable by its wide scope, which includes primary, secondary and heterocyclic amines, and even indole and a primary amide.

We started our optimization by screening different Lewis acids, as Lewis-acid-activated reactions are well-developed for the direct amination of alcohols, when used in catalytic and stoichiometric amounts.[9–10] We sought to examine the possibility of these economical and non-toxic Lewis acids for the direct amination of α-hydroxy amides. We evaluated different Lewis acids, such as InCl3, ZnCl2, ZrCl4, GdCl2, Sc(OTf)3, TiCl4, and FeCl3, in a catalytic amount at room temperature in 1,2-dichloroethane (DCE); however, a trace of the target product was only observed when using TiCl4. Next, we increased the temperature and catalyst amount of TiCl4. Ultimately, we found that increasing the temperature to 100 °C, and a stoichiometric amount of TiCl4, product formation slightly improved. Then, we screened different solvents with 1 equivalent of TiCl4 at 100 °C (Table 1). In DCE, a low amount of the desired amination product 3a was observed together with a significant amount of starting material (Table 1, entry 1). The reaction did not reach completion even after three days. With further solvent screening, the coupling product yield improved remarkably up to 62% in solvents, such as 1,4-dioxane, toluene, and THF (Table 1, entries 2–4). The reaction in methanol did not proceed at all. In CH2Cl2, a lower product yield (53%) was observed. Further improvement was observed when acetonitrile was used as a solvent, affording the product in excellent yield (85%, Table 1, entry 7). The reaction did not reach completion with xylenes or DMF even after three days.

Aiming to get a higher yield, we turned our attention toward the use of different additives,[9–10] such as bases (KOH and triethylamine) or drying agents (molecular sieves and MgSO4). With these additives, the reaction became slow and did not finish even with longer reaction times, with starting materials remaining unreacted in substantial amounts ≈50–60%. Next, we performed equivalence studies of the amine morpholine and we found that 1 and 2 equivalents of morpholine formed only 23 and 42% product, respectively. When the TiCl4 equivalents were reduced to 20 mol%, no product was formed. However, when using 50 mol% TiCl4, some product was formed (39%), but the reaction remained incomplete even after three days at 130 °C. In conclusion, the optimal conditions for this reaction were 100 °C with 1 equivalent of TiCl4 in MeCN.

With these optimized conditions in hand, we examined the scope and limitations of this TiCl4-mediated amination reaction (Scheme 2). Alkylamines like allylamine, cyclohexylamine, and benzylamine effectively worked, forming the corresponding products in good yields (68, 76, and 83%, respectively).

Arylamines worked well (3e and 3f). Electron-donating and electron-withdrawing substituents on the arylamines were compatible with the reaction, leading to the desired products in good to moderate yield (3g and 3h). Moreover, we expanded the scope of the reaction to heterocyclic amines. Heteroaryl molecules are very important in drugs, as these molecules are present in almost half of the top 200 drugs.[13] Heterocyclic amines like pyrimidine, benzothiazole and benzimidazoles are known to be inactivated amines; however, they can be used in this protocol, providing good yields of 58, 84 and 69%, respectively (3i–3k).

Next, we screened different secondary amines, including cyclic amines like piperidine and thiomorpholine 1,1-dioxide, which also proved to be good substrates. The reaction with indole also provided the product in 36% isolated yield. The low yield owed to incomplete conversion, although the reaction was carried out for three days at 130 °C and up to 3 equivalents of TiCl4. The method also worked for a primary amide, butyramide, to form bis-amide product 3p, in low 15% yield, while recovering mostly starting material (>50%).

Finally, we extended the scope of the reaction to differentially substituted α-hydroxy amides. As expected, other α-hydroxy amides derivatives also showed similar results. Aliphatic and aromatic amides, and the heterocycle thiophene also worked well. The product of thiophene-substituted α-hydroxy amide with morpholine 3q was produced in 70% yield. Aliphatic derivatives 3r and 3s formed their corresponding products in moderate yields of 62 and 59%, respectively, as the reaction remained incomplete.

Previously, TiCl4-assisted substitution reactions were reported to proceed through a carbocation mechanism.[14] Other groups described TiCl4-catalyzed nucleophilic substitutions of alcohol that proceeded via carbocation formation followed by nucleophilic attack.[14a,15] Studies on the detailed mechanism of this direct amination of α-hydroxy amides are now underway.

In summary, we developed a TiCl4-facilitated, ligand/additive-free relatively mild reaction for the direct amination of α-hydroxy amides. Under the optimized reaction conditions, a broad range of amines including primary, secondary and heterocyclic amines, and even primary amides and indoles were found to participate in this transformation, providing the products in moderate to high yields. Different α-hydroxy amides containing aliphatic, aromatic or heterocyclic substituents such as thiophene also worked well.

Answer: A TiCl4-mediated reaction for the direct amination of \xce\xb1-hydroxy amides has been developed. This simple, general, additive/base/ligand-free reaction is mediated by economical TiCl4. The reaction runs under mild conditions. This highly efficient C\xe2\x80\x93N bond formation protocol is valid for diverse amines, including primary, secondary and heterocyclic amines, and even a primary amide and indole.


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:
papillon - lefevre syndrome belongs to a heterogeneous group of skin diseases that are characterized by hyperkeratosis of palms and soles .
papillon - lefevre syndrome is inherited as an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early loss of primary and permanent teeth .
papillon - lefevre syndrome differs from other types of palmoplantar keratoderma in its severe periodontopathy and premature loss of primary and permanent dentition .
papillon - lefevre syndrome was first described in 1924 by papillon m m and lefevre p in two siblings .
fifty percent of the patients with papillon - lefevre syndrome appear to have been derived from consanguineous marriages .
hart et al . , showed that mutations of cathepsin c gene are responsible for papillon - lefevre syndrome and a region of chromosomes ( 11q14 - 21 ) is responsible for this .
an 18-year - old boy reported to the department of periodontology and implant dentistry , bharati vidyapeeth university dental college and hospital , navi - mumbai for the treatment of generalized mobility of teeth and bleeding gums .
scaly skin lesions began to appear by third year of age , later fissures appeared on palms and soles .
intense itching was noted and skin lesions went on to involve fingers , knees and elbows .
patient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .
intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .
hyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1 this patient too showed considerable hyperkeratosis of palms and soles [ figure 6 ] .
orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .
hyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,
thorough scaling and root planing of all teeth was carried out along with administration of systemic antibiotics .
patient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .
intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .
hyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1 this patient too showed considerable hyperkeratosis of palms and soles [ figure 6 ] .
orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .
hyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,
patient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .
intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .
hyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1
orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .
hyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,
thorough scaling and root planing of all teeth was carried out along with administration of systemic antibiotics .
papillon - lefevre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis .
skin lesions develop concurrently with oral lesions and may extend to dorsal surfaces of hands and feet .
another form of disease associated with palmoplantar keratosis and severe aggressive periodontitis has been named haim - munk syndrome .
it differs from papillon - lefevre syndrome in symptoms such as arachnodactyly , acroosterolysis and onychogryphosis . in papillon - lefevre syndrome
the permanent dentition starts to erupt at proper time , but around 8 - 9 years of age periodontal destruction is repeated in the same manner as in primary dentition .
all permanent teeth are usually lost before 14 - 16 years of age . in subjects with papillon - lefevre syndrome
the exact biochemical defect leading to periodontal disease is still unclear . in 1942 , wannenmacher suggested that papillon - lefevre syndrome was due to a combination of ecto and mesodermal malformations .
suggested that a functional imbalance of collagenolytic activity in the periodontal ligament was responsible for periodontitis in papillon - lefevre syndrome . in 1984 , vandyke suggested that neutrophils from an individual with papillon - lefevre syndrome exhibit decreased receptor affinity for chemotaxins such as formyl peptides .
papillon - lefevre syndrome is associated with myeloperoxide deficiency , low integrin expression , defective phagocytosis and chemotaxis .
hattab et al . , reported four cases of papillon - lefevre syndrome affecting two jordanian families with eight children . in all patients there was a relationship between increased severity of skin lesions and seasonal variations and intensified periodontal destruction .
lass et al . in three multiplex families , one ethiopian and two german , demonstrated linkage of papillon - lefevre syndrome with chromosome 11q13-q14 .
fischer et al . , conducted a primary genome wide search by homozygosity mapping in a large consanguineous family with four affected siblings .
toomes et al . , showed that in patients with papillon - lefevre syndrome gene for cathepsin c which lies in chromosome 11 had undergone mutation resulting in decreased cathepsin c production .
hart et al . , reported mutations in cathepsin c gene in patients with papillon - lefevre syndrome from five different countries . in conclusion , we have reported two cases of papillon - lefevre syndrome .
further studies in the field of microbiology and genetics are necessary to find the exact cause of periodontal destruction in such patients , so that best possible dental treatment can be rendered to them .
in subjects with papillon - lefevre syndrome there is defective cathepsin c production . the gene for cathepsin c lies on chromosome 11 .
the exact biochemical defect leading to periodontal disease is still unclear . in 1942 , wannenmacher suggested that papillon - lefevre syndrome was due to a combination of ecto and mesodermal malformations .
suggested that a functional imbalance of collagenolytic activity in the periodontal ligament was responsible for periodontitis in papillon - lefevre syndrome . in 1984 , vandyke suggested that neutrophils from an individual with papillon - lefevre syndrome exhibit decreased receptor affinity for chemotaxins such as formyl peptides .
papillon - lefevre syndrome is associated with myeloperoxide deficiency , low integrin expression , defective phagocytosis and chemotaxis .
hattab et al . , reported four cases of papillon - lefevre syndrome affecting two jordanian families with eight children . in all patients there was a relationship between increased severity of skin lesions and seasonal variations and intensified periodontal destruction .
lass et al . in three multiplex families , one ethiopian and two german , demonstrated linkage of papillon - lefevre syndrome with chromosome 11q13-q14 .
fischer et al . , conducted a primary genome wide search by homozygosity mapping in a large consanguineous family with four affected siblings .
. toomes et al . , showed that in patients with papillon - lefevre syndrome gene for cathepsin c which lies in chromosome 11 had undergone mutation resulting in decreased cathepsin c production .
hart et al . , reported mutations in cathepsin c gene in patients with papillon - lefevre syndrome from five different countries . in conclusion ,
further studies in the field of microbiology and genetics are necessary to find the exact cause of periodontal destruction in such patients , so that best possible dental treatment can be rendered to them .

Answer:
papillon - lefevre syndrome is a rare ( 1 - 4 cases per million ) autosomal recessive disorder showing predominantly oral and dermatological manifestations in the form of aggressive periodontitis affecting both primary and permanent dentition and palmoplantar hyperkeratosis .
 genetic studies have shown that mutations in the major gene locus of chromosome 11q14 with loss of function of cathepsin c gene are responsible for papillon - lefevre syndrome .
 this report presents two siblings with classic signs and symptoms of papillon - lefevre syndrome .
 the exact cause for periodontal destruction in patients with papillon - lefevre syndrome is not known but it is thought to be due to defect in neutrophil function , immune suppression and mutations in cathepsin c gene .


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:
alpha ( )2-adrenoceptor agonists have been used as adjuvant to anesthetic agents in peri - operative period for its several beneficial actions . these drugs improve hemodynamic stability during endotracheal intubation and surgical stress by its central sympatholytic action , and thus reduce anesthetic and opioids requirements .
dexmedetomidine , the pharmacologically active d - isomer of medetomidine , is highly selective and specific 2-adrenoceptor agonist .
the analgesic effect of dexmedetomidine is qualitatively different as compared to opioids and can be used as an alternative to opioids in general anesthesia .
the anesthetic sparing effect of dexmedetomidine demonstrated in earlier studies is confounded by the use of opioids .
opioids , when used as analgesic in general anesthesia , are known to decrease mac value of sevoflurane .
inhalation agents were titrated based on either hemodynamic criteria and/or bispectral index values in studies done earlier , and none of them demonstrated the effect of dexmedetomidine alone on requirement of sevoflurane with the use of entropy as a measure of depth of anesthesia .
the primary objective of our study was to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on sevoflurane requirement during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis .
the study protocol was approved by ethical committee of the institute , and written informed consent was obtained from all patients included in the study .
the study population comprised of 60 patients , aged 18 - 55 years , with american society of anesthesiologists ( asa ) status of 1 and 2 , undergoing major elective surgical procedures .
we excluded patients older than 55 years , those with a history of psychiatric / neurological illness , cardiovascular disease , hypertensive patients , morbid obese patients , pregnant and nursing women , with known allergic reaction to any of the study medication , recent use of sedatives or analgesics , and with significant laboratory abnormalities .
the consenting patients were randomly allocated into one of the two anesthetic groups based on the simple randomization table generated : group a ( control group ) : sevoflurane - fentanyl and group b ( test group ) : sevoflurane - dexmedetomidine .
after arrival in the operating room , glycopyrrolate 0.004 mg / kg and ondansetron 0.15 mg / kg intravenous ( iv ) were given as pre - medication in both the groups .
the patients in group b received dexmedetomidine(2 ml diluted in 48 ml of saline ) iv in a dose of 1 mcg / kg over10 minutes through infusion pump prior to induction .
monitoring consisted of continuous electrokardiogram ( ekg ) , non - invasive blood pressure ( nibp ) , pulse oximetry ( spo2 ) , co2 expired fraction ( etco2 ) , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and electroencephalograph ( eeg ) analysis by entropy ( response and state entropy ) . after the start of drug infusion , heart rate ( hr ) , blood pressure
( bp ) , respiratory rate ( rr ) , spo2 , and entropy were measured at 5 and 10 minute .
patients in group a received fentanyl 2 g / kg intravenous slowly , 2 minutes prior to induction .
after pre - oxygenation for 10 minutes , general anesthesia was induced with thiopentone sodium 5 mg / kg iv slowly .
, dexmedetomidine infusion was continued between 0.2 and 0.8 mcg / kg / h depending on hr , bp , and entropy value changes .
anesthesia was maintained with sevoflurane to a maximum of 2.5% end tidal to maintain heart rate and blood pressure within 20% of baseline value and entropy value between 40 and 60 .
the anesthesiologist was permitted to treat hemodynamic events , defined as heart rate and blood pressure more than 20% of baseline , in spite of increasing sevoflurane concentration to 2.5% and dexmedetomidine infusion to 0.8 mg / kg with supplemental analgesia in the form of fentanyl 1 mcg / kg . if rise in heart rate and blood pressure persisted further after supplementation with fentanyl , anesthesiologist was permitted to administer incremental doses of metoprolol 2 - 5 mg .
ephedrine 5 mg iv was given for fall in heart rate and blood pressure more than 20% of baseline .
in the group b , dexmedetomidine was stopped approximately 15 - 20 minutes before completion of surgery , diclofenac sodium aqueous 1 mg / kg was given iv in both groups at the time of skin closure .
reversal of neuromuscular blockade was achieved with neostigmine 0.05 mg / kg and glycopyrrolate 0.008 mg / kg iv slowly .
tracheal extubation was done when respiration was satisfactory and adequate muscle tone was achieved .

hr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.depth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.end tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis .

hr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .
depth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .
end tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis .
statistical analysis was conducted with epi info software ( version 3.5.3 , 2011 , centers for disease control and prevention , atlanta , ga , usa ) for windows statistical package using unpaired t - test for continuous variables with normal distribution .
the non - parametric kruskal - wallis test was used for variables not normally distributed . for categorical variables , chi - square test was used .
the two groups were similar regarding age , sex , weight , and asa physical status [ table 1 ] .
pre - induction heart rate , systolic and diastolic blood pressures were similar between two groups ( p > 0.05 ) .
the depth of anesthesia as assessed by response entropy ( re ) and state entropy ( se ) was comparable between two groups at all time points during maintenance period ( p > 0.05 ) .
the re and se was maintained between 40 and 60 during the period of observation .
the fisevo concentration was significantly less in group b as compared to the group a at all time points ( p < 0.05 ) [ figure 1 ] .
the average etsevo concentration during anesthetic maintenance was 1.35% and 1.72% in the group b and a , respectively .
a significant decrease of 13% to 33% of etsevo concentration was seen with group b from 5 min to 60 minutes post - intubation ( p < 0.05 ) during surgery [ figure 2 ] .
fraction of inspired sevoflurane at different time interval ( pi - post - intubation , fi - fraction of inspired ) end tidal sevoflurane at different time intervals ( pi - post - intubation ) during anesthesia maintenance , group b showed a statistical significant decrease in heart rate , systolic and diastolic blood pressure from baseline at all time points as compared to the group a ( p < 0.05 ) .
an average 6.5% fall in heart rate from baseline in group b as compared to 3.7% rise in the group a , 8% fall in systolic blood pressure from baseline as compared to 3.6% rise in the group a , and 8.16% fall in diastolic blood pressure from baseline as compared to 3.3% rise in the group a was observed [ figures 3 and 4 ] .
changes in sbp and dbp at various time points post - intubation ( pi - post - intubation , sbp - systolic blood pressure , dbp - diastolic blood pressure ) changes in hr at various time points post - intubation ( pi - post intubation , hr - heart rate ) in our study , none of the patients in either group required supplemental analgesia or anti - hypertensive drugs intra - operatively .
bradycardia was observed in 2 patients in group b within 10 mins post - extubation , which promptly responded to atropine 0.6 mg iv .
the major observation in our study was that dexmedetomidine infusion as an adjuvant in general anesthesia causes decreased requirement of sevoflurane without compromising adequate depth of anesthesia , thus it has anesthetic - sparing property .
a study done on patients undergoing hysterectomy showed a 30% reduction of maintenance concentration of isoflurane .
similarly , a reduction in 35% to 50% in isoflurane concentration with low or high dose of dexmedetomidine was found in a study on healthy human volunteers .
this larger reduction in isoflurane requirement seen as compared to our study might be due to difference in study population ( healthy human volunteers vs. patients posted for elective surgery ) and the type of stimulus ( tetanus nerve stimulus vs. surgical stimulus ) .
the results of our study results are consistent with that of the study done by fragen , et al . in elderly patients , which showed a 17% reduction .
dexmedetomidine by its sympatholytic action decreases heart rate and blood pressure , thus assessing the depth of anesthesia by hemodynamic parameters would be unreliable in evaluating its effect on requirement of inhalational agent . several electroencephalogram - dependent indices such as bispectral index and entropy have been used to measure the depth of anesthesia .
entropy is a useful monitor for measuring the electroencephalographic effects of increasing and decreasing sevoflurane concentration and assessing the depth of anesthesia .
analogous to the bispectral index , entropy displays a high degree of specificity and sensitivity in assessing consciousness during anesthesia . using bispectral index to assess the depth of anesthesia , magalhes et al
. showed decreased requirement of sevoflurane with continuous infusion of dexmedetomidine during general anesthesia . in our study , we used entropy to measure the depth of anesthesia , thereby eliminating the bias of evaluation by hemodynamic parameters as in earlier studies .
use of dexmedetomidine produces intra - operative and post - operative opioids - sparing effect .
dexmedetomidine by its sympatholytic action attenuates symapthoadrenal response to tracheal intubation . in patients undergoing laparoscopic tubal ligation , a 33% decrease in morphine
use post - operatively was observed when dexmedetomidine was used at a dose of 0.4 mcg / kg .
dexmedetomidine when administered as infusion at a dose of 0.5 mcg / kg / h has specific analgesic effect and provides visceral pain relief . in morbidly obese ,
dexmedetomidine produces a greater decrease in sympathovagal balance intra - operatively than fentanyl along with better post - operative analgesia .
dexmedetomidine , when used as sole substitute for remifentanil in ambulatory gynecologic laparoscopic surgery , provides better peri - operative hemodynamic stability and post - operative analgesia .
dexmedetomidine provides similar intra - operative hemodynamic response and better post - operative analgesia compared to remifentanil in patients undergoing supratentorial craniotomy .
use of opioids along with dexmedetomidine would confound its effect on requirement of inhalation agent .
hence , in our study , fentanyl was not administered in dexmedetomidine group b , and we found a 21.5% decrease in the etsevo , in contrast to 33.12% decrease in study done by magalhes e et al . where fentanyl was used .
one limitation of our study was that we included both laparoscopic as well as open surgeries .
to conclude , the continuous infusion of dexmedetomidine , as adjuvant in general anesthesia , significantly decreases the requirement of sevoflurane for maintaining adequate depth of anesthesia .
studies measuring plasma concentration of dexmedetomidine should be undertaken to establish the precise correlation between its dose and inhalational agent 's requirements .

Answer:
background : dexmedetomidine , a 2 agonist as an adjuvant in general anesthesia , has anesthetic and analgesic - sparing property.aims:to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on requirement of sevoflurane during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis.materials and methods : sixty patients were randomly divided into 2 groups of 30 each . in group
 a , fentanyl 2 mcg / kg was given while in group b , dexmedetomidine was given intravenously as loading dose of 1 mcg / kg over 10 min prior to induction .
 after induction with thiopentone in group b , dexmedetomidine was given as infusion at a dose of 0.2 - 0.8 mcg / kg .
 sevoflurane was used as inhalation agent in both groups .
 hemodynamic variables , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and entropy ( response entropy and state entropy ) were continuously recorded .
 statistical analysis was done by unpaired student 's t - test and chi - square test for continuous and categorical variables , respectively .
 a p - value < 0.05 was considered significant.results:the use of dexmedetomidine with sevoflurane was associated with a statistical significant decrease in etsevo at 5 minutes post - intubation ( 1.49  0.11 ) and 60 minutes post - intubation ( 1.11 0.28 ) as compared to the group a [ 1.73 0.30 ( 5 minutes ) ; 1.68 0.50 ( 60 minutes ) ] .
 there was an average 21.5% decrease in etsevo in group b as compared to group a.conclusions:dexmedetomidine , as an adjuvant in general anesthesia , decreases requirement of sevoflurane for maintaining adequate depth of anesthesia .


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:
insulin detemir has now become established as an effective basal insulin preparation and is widely used in the management of both type 1 and type 2 diabetes . although it is similar in efficacy to isophane insulin , we have observed a relative lack of efficacy in two patients with significant hypertriglyceridemia and established nonalcoholic fatty liver disease , suggesting that there are circumstances where the efficacy of detemir may be adversely affected by specific metabolic parameters .
patient 1 was a 56yearold caucasian man with a 4year history of poorly controlled type 2 diabetes and marked hypertriglyceridemia ( random triglycerides were 28.7 mmol / l and total cholesterol was 7.9
his mother had type 2 diabetes , but there was no other family history of note .
he denied alcohol consumption for the previous 14 years and had been only a light drinker previously . at the time of starting insulin
he was being treated with metformin , gliclazide , fenofibrate , and omacor . on examination , he was obese with a body weight of 109 kg and bmi of 32 kg / m .
glycated hemoglobin ( hba1c ) was 69 mmol / mol ( 8.5% ) , fasting triglycerides 8.4 mmol / l , and total cholesterol 4.5 mmol / l .
mol / l ( egfr 102 ml / min/1.73 m ) and liver enzymes were slightly elevated : ast 71
serum albumin was normal 47 g / dl ( 3550 ) , inr 1.04 , and hepatitis serology was negative .
ultrasound confirmed a 17.7cm spleen and ct demonstrated nonalcoholic fatty liver disease ( nafld ) . in view of splenomegaly
, he underwent a bone marrow aspirate and trephine biopsy , both of which were normal .
a liver biopsy confirmed hepatosteatosis with marked steatosis , mild inflammatory activity , and hepatocellular ballooning ( fig .
1a ) . in part of the biopsy , bridging fibrosis with parenchymal nodule formation was in keeping with cirrhotic transformation ( fig .
( b ) reticulin stain ( gordon and sweet ) reveals , in part of the biopsy core , bridging fibrosis with parenchymal nodule formation in keeping with cirrhotic transformation .
insulin detemir ( 14 units nocte ) was commenced as his random glucose values were 1722 mmol / l .
he was using 158 units per day of detemir , in divided doses , plus insulin aspart 24 units with each meal . despite these doses ,
mmol / l and hba1c remained unsatisfactory at 69 mmol / mol ( 8.5% ) .
basal insulin was then changed to insulatard 70 units per day in divided doses ( insulin aspart dose unchanged ) and within four months his hba1c had fallen to 51 mmol / mol ( 6.8% ) and by 12 months he had lost 6 kg of weight .
patient 2 was a 68yearold man with a 20year history of type 2 diabetes and type v hyperlipidemia . for two years , after the diagnosis of diabetes , he was managed with oral hypoglycemic agents alone .
he then developed necrotizing pancreatitis ( considered secondary to hypertriglyceridemia ) and was treated with human isophane insulin and human soluble insulin for ten years before being switched to detemir and novorapid .
he was referred due to the patient 's concern of escalating insulin dose and associated weight gain of 20 kg over the previous five years . at the time of referral the detemir dose was 120 units twice daily and novorapid 120 units with each meal ( total of 600 units / day ) .
he did not drink alcohol . on examination he was obese with body weight of 126 kg and bmi of 44.6 kg / m .
random triglycerides were markedly elevated ( 31.9 mmol / l ) , total cholesterol was 6.3 mmol / l , and hdl was 0.3
there was no clinical or biochemical evidence of any endocrinopathy to explain insulin resistance and no evidence of immunemediated insulin resistance .
liver enzymes and synthetic function were normal but there was mild renal impairment ( serum creatinine 145 mol / l ; egfr 77ml / min/1.73 m ) .
detemir was changed to isophane insulin 100 units bd and novorapid reduced to 100 units / meal .
after six months , the dose of insulatard had stabilized at 140 units bd and novorapid 50 units tds ( 430 units / day  30% reduction in total daily dose ) , his weight remained unchanged and despite the reduction in insulin dose , hba1c improved to 50 mmol / mol ( 6.7% ) .
the two cases presented in this report showed that in patients with a history of severe hypertriglyceridemia and significant fat infiltration of the liver , a hepatoselective insulin ( detemir ) appeared less efficacious in achieving glycemic control .
insulin detemir differs from human insulin by the deletion of the amino acid threonine in position 30 of the b chain , plus the addition of a c14 fatty acid chain at position 29 of the b chain .
this allows detemir to reversibly bind to serum albumin 1 and is a characteristic that has led to it being considered a hepatoselective insulin : the albumin  insulin molecule is unable to pass through the capillary endothelial cell barrier to reach peripheral adipocytes , whereas in the liver , the albumin  detemir molecule is able to pass freely through the sinusoids .
this allows it to exert a greater effect on hepatocytes than in peripheral tissues 2 .
hypothetically , the efficacy of hepatoselective insulin may be reduced in nafld by less hepatic exposure to insulin ( due to increased insulin clearance or to portosystemic shunting ) , or from direct hepatic parenchymal cell damage .
given that the usual action of insulin is to stimulate the liver to store glucose in the form of glycogen and to switch off gluconeogenesis , underexposure of hepatocytes to insulin would lead to hyperglycemia .
a portosystemic shunt was thought to be unlikely in these patients as there were no radiological features of collateral ( variceal ) circulation .
increased clearance of detemir might have occurred ; premarketing studies suggested that hepatic impairment affected the bioavailability of insulin . in these studies
there was a 3547% faster clearance of detemir in patients with severe / moderate liver insufficiency as compared to healthy subjects 3 .
by contrast , clearance of human insulin is usually reduced in liver failure 4 and insulin clamp studies with human insulin have shown decreased clearance in patients with fat infiltration of the liver 5 . in a mouse model of nafld ( induced by highfat feeding ) , there was decreased insulin activation of glycogen synthase and increased gluconeogenesis 6 during a euglycemic  hyperinsulinemic clamp , suggesting a direct , adverse consequence of hepatic fat accumulation .
the closest model available is of detemir 's action in obesity where the presence of nafld may be inferred 7
. a pharmacodynamic study of 18 subjects showed that in the presence of grade 1 obesity ( bmi 3035 kg / m ) a lower glucose infusion rate was required to maintain normoglycemia after administration of detemir , compared to neutral protamine hagedorn ( nph ) insulin or glargine 8 .
advanced hepatocellular fibrosis may be associated with a change in the configuration of the sinusoidal endothelium , including loss of fenestrations , which would reduce the exchanges between hepatocytes and sinusoidal blood .
therefore , this would suggest that in severe nafld / cirrhosis , higher doses of detemir insulin would be required .
an alternative hypothesis is that hypertriglyceridemia may have a direct , adverse effect on detemir action .
the binding of detemir to albumin could be affected by the lipid content of plasma .
competition experiments with fatty acids have shown that levemir can be displaced from human albumin by longchain fatty acids ( containing at least 12 carbon atoms ) but with much weaker competition by a medium chain fatty acid 9 .
the significance of this is uncertain , but potentially it could lead to loss of biological activity , or unpredictable release or clearance of levemir .
antibody development has been observed in phase 3 clinical trials of detemir , but did not impact on metabolic control 10 .
there were no specific features of alternative cause(s ) for a relative lack of efficacy of insulin , such as lysosomal storage disease or monogenic insulin resistance syndromes  and these were not tested for .
it is possible that the cases described relate to less common etiologies of insulin resistance . in managing patients with diabetes , interindividual differences in response to insulin
may be encountered ; a relative lack of efficacy with one type of insulin may not be seen with an alternative insulin .
such a response may be unrelated to the degree of hepatoselectivity of the insulin chosen . in conclusion
, these two cases suggest that detemir may be less efficacious in patients with significant hypertriglyceridemia complicated by nafld .
it is not possible to determine a precise mechanism to explain this observation but this could be due primarily to hypertriglyceridemia or due to the effects of infiltration of hepatic parenchyma with lipid .

Answer:
key clinical messageinsulin detemir is commonly used in obese patients with diabetes mellitus as it is considered hepatoselective and causes less weight gain .
 we describe a relative lack of effectiveness of detemir in patients with significant nafld and hypertriglyceridemia , compared to isophane insulin .
 this may affect how such patients are managed with insulin .


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 clinical effects of toxic alcohols are mainly due to depression of both the central nervous system and myocardial function.1 there are very few published reports of the magnetic resonance imaging ( mri ) features of central nervous system involvement in various types of toxic alcohol poisoning.15 all reports mention cerebral and/or cerebellar toxicity , also known as toxic encephalopathy . there have been no published reports of brain and spinal cord injury secondary to isopropanol ( isopropyl alcohol ) intoxication.15
a 60-year - old caucasian merchant ship captain presented to the emergency department of our hospital with headache , dizziness , and disorientation one day after ingestion of isopropanol along with ethanol ( ethyl alcohol , drinking alcohol ) .
he had celebrated his 60th birthday aboard ship by consuming ethanol and then isopropanol , because ethanol was not available later .
his colleague accompanying him to the hospital brought an empty bottle of rubbing alcohol labelled as 70% volume per volume isopropyl alcohol with a capacity of 473 ml ( one pint ) .
the label on the bottle mentioned its indication for use as a first aid antiseptic and for rubbing and massaging .
the patient s colleague mentioned that the patient had consumed most of the liquid in the bottle and that he ( the colleague ) had consumed a small amount .
the patient s colleague did not give any recent or past history of substance abuse .
an unenhanced computed tomography ( ct ) scan of the brain was performed immediately and was unremarkable .
the patient collapsed in the hospital just 30 minutes after the ct scan was done .
he became deeply comatose with a score of 3/15 on the glasgow coma scale ( a scale to assess central nervous system status where a total score of 15 indicates best and normal outcome ) .
he also developed hypotension , with a blood pressure of 80/40 mmhg , a pulse rate of 65 per minute , and a respiratory rate of 8 per minute .
after administration of intravenous fluids and endotracheal intubation , the patient was admitted to the intensive care department .
blood investigations revealed leukocytosis of 26,000 ( normal 4,00010,000 ) white blood cells per l , a hemoglobin of 15.7 ( normal 1317 ) g / dl , and a mean corpuscular volume of 93 ( normal 83101 ) fl . the initial arterial blood gas report indicated a ph of 6.731 ( normal 7.357.45 ) , a pco2 level of 28.2 ( normal 3548 ) mmhg , a po2 level of 141 ( normal 83108 ) mmhg , a bicarbonate level of 3.5 ( normal 2128 ) mmol / l , and oxygen saturation of 95% ( normal 95%98% ) .
other blood investigations revealed a blood urea nitrogen of 9.5 ( normal 1.78.3 ) mmol / l , serum creatinine of 157 ( normal 62124 ) mol / l , na of 141 ( normal 134146 )
mmol / l , cl of 107 ( normal 96110 ) mmol / l , hco3 of 5 ( normal 2430 ) mmol / l , and capillary blood glucose of 7.2 ( normal 3.35.5 ) mmol / l .
his blood lactic acid level was significantly elevated at 8.7 ( normal 0.52.2 ) mmol / ml .
blood levels of isopropanol and other toxic alcohols ( like methanol , ethylene glycol , propylene glycol , and diethylene glycol ) could not be obtained because the necessary investigations were not available .
investigations repeated at 2-hour intervals revealed increasing renal impairment , hyperglycemia , and electrolyte imbalance ( low bicarbonate levels and hyperkalemia ) .
no growth was detected on cultures of urine and blood , and no crystals were found in the urine on microscopic examination .
the patient received hemodialysis because of severe acidosis and hyperkalemia , which led to gradual improvement in his blood ph and lactic acid levels .
he was also treated with norepinephrine ( as a vasopressor ) and intravenous fluids , but there was no improvement in blood pressure .
he received 500 ml of fractionated plasma protein stat over 30 minutes , 2,000 ml of normal saline over 2 hours , and was then kept on 200 ml / hour of normal saline .
he did not respond to intravenous fluids and within the first 2 hours was started on norepinephrine 10 g per minute , which was gradually increased up to a maximum dose of 90 g per minute .
unenhanced mri scans of the brain and spine performed 6 days after hospital admission showed bilaterally symmetrical hyperintensities on t2-weighted , t1-weighted , t2 * -weighted , fluid attenuated inversion recovery ( flair ) , and diffusion - weighted images in the cerebral and cerebellar cortex and white matter , basal ganglia , thalami , and brainstem ( figures 14 ) . a swollen and edematous cervical spinal cord was noted with t2-weighted and flair hyperintensities within it ( figures 2 and 4 ) .
cerebellar tonsillar herniation of 17 mm was noted to be compressing the proximal cervical cord ( figures 2 and 4 ) .
petechial hemorrhages were noted in the brainstem and the gangliocapsular regions bilaterally ( figure 1 ) .
all the features described above are compatible with toxic brain and cervical spinal cord damage .
finally , the patient expired ten days after hospital admission , despite his improving blood picture .
chemicals involved in alcohol intoxication are ethanol , methanol , isopropanol , ethylene glycol , diethylene glycol , and propylene glycol .
ethanol is considered as a drinking alcohol and the rest as toxic alcohols . among the toxic alcohols ,
isopropanol itself is more toxic than its metabolite ( acetone ) , while the metabolites of the rest of the toxic alcohols are more toxic than the parent alcohol .
isopropanol poisoning is characterized by an increased osmolal gap in the setting of positive serum and urine ketones and does not cause metabolic acidosis , while the rest of the toxic alcohols cause mild to severe metabolic acidosis.1 when not mixed with ethanol or other intoxicants , the signs and symptoms of intoxication may start earlier ( few hours ) after isopropanol ingestion and may be delayed by up to a day or more after ingestion of other toxic alcohols . unlike methanol and ethylene glycol ,
isopropanol is more toxic than its metabolites ; hence , alcohol dehydrogenase inhibitors are not given.1 hemodialysis removes both isopropanol and its metabolite.1 in our case , the clinical and biochemical features were atypical for isopropanol toxicity likely due to coconsumption of ethanol and delayed patient presentation .
ingestion of approximately 200 ml of pure isopropanol can be lethal.1 the patient was managed symptomatically , mainly with hemodialysis .
we wish to emphasize the atypical mri features in this case that have not been reported before in cases of toxic alcohol ingestion . in our case ,
these were likely due to reduced brain perfusion.6 these lesions were bilaterally symmetrical , and the distribution of the affected areas was highly indicative of a toxic injury.6 bilateral involvement of the basal ganglia and thalami has been reported in a few cases of ethylene glycol intoxication . however , cervical spinal cord involvement and cerebellar tonsillar herniation has not been reported before in cases of toxic alcohol ingestion and even in cases of other substance abuse . in humans ,
the opioid receptors are predominantly present in the cerebellum and the limbic systems , thus causing cerebellar - predominant toxicity in cases of opioid intoxication.6 involvement of the basal ganglia is also noticed in a few of these cases.6 a similar explanation may be given in cases of alcohol intoxication . to the best of our knowledge ,
this is the first reported case of cerebral , cerebellar , brainstem , and cervical spinal cord involvement on mri secondary to isopropanol intoxication .
here we present a very rare case of involvement of cerebrum , cerebellum , brainstem , and cervical spinal cord demonstrated on mri after coconsumption of isopropanol and ethanol . to our knowledge ,
involvement of the cervical spinal cord and cerebellar tonsillar herniation after toxic alcohol ingestion have not been reported before in the published literature .

Answer:
a 60-year - old man presented with headache , dizziness , and disorientation one day after consumption of isopropanol along with ethanol . computed tomography ( ct ) of the brain performed immediately was unremarkable .
 the patient collapsed within the hospital 30 minutes after the ct scan was done , and remained comatose until death , showing no improvement with symptomatic treatment .
 magnetic resonance imaging of the brain and spine done 6 days after admission revealed bilaterally symmetrical hyperintensities involving the cerebral and cerebellar cortex and white matter , basal ganglia , thalami , and brainstem on t2-weighted , fluid attenuated inversion recovery and diffusion weighted images ; similar hyperintensities were seen involving the swollen and edematous cervical spinal cord and cerebellar tonsillar herniation compressing the proximal cervical cord .
 petechial hemorrhages were also noted within the brainstem .
 these features are compatible with toxic injury to the brain and cervical spinal cord . to our knowledge ,
 the magnetic resonance imaging features of brain and spinal cord injury and cerebellar tonsillar herniation , secondary to isopropanol intoxication have not been reported in the published literature before .


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:
dilatation of various lengths and severity of the common bile duct ( cbd ) , entitled choledochal cyst , has been detected in utero and usually presents with icterus in infancy , clinically mimicking biliary atresia and neonatal hepatitis1 ) .
younger children and occasionally infants tend to present with painless jaundice , and older children present with recurrent abdominal pain , which was actually due to acute pancreatitis12 ) .
postnatally , ultrasonography ( us ) is the initial diagnostic modality of choice , allowing for precise measurements of intra- or extrahepatic duct dilatation and identification of stones and sludge .
magnetic resonance cholangiopancreatography ( mrcp ) and endoscopic retrograde cholangiopancreatography ( ercp ) has superseded the use of computed tomography ( ct ) for preoperative anatomical delineation of the pancreaticobiliary tract .
here we present the biggest choledochal cyst reported in infancy in the literature to our knowledge .
a term female baby was born by normal delivery route after consanguineous marriage , at house , in syria as the 6th child of her parents .
this family was living the civil war in syria at that time . during 4 months period abdominal distension had increased . because of restlessness and growing abdominal distension
but as a result of investigations they were sent home because of normal laboratory results . after 15 days they admitted to hospital because of jaundice and abdominal cyst
she had referred to our hospital ( in turkey ) with the preliminary diagnosis of abdomianl cyst and hepatitis developed due to compression of cyst . on her admission ,
us revealed giant abdominal cyst with thin wall and liquid - debris level extending from right upper quadrant to pelvic region .
it was suspected that bile duct 's dilatation was due to abdominal giant cyst 's pressure .
she was operated with the differential diagnosis of duplication , omental or mesenteric cyst . at operation , a giant type 1a choledochal cyst , 160 mm in diameter , was surprisingly detected ( fig .
serum levels of bilirubin decreased sharply and the patient was discharged without any problems on the tenth postoperative day .
a choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts2 ) .
type ia is a cystic dilation of the cbd ; type ib is a focal segmental dilation of the distal cbd ; type ic is a fusiform dilation of both the common hepatic duct and cbd . in type ii , the cyst forms a diverticulum from the extrahepatic bile duct .
type iii , also known as choledochocele , is a dilation of the distal cbd lying mainly within the duodenal wall .
type iv is essentially type i anatomy with either intrahepatic bile duct cyst ( iva ) or choledochocele ( ivb ) .
some authors refer to caroli 's disease with multiple cystic dilations of the intrahepatic biliary tree as type v23 ) . in our case
there was a cystic dilation of the cbd as a type ia choledochal cyst with minimal dilatation of intrahepatic bile ducts .
this malformation primarily affects girls ( 4:1 ) and about 80% become symptomatic during childhood .
choledochal cysts remain relatively uncommon in western europe and the united states , although they are appreciably more common in asia .
obstructive jaundice is the main presentation symptom in children , but abdominal pain is the commonest symptom in adults .
the classical triad of pain , jaundice and a palpable mass is uncommon , occurring in no more than 6% in one uk series4 ) .
the complications of congenital cystic dilatation of the bile duct are biliary stone formation , progressive biliary cirrhosis with portal hypertension , and carcinoma .
fusiform lesions are never large enough to be palpable while multiple intrahepatic type 4 lesions cause predisposition to stone formation and sepsis .
a wide variety of imaging techniques are available which noninvasively reconstruct biliary anatomy and give an excellent idea of biliary function .
although us is the first described imaging method to determine the cbd cyst , ct , mrcp , and ercp are superior to assess the extention of the cyst and associated pathologies such as cholangitis , pancreatitis and pancreaticobiliary junction anomaly . in our case , we used us and ct to identify the abdominal mass ' origin . because of the diameter of the cyst , cbd cyst was not thought in the differential diagnosis .
cbd malformations should be kept in mind as a differential diagnosis of the cystic mass regardless of size , and patient 's age .
surgery is the main choice of treatment but some centres in south american and asia have reported ercp and sphincterotomy alone as definitive treatment for mild fusiform dilatation although their long - term prognosis is not known3 ) . at operation , it was difficult to make the differential diagnosis of our giant cyst .
it was important to make the dissection of the cyst carefully in order to avoid the iatrogenic injury .
following the diagnosis of choledochal cyst was confirmed , hepaticojejunostomy was easier depending on the wide common hepatic duct of our huge cyst .
tang et al.5 ) reported a study that involves 62 children ( average age of 2.3 years ) who had cysts with the average diameter of 42 mm ( range , 12158 mm ) .
there is no information about the child'a age with the 158-mm cyst . as our knowledge we report the biggest choledocal cyst case in infancy in the literature . in conclusion ,
cbd malformations should be kept in mind as a differential diagnosis at the cystic mass regardless of cyst 's size , and patient 's age , especially in children presented with abdominal pain , jaundice , and palpable mass .

Answer:
choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts .
 postnatally , ultrasonography is the initial diagnostic modality of choice , allowing for precise measurements of intra- or extrahepatic duct dilatation and identification of stones and sludge .
 symptoms depend on the age at presentation .
 common bile duct malformations should be considered as a differential diagnosis of a cystic mass regardless of the cyst 's size or patient 's age , especially in children presenting with abdominal pain , jaundice , and palpable mass . to the best of our knowledge ,
 we report the largest choledochal cyst in infancy .


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:
as a national reference center for q fever , our center receives samples from france and other regions for serologic , molecular , histologic , and immunohistochemical analyses as described ( 57 ) .
in 2012 , we received a cardiac valve sample from a patient in cayenne with q fever endocarditis who had undergone surgery in martinique . in the same year , we collected 4 heparinized blood samples from patients with acute q fever from cayenne that were collected before initiation of antimicrobial drug treatment .
serologic titers of igg1 increased to 51,200 in this patient , and results of quantitative pcr ( qpcr ) and immunohistochemical analyses of the valvular sample were positive for c. burnetii ( figure 1 ) .
the other 4 patients ( 2 men and 2 women ) had fever and acute pneumonia , and 2 of them also had increased transaminase levels .
the heparinized blood samples were tested by using a specific qpcr ; samples from only 1 patient were positive for c. burnetii .
immunohistochemical detection of coxiella burnetii in resected cardiac valve of a 60-year - old man with q fever endocarditis , cayenne , french guiana .
we successfully cultured c. burnetii from the valvular sample after incubation for 16 days and from 3 blood samples after incubation for 25 , 32 , and 32 days .
paradoxically , the only blood sample that was positive by qpcr was negative by culture .
spacers cox 51 and cox 20 were the most discriminating spacers in identifying this genotype , and the 3 isolates from the blood cultures were also identified by these 2 spacers as genotype 17 ( figure 2 ) .
this genotype had been identified in our laboratory only once , in 2000 in an aortic valve of a 40-year - old french man who had undergone surgery in france , had q fever endocarditis , and was co - infected with streptococcus oralis .
retrospectively , we found that patient had lived in cayenne for years before his diagnosis with q fever endocarditis .
therefore , all genotype 17 isolates were obtained from who lived or had lived in cayenne , making it unique to this area .
we determined the antimicrobial drug susceptibilities of these isolates , and the mic of doxycycline was 0.25 g / ml for all isolates ( 10 ) .
phylogenetic diversity of 34 genotypes of coxiella burnetii identified by using multispacer sequence typing ( mst ) .
scale bar indicates nucleotide substitutions per site . for the past 10 years , routine cell culture for c. burnetii has been performed in our laboratory .
we found that the proportion of isolates obtained from blood samples of patients with acute q fever was higher for patients from cayenne than for patients from metropolitan france .
we obtained 3 isolates from 5 blood samples from untreated patients in cayenne and 3 isolates from 65 samples from patients in metropolitan france ( p = 0.003 , by fisher exact test ) .
however , we did not find any difference with respect to the culture delay between patients from the 2 locations .
our work shows that genotype 17 , a unique genotype , is circulating in cayenne .
this genotype is related to genotypes that harbor the qph1 plasmid , which causes the most severe clinical forms of acute q fever in experimental animal models ( 11,12 ) .
only bacteria from this group and bacteria containing the qpdv plasmid have been found in cases of human acute q fever ( 9,13 ) .
we believe that severity of q fever infection is related to the strain of c. burnetii circulating in cayenne . because the population in french guiana is a large diversity of creole , amerindian , maroon , caucasian , and asian persons ( 14 ) , we excluded the hypothesis that genetic susceptibility of patients from cayenne to c. burnetii infection might be related to severity of the disease .
we observed a higher rate of strain isolation from the blood of patients from cayenne than from the blood of patients from metropolitan france .
this difference may be related to a higher bacterial load in blood or a greater ability of the bacteria to grow on cell cultures .
this second hypothesis seems more likely because even if the observed delay for the first culture was the same for genotype 17 and other genotypes , the strain from cayenne was isolated more frequently in the cell line that we used ( hel cells ) than other strains of c. burnetii from france . in addition , we did not find a higher number of dna copies in the blood of patients from cayenne , and qpcr results were not correlated with culture results . c. burnetii isolates from cayenne were susceptible to antimicrobial drugs , particularly doxycycline .
these isolates cause acute pneumonia and endocarditis . among the 34 genotypes identified in our study by multispacer
a larger biodiversity of strains has been observed in samples from patients in metropolitan france ( 9 ) , where 21 genotypes circulate ( figure 2 ) .
in contrast , during the recent q fever outbreak in the netherlands , it appears that a single strain ( genotype 33 ) was responsible for the epidemic ( 15 ) .
we believe that there has been an epidemic developing in cayenne since 1996 that is caused primarily , if not solely , by a single strain that has circulated since at least 2000 , whose reservoir is unknown ( 1,2 ) . in conclusion ,
c. burnetii genotype 17 is circulating in french guiana and causing acute infections and endocarditis .
this strain is epidemic and most likely causes more acute infections with exacerbated immune responses than other known genotypes of c. burnetii .

Answer:
acute q fever is an emergent and severe disease in french guiana .
 we obtained 5 coxiella burnetii isolates from samples of patients from cayenne and found an epidemic clone circulating in cayenne .
 this clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains .