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 epidemic of human immunodeficiency virus / acquired immunodeficiency syndrome ( hiv / aids ) is in its third decade and has reached to alarming proportions worldwide . according to the centers for disease control and prevention , more than one million people are living with hiv with an estimated 56,300 infections happening each year in the united states .
men who have sex with men ( msm ) population account for more than half ( 53% ) of all the new hiv infections , and blacks represent almost half ( 46% ) of people living with hiv in the united states.1 most of the hiv - related research is targeted towards high - risk groups such as prostitutes , gays and substance abusers but there is evidence that it is increasing in college students and adolescents as well.23 in 33 states with confidential name - based hiv reporting , of the 17,824 persons 13 - 24 years of age , 62% were males and 38% were females.2 an early step in preventive hiv counseling is behavioral risk assessment especially among high risk individuals in resource - limited settings.4 psychosocial stabilization as a means of coping among hiv infected individuals can not be overemphasized .
besides the trained hiv counselors , family physicians , who are trained in psychosocial and community medicine , are equally poised to meet this demand.5 patient - provider relationships , when it comes to hiv positive patients , are ironically constrained as risk - reduction counseling falls woefully short of required percentage.6 si - milarly , counseling for hiv positive individuals who are on treatment for maintaining treatment adherence is quite poor.7 some of the barriers may be providercentric , such as dealing with emotional issues surrounding hiv and doubtfulness of providing good care.8 these barriers faced by counselors need to be addressed by techniques such as interactive counseling , motivational interviewing and application of stages of change.9 the usa preventive services task force made a recommendation few years back of counseling all adolescents and adults about risk reduction after they have been advised about risk factors for hiv infection and sexually transmitted diseases,10 and sexual history taking.11 some of the risk factors for engaging in unsafe sexual activities among the college students are use of alcohol,12 partner characteristics such as age,13 and substance abuse.14 the determinants of safer sex in adult population vary from whether they are hiv positive males , hiv positive females , gay or a bisexual population .
the risk factors in a study which looked at hiv positive gays and bisexuals were mainly unprotected anal sex , which has a higher risk of hiv transmission . some of the strategies tried in this population were problem solving exercises that attempt to increase perceived benefits of safer sex .
counselors also made the participants aware of alternative to regular use of male condoms.15 the reason for engaging in unsafe sexual practices especially in this gay population was pleasure seeking .
some of the barriers for attaining safer sex are inaccurate risk perception , and gender inequalities , like women being powerless to negotiate their sexual safety.16 risk perception can be improved by using social interactions .
social network formation which includes spousal communication related to aids risk has been proven to improve diffusion of behavioral change through the society.17 protection from getting hiv / aids consists of abstinence , consistent and correct condom usage and having just one sexual partner ( monogamy ) .
several studies have found that pregnancy prevention rather than disease prevention was the impetus for condom use.1819 health education in the form of information about pregnancy prevention can unintentionally increase condom use .
it was found that nigerian undergraduates , who had very good knowledge about hiv / aids , had low condom use to prevent its transmission.19 further evidence of knowledge - behavior gap comes from a study , which used a random sample survey of students in which the level of student knowledge was very high but did not lead to protective condom behaviors .
however , knowledge was found to be an enabling factor in maintaining a comfort level when asking partners about their sexual histories and in requesting their partners to take an aids test.20 in a pilot project , which looked at the effect of hiv / aids prevention related messages in improving protective behaviors among indonesian participants , it was found that those exposed to the intervention were significantly more likely to use condoms to avoid aids .
they also felt that these messages had a great impact on them to a point of wanting to change their lifestyle.21 this study did not show conclusively that there was actual behavior change on part of the participants .
this helps to conclude that hiv / aids education related programs are not enough for generating a behavior change and can help in awareness of the disease to certain extent .
furthermore , from the point of view of clarifying risk perception , one needs to provide counseling which includes risk reduction or harm reduction as its integral part .
the purpose of this review is to address a number of counseling strategies used for education and counseling of individuals at risk of getting hiv / aids .
moreover , later in this paper are discussed some of the counseling strategies used in individuals already diagnosed with hiv or aids and these strategies were used in preventing further transmission of the disease .
in order to collect materials for this review , a detailed search of cinahl , medline , eric , academic search premier , scopus , web of science , and social sciences citation index databases was carried out for the time period 1995 - 2010 . a boolean search strategy where the key words entered for search were  counseling  and  strategies  and  hiv / aids  and  hiv/ aids  and  counseling  in differing orders was used to extract studies related to counseling skills and strategies for risk reduction as well as strategies in hiv positive people .
hiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .
it consists of dealing with a variety of issues such as medical , psychological and social .
client - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word
client - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,
the risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .
results showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27 counseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .
motivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique
, the health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .
a meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31
hiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .
it consists of dealing with a variety of issues such as medical , psychological and social .
client - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word
client - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,
the risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .
results showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27 counseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .
motivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique ,
the health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .
a meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31
hiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .
it consists of dealing with a variety of issues such as medical , psychological and social .
client - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word
client - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,
the risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .
results showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27
counseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .
motivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique
, the health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .
a meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31
there are several examples of one - on - one counseling methods used for risk reduction counseling among hiv positive individuals .
the various dimensions touched upon were use of a negative approach,31 assessing readiness to change,32 and motivational enhancement therapy.33 hence , we see multiple approaches used by counselors in providing education and prevention counseling to  at risk individuals and also individuals who have been infected with the virus .
internet - based counseling has gained some popularity over recent years but has to deal with issues such as lack of visual and verbal cues , confidentiality , accessibility problems by those in great need and increased client separation.34 counseling related to using spiritual coping techniques have been well established in cancer literature but has limited evidence in hiv related counseling .

Answer:
objectives : the human immunodeficiency virus / acquired immunodeficiency syndrome ( hiv / aids ) epidemic is in its third decade and has reached to alarming proportions worldwide . according to the centers for disease control and prevention , more than one million people are living with hiv with an estimated 56,300 infections happening each year in the united states .
 diagnosis of hiv / aids via early testing along with pretest and post - test counseling is important for psychosocial stabilization and destigmatization .
 risk reduction counseling as a preventive counseling method is equally important in high - risk individuals such as adolescents , substance abusers and in gay and bisexual population .
 the purpose of this review is to address a number of counseling strategies used for education and counseling of individuals at risk of getting hiv / aids and also among those who are hiv-infected.methods:in order to collect materials for this review , a detailed search of cinahl , medline , eric , academic search premier , scopus , web of science and social sciences citation index databases was carried out for the time period 1995-2010.results:some of the various dimensions of counseling are negative approach counseling , assessing readiness to change , and motivational enhancement therapy.conclusions:multiple approaches are used by counselors in providing education and prevention counseling to  at risk individuals and also individuals who have been infected with the virus .
 no one method is superior to another and some gamut of techniques are practiced by hiv / aids counselors .


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:
most cases were reported in patients with chronic liver disease and cancer , and cases of s. algae infection in end - stage renal disease ( esrd ) patients are few .
the problems related to clinical practice are that little is known about the etiology of s. algae infection in esrd patients and that this bacterium is often confused with shewanella putrefaciens , although these two species may have different pathogenicities in humans .
we herein report a case of s. algae bacteremia in a patient with esrd and review previous case reports on shewanella infection in esrd patients .
a 71-year - old man was admitted to our hospital in mid - july because of a 5-day history of nausea and abdominal pain .
he had been diagnosed with chronic kidney disease ( ckd ) due to chronic glomerulonephritis and had had an arteriovenous fistula in his left arm in preparation for renal replacement therapy since two month prior to the onset .
he had been given an erythropoiesis - stimulating agent ( esa ; darbepoetin alpha 180 g / month ) for renal anemia ; he was not on any iron supplements .
the laboratory data 1 month before the onset of symptoms showed hemoglobin of 6.9 g / dl , fe of 141 g / dl , transferrin saturation ( tsat ) of 76.6% , and ferritin of 704 ng / ml , findings that were indicative of dysregulated iron metabolism .
he had eaten sliced raw fish or  sashimi  of mackerel and squid three days before the manifestations of nausea and abdominal pain , for which he visited the outpatient unit , where he was diagnosed with infectious enterocolitis and was given oral fosfomycin .
however , his symptoms worsened , and he was admitted to our hospital five days after the onset of symptoms .
a physical examination showed that his blood pressure was 160/70 mmhg , heart rate 83 beats / min , and body temperature 39.5. he had abdominal tenderness without rebound tenderness .
laboratory tests on admission showed a white blood cell count of 3,700 /l with 83% segmented neutrophils , hemoglobin of 7.6 g / dl , mean corpuscular volume ( mcv ) of 93.4 fl , mean corpuscular hemoglobin ( mch ) of 30.2 pg , mean corpuscular hemoglobin concentration ( mchc ) of 32.5 g / dl , and platelet count of 156,000 /l .
serum chemistries showed serum sodium 134 meq / l , potassium 5.0 meq / l , chloride 91 meq / l , calcium 5.0 mg / dl , phosphorus 11.7 mg / dl , magnesium 1.6 mg / dl , uric acid 11.8 mg / dl , blood urea nitrogen 166.9 mg / dl , creatinine 23.0 mg / dl , total protein 6.8 g / dl , albumin 2.8 g / dl , aspartate aminotransferase 27 u / l , alanine transaminase 19 u / l , lactate dehydrogenase 882 u / l , alkaline phosphatase 210 u / l , -glutamyl transpeptidase 19 u / l , creatine kinase 1,809 u / l , and c - reactive protein 11.7 mg / dl . abdominal computed tomography ( ct ) revealed intestinal swelling and fluid collection , compatible with infectious enterocolitis ( figure ) . a , b : abdominal computed tomography on admission revealed intestinal swelling and fluid collection , compatible with infectious enterocolitis .
two sets of blood cultures were collected before cefmetazole ( 1 g / day ) was started . on the second hospital day , he went into cardiac arrest ; cardiopulmonary resuscitation resulted in the return of spontaneous circulation .
antimicrobial therapy was changed to meropenem ( 2 g / day ) . on the third hospital day ,
gram - negative bacteria appeared in both sets of the blood culture obtained on admission and were identified as s. putrefaciens 4 days later .
ceftazidime ( 2 g / day ) was given based on the susceptibility test ( table 1 ) .
mic : minimum inhibitory concentration his condition improved ; therefore , continuous hemodiafiltration was switched to hemodialysis 3 times per week .
on the 13th hospital day , the antimicrobial agent was changed to levofloxacin and continued for 1 week .
he was discharged on the 26th hospital day without any complications and continued maintenance hemodialysis .
the bacterium recovered from the blood culture was further analyzed because the patient 's condition had deteriorated . a 16s rrna gene sequence analysis revealed that the bacterium was s. algae
s. algae is a rare causative pathogen of bacteremia , skin and soft tissue infection , or hepatobiliary infection .
we reported a case of s. algae bacteremia in an esrd patient and demonstrated the probable link between raw seafood consumption and shewanella infection .
this patient had iron overload that was related to a dysregulated iron metabolism caused by esrd .
raw seafood consumption by an esrd patient may be a risk factor for shewanella infection .
shewanella species are gram - negative bacteria that are mainly isolated from the marine environment .
this species was once named pseudomonas putrefaciens ; it was originally classified in the family vibrioneceae until the 1990s , when it was reclassified as genus shewanella ( 1 ) .
most case reports of shewanella infection have described an association with exposure to seawater ; such contact can cause ear infection , skin or soft tissue infection , and bacteremia ( 1 - 3 ) .
two species , s. putrefaciens and s. algae , have been reported to be pathogenic in humans ( 1 ) .
it is often difficult to distinguish between these two species , because automated identification systems only include the database of s. putrefaciens , but not s. algae ( 2 ) .
therefore , some authors have suggested that the previously reported s. putrefaciens infections may have actually been caused by s. algae , which is thought to be more virulent ( 3 ) . the accurate distinction between these two species requires a 16s rrna gene sequence analysis or phenotypic tests ;
s. algae can only grow at 42 and in 6% nacl ( 1 ) . in the present case , an automated identification system ( microscan walkaway 96 plus , siemens healthcare diagnostics , tokyo , japan ) initially determined the bacterium to be s. putrefaciens ; however , a 16s rrna gene sequence analysis confirmed the bacterium to be s. algae .
shewanella infection can be fulminant and fatal and is often misdiagnosed as vibrio vulnificus infection , because of the similarities in their clinical manifestations ( 2,4 ) .
patients with underlying diseases , such as hepatobiliary disease or malignancy , were reported to be predisposed to shewanella infection , as well as to v. vulnificus infection ( 3 ) ; the mortality rate of shewanella bacteremia was increased in these patients ( 5 ) .
shewanella species belong to the microflora of the marine environment , and exposure to seawater was reported to be one of the risk factors for shewanella infection , especially in temperature regions ( 3 ) .
therefore , more attention should be paid to the pathogenicity of this bacterium , especially in patients with underlying diseases who are exposed to these environments .
there have been seven previously published case reports on shewanella infection in esrd patients ( 4,6 - 11 ) ( table 2 ) .
two cases were reported to be caused by s. algae and four cases by s. putrefaciens ; however , only two cases were further analyzed by a biochemical procedure .
the most common route of infection was skin ulcer ( 3 cases ) , followed by catheter - related infection ( 2 cases ) ; no case was related to oral intake of seafood . in the present case ,
the onset of symptoms was related to seafood consumption , and abdominal ct scan showed signs of infectious enterocolitis .
therefore , we concluded that the shewanella infection in this patient was probably caused by dietary intake of raw fish or  sashimi  .
this was the first case of s. algae infection that might have been transmitted orally in an esrd patient .
esrd : end - stage renal disease , flux : flucloxacillin , gm : gentamicin , pipc : piperacillin , cpfx : ciprofloxacin , cez : cefazolin , lvfx : levofloxacin , mino : minocycline , cfpm : cefepime , caz : ceftazidime , mepm : meropenem , vcm : vancomycin , doxy : doxycycline , drpm : doripenem , amk : amikacin although the reason why the esrd patient was predisposed to shewanella infection is still unclear , dysregulated iron metabolism may be a risk factor for this patient .
iron is not freely available , since it binds to transferrin in the blood ( 12 ) .
pseudomonas and vibrio species have the ability to produce siderophore , which plays an important role in supplying iron to bacteria ( 12,13 ) .
siderophore has a high affinity to iron and is able to displace iron from transferrin .
s. algae was reported to produce siderophore and was capable of absorbing iron into its body ( 14 ) .
patients with hepatobiliary diseases who are susceptible to s. algae often had the complication of iron overload .
the association between shewanella infection and hepatobiliary diseases may be due to iron overload ( 5 ) . in the present case
, the patient did not have hepatic dysfunction but did have esrd with a dysregulated iron metabolism ; his anemia was esa - resistant , and there seemed to be excessive iron levels , although he was not taking any iron supplement .
it was suspected that uremia of the patient contributed to the esa - resistant anemia , because the patient was just starting renal replacement therapy , and the serum creatinine level on admission was extremely high .
recent studies have demonstrated that hepcidin , which reduces iron release from reticuloendothelial and hepatocyte stores , plays an important role in the disordered iron metabolism of uremia including esa resistance ( 15,16 ) .
the serum hepcidin level is related to the residual renal function and elevates in ckd and in esrd patients ( 15,17 ) .
serum hepcidin can be removed by renal replacement therapy ( 18 ) , and insufficient hemodialysis is known to cause esa - resistant anemia ( 19 ) . therefore
, we speculated that the esrd , especially the accompanying iron overload , might have been a risk factor for shewanella infection in this patient . to our knowledge ,
no previous report has described the status of iron metabolism in the esrd patients with shewanella infection .
the limitation of this report was that the data for serum ferritin and tsat on admission were not available .
however , we measured both of these markers at one month before the onset , when the patient was in a stable condition without acute inflammation or infection .
iron status should be evaluated based on ferritin and tsat in ckd and esrd patients ( 19,20 ) .
the ferritin level and tsat of the patient in the present study were compatible with iron overload ( 21,22 ) .
in addition , we were unable to recover s. algae from a stool culture on the eighth hospital day , when the patient had already received courses of an antimicrobial agent to which the bacterium was susceptible .
we could not collect a stool sample at an earlier time , such as at admission , because of the patient 's critically ill condition . in conclusion , we reported a case of s. algae bacteremia that was probably caused by oral intake of raw fish in an esrd patient .
in addition , a dysregulated iron metabolism in esrd may be a risk factor for shewanella infection .

Answer:
a 71-year - old man was admitted because of nausea and abdominal pain .
 he was receiving an erythropoiesis - stimulating agent for anemia and dysregulated iron metabolism due to stage g5 chronic kidney disease .
 he had a history of raw fish intake and was diagnosed with infectious enterocolitis , which worsened and led to septic shock .
 shewanella putrefaciens grew in the blood culture , but shewanella algae was identified in a 16s rrna gene sequence analysis .
 we herein report a case of s. algae bacteremia believed to have been transmitted orally .
 we also reviewed previous case reports on shewanella infection in end - stage renal disease patients .


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:
eligible subjects were healthy individuals who voluntarily received routine comprehensive health check - ups , including computed tomography ( ct ) scan analyses of abdominal adipose tissue , from january to december 2008 at the seoul national university hospital healthcare system gangnam center .
data were collected through a questionnaire , anthropometric measurements , blood samples , and ct scans .
detailed descriptions of the method used for the measurement of abdominal adipose tissue have been published previously ( 8) . in brief , a 5-mm thick umbilical level abdominal section from 16-detector row ct imaging of the abdomen was obtained .
the cross - sectional area ( cm ) of the abdominal fat was calculated using rapidia 2.8 ct software ( infinitt , seoul , korea ) .
the vat area was defined as intra - abdominal fat bound by parietal peritoneum or transversalis fascia , and the sat area was calculated by subtracting the vat area from the total adipose tissue area . because of the high colinearity between sat and vat , adjustments to the regression model or stratification of vat are insufficient to control for the effects of vat on sat .
the ratio between sat and vat ( sat / vat ratio [ svr ] ) was therefore calculated and used in the current study .
mets was defined according to the modified national cholesterol education program adult treatment panel iii ( 9 ) and asia - pacific abdominal obesity criterion ( 10 ) . means with 95% ci and
numbers of participants ( % ) with metabolic risk factors were compared across the svr quintiles .
we used multivariate logistic regressions to evaluate the association between mets and svr after adjusting for age , smoking , alcohol consumption , bmi , menopausal status , and hormonal replacement therapy ( women only ) .
data are expressed as odds ratio ( or ) [ 95% ci ] ; and p for trend .
detailed descriptions of the method used for the measurement of abdominal adipose tissue have been published previously ( 8) . in brief , a 5-mm thick umbilical level abdominal section from 16-detector row ct imaging of the abdomen was obtained .
the cross - sectional area ( cm ) of the abdominal fat was calculated using rapidia 2.8 ct software ( infinitt , seoul , korea ) .
the vat area was defined as intra - abdominal fat bound by parietal peritoneum or transversalis fascia , and the sat area was calculated by subtracting the vat area from the total adipose tissue area . because of the high colinearity between sat and vat , adjustments to the regression model or stratification of vat are insufficient to control for the effects of vat on sat .
the ratio between sat and vat ( sat / vat ratio [ svr ] ) was therefore calculated and used in the current study .
mets was defined according to the modified national cholesterol education program adult treatment panel iii ( 9 ) and asia - pacific abdominal obesity criterion ( 10 ) .
means with 95% ci and numbers of participants ( % ) with metabolic risk factors were compared across the svr quintiles .
we used multivariate logistic regressions to evaluate the association between mets and svr after adjusting for age , smoking , alcohol consumption , bmi , menopausal status , and hormonal replacement therapy ( women only ) .
data are expressed as odds ratio ( or ) [ 95% ci ] ; and p for trend .
forty percent of men and 25% of women had elevated blood pressure , 31% of men and 15% of women had elevated fasting glucose , and 25% of men and 14% of women had mets .
the mean sat and vat areas were 139.8 cm and 134.4 cm in men and 173.1 cm and 80.0 cm in women , respectively .
the prevalence of elevated fasting glucose , elevated triglycerides ( tgs ) , and reduced hdl cholesterol ( hdl - c ) significantly decreased as the svr quintile increased ( 26 , 16 , and 37% in quintile 1 vs. 5 , 4 , and 11% in quintile 5 , respectively ; all p for linear trend < 0.05 ) robust linear decreases in these risk factors were also seen among men ( supplementary table 1b ) .
ors of mets significantly decreased across all 5 quintiles of the svr after adjusting for covariates in both men ( or 1.0 for quintile 1 vs. 0.5 in quintile 5 ; 95% ci 0.30.7 for quintile 5 ; p for linear trend < 0.01 ) and women ( or 1.0 for quintile 1 vs. 0.2 in quintile 5 ; 95% ci 0.10.5 for quintile 5 ; p for linear trend < 0.01 ) ( table 1 ) .
unadjusted and adjusted ors and 95% ci from logistic regressions predicting the likelihood of mets for each of the svr quintiles * adjusted ors take into consideration age , smoking , alcohol consumption , bmi , and menopausal status , hormone replacement therapy ( women only ) .
ors of mets significantly decreased across all 5 quintiles of the svr after adjusting for covariates in both men ( or 1.0 for quintile 1 vs. 0.5 in quintile 5 ; 95% ci 0.30.7 for quintile 5 ; p for linear trend < 0.01 ) and women ( or 1.0 for quintile 1 vs. 0.2 in quintile 5 ; 95% ci 0.10.5 for quintile 5 ; p for linear trend < 0.01 ) ( table 1 ) .
unadjusted and adjusted ors and 95% ci from logistic regressions predicting the likelihood of mets for each of the svr quintiles * adjusted ors take into consideration age , smoking , alcohol consumption , bmi , and menopausal status , hormone replacement therapy ( women only ) .
the purpose of this study was to assess the cross - sectional correlation of abdominal sat with mets in a korean study population .
we found that as the svr increased , mets components such as reduced hdl - c , elevated tgs , and elevated fasting glucose decreased in both sexes . furthermore , this relationship was maintained even after the adjustment for a variety of variables .
small adipocytes in sat play the role of powerful buffers , uptaking circulating free fatty acids and tgs in the postprandial period .
but if they lose their function in adipogenesis or fat storage capacity in sat , fat begins to accumulate in tissues not suited for lipid storage such as vat .
peroxisome proliferatoractivated receptor- ( ppar- ) agonists stimulate the differentiation of adipocytes , resulting in increased accumulation capacity in sat ( 12 ) .
the ppar- coactivator 1 mrna expression is significantly higher in subcutaneous fat than in omental fat ( 13).this mechanism explained the finding that treatment with thiazolidinedione improves insulin sensitivity ( 6 ) . vat and sat differ in cytokine secretion profile such as leptin , adiponectin , interleukin-6 , interleukin-8 , plasminogen activator inhibitor 1 , and angiotensin , which may play some role in the development of mets ( 14,15 ) .
longitudinal associations of vat / sat change with mets , and with leptin and/or adiponectin level should be the focus of future studies .
gluteofemoral sat , which may act as a confounding factor , was not considered in the study .
however , the current study included the analysis of a large dataset of ct - measured sat and vat .
moreover , the study population was generally healthy , which implies that the results can be applied to the general korean population .

Answer:
objectivethis study aimed to assess the correlation between abdominal subcutaneous adipose tissue ( sat ) and metabolic syndrome ( mets ) in korean adults after adjusting for the effects of visceral adipose tissue ( vat).research design and methodsthe sat / vat ratio ( svr ) was calculated using abdominal computed tomography in 2,655 subjects .
 we used regression analyses to assess whether the svr predicted mets.resultsfor both sexes , the prevalence of elevated triglycerides , reduced hdl , and elevated fasting glucose significantly decreased with increasing quintiles of svr ( p for trend < 0.05 ) . the prevalence and odds ratios of mets significantly decreased as the svr increased ( men : odds ratio 0.5 [ 95% ci 0.30.7 ] ; women : 0.2 [ 0.10.5 ] for comparisons of lowest vs. highest quintile ; p for trend < 0.05).conclusionsafter adjustment for vat , abdominal sat was inversely correlated with the occurrence of mets .


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:
in a recent issue of critical care , meyer and colleagues   report interesting surveillance data from icus in 30 german hospitals , based on a large amount of microbiology and pharmacy data gathered between 2001 and 2008 .
one of the main study findings is a decreasing rate of methicillin - resistant staphylococcus aureus ( mrsa ) and a dramatic increase of third generation cephalosporin ( 3gc ) resistant enterobacteriaceae over the study period . in recent years
, most european countries have succeeded in reducing the burden of disease caused by mrsa .
this progress has , however , been partly off set by the increase across europe in the prevalence of multiresistant gram - negative pathogens producing extended - spectrum betalactamases ( esbls ) or carbapenemases .
the current study confirms this worrisome finding and also shows an increase in carbapenem , 3gc and fluoroquinolone use in german icus with a stable volume of overall antibiotic use .
the latter two antibiotic classes have been repeatedly identified as risk factors for carriage of multidrug resistant gram - negatives .
carbapenems on the other hand are first - line drugs for the treatment of infections due to esbl - producing bacteria .
it is tempting to assume that overuse of fluoroquinolones and 3gc antibiotics contributed to the observed increase in esbl producers , which subsequently increased carbapenem use .
the ecological nature of the data , however , makes it difficult to infer clear cause - and - effect relationships , as does the failure to differentiate between hospital- and community - acquired isolates and clinical versus surveillance cultures .
in addition , the analysis of trends is hampered by variation in the number of participating icus over time .
nevertheless , the increased burden of multidrug - resistant gram - negative bacteria is a real phenomenon .
in contrast to mrsa , esbl producers - notably strains of escherichia coli carrying plasmids of the ctx - m family - are mostly imported from the community into the hospital . assuming a relationship with antibiotic use in animals and subsequent transmission of antibiotic resistant e. coli via the food chain is alluring , but strong epidemiological evidence is still lacking .
the recently started european union - funded saturn project ( impact of specific antibiotic therapies on the prevalence of human host resistant bacteria ) will gather more information on these risk factors . as mentioned above
, antibiotic overuse in humans probably plays a central role in the spread of esbl producers . in the context of this study
it is noteworthy that germany has a relatively high level of fluoroquinolone use in the community . as to antibiotic use in hospitals ,
the overall quantity of antibiotic use in german icus is comparable to that of other countries .
although there is important heterogeneity between icus , inappropriate antibiotic use is still common in germany ( as in many other countries ) , where infectious diseases as a stand - alone speciality and antibiotic stewardship programmes are still underdeveloped . compared to other european countries or highly publicised health threats , such as bioterrorism and swine flu , public awareness and political commitment to control multidrug - resistant microorganisms has been slow to rise in germany . only recently ( 2009 )
has a german reference centre for surveillance of gram - negative bacteria been established , which focuses , among other things , on detection of carbapenemase producing bacteria .
a first outbreak of carbapenemase producing klebsiella pneumoniae in germany has recently been reported , probably linked to an index patient with previous healthcare contact in greece .
the fact that two icus in 2008 reported carbapenem resistant k. pneumoniae in the current study raises the concern that these strains might already be more common in central europe than previously assumed since detection of these strains may be difficult with routine laboratory techniques .
with regard to esbl - producers the growing community reservoir makes it unlikely that we will be able to control the spread by conventional measures targeted at nosocomial infection control .
the promotion of prudent antibiotic use in the community and animal husbandry should therefore be a key priority .
as to carbapenemase - producing enterobacteriaceae , early identification of these strains and aggressive infection control measures seem essential .
examin ing novel decolonization strategies for gram - negative enterobacteriacae might be a further strategy worth evaluating .
if we manage to enforce all these measures , we will hopefully be able to think positive again - even with regard to gram - negatives .
3gc : third generation cephalosporin ; esbl : extended - spectrum betalactamase ; mrsa : methicillin - resistant staphylococcus aureus .
preparation of this commentary was supported in part by the 6th and 7th framework programme of the european community in the context of the projects ' changing behaviour of health care professionals and the general public towards a more prudent use of anti - microbial agents ' ( champ , contract sp5a - ct-2007 - 044317 ) and ' impact of specific antibiotic therapies on the prevalence of human host resistant bacteria ' ( acronym saturn , agreement fp7-health-2009-n241796 ) .

Answer:
the increasing prevalence of multiresistant gram - negative bacteria of the enterobacteriaceae family in europe is a worrisome phenomenon .
 extended spectrum betalactamase - producing escherichia coli strains are widespread in the community and are frequently imported into the hospital .
 of even more concern is the spread of carbapenem - resistant strains of klebsiella spp . from regions where they are already endemic .
 antibiotic use is a main driver of antibiotic resistance , which again increases broad spectrum antibiotic use , resulting in a vicious circle that is difficult to interrupt .
 the present commentary highlights important findings of a surveillance study of antimicrobial use and resistance in german icus over 8 years with a focus on gram - negative resistance .


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:
Enantioselective Synthesis of \xce\xb1-Secondary and \xce\xb1-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation

Paper sections:

Piperazine is a common structural motif in pharmaceuticals and is considered to be a privileged scaffold in medicinal chemistry.[1] Piperazine itself has been used as an anthelmintic and notable piperazine-containing small molecule pharmaceuticals include imatinib (1), a kinase-inhibiting anticancer agent;[2] ciprofloxacin (2), a potent fluoroquinolone antibiotic;[3] piribedil (3), an antiparkinsonian agent;[4] and indinavir (4), an HIV protease inhibitor (Figure 1a).[5] Common methods for the selective asymmetric preparation of substituted piperazines[6] include enantio selective hydrogenation,[7] enzyme-mediated chiral resolution,[8] α-lithiation mediated by (−)-sparteine and other chiral diamines,[9] Pd-catalyzed cyclizations,[10] or synthesis from amino acids or other members of the chiral pool.[11] One of the most straight forward methods for the synthesis of chiral piperazines is the reduction of the corresponding chiral keto- or diketopiperazine. However, methods for the asymmetric preparation of these piperazine precursors are currently limited.

Piperazin-2-ones possess an additional functionality (i.e. the carbonyl) that allow for the synthesis of more highly substituted piperazine-2-ones, which, upon reduction, yield substituted piperazine derivatives. Although piperazin-2-ones are employed infrequently in medicinal chemistry, they can be found in some pharmaceutical agents including the p53/MDM2 inhibitor (−)-nutlin-3 (5, Figure 1a),[12] and in several naturally occurring bioactive compounds including the marcfortines,[13] pseudotheonamides,[14] and malbrancheamides (Figure 1b).[15] Piperazin-2-ones also play a crucial role as conformationally constrained peptidomimetics. These piperazin-2-ones mimic inverse γ-turns in peptides, which play crucial roles in the secondary structures of proteins.[16] Chiral piperazin-2-ones[17] can be prepared from amino acids or other members of the chiral pool[18] or by chiral auxiliary-mediated alkylations[19] or dynamic resolutions.[20] However, most of the available methods are not capable of generating chiral α-tertiary piperazin-2-ones (6, Figure 2) and there are no previous examples that prepare this motif by catalytic enantioselective methods. Thus, there is an unaddressed absence of catalytic asymmetric synthesis strategies to these valuable compounds.

Our research group has had a longstanding interest in the construction of α-tetrasubstituted carbonyl compounds including quaternary centers using transition metal catalysis and has developed conditions for the asymmetric allylic alkylation of lactams to furnish α-quaternary lactam products.[21] Morpholin-3-ones were also identified as viable substrates under the same conditions, generating an α-tertiary stereo center.[22] We sought to extend this catalyst system to enantio selectively generate α-tertiary piperazin-2-ones (6), which, upon subsequent reduction, would generate chiral tertiary piperazines (7). α-Tertiary piperazine species are not well precedented in the literature presumably due to the difficulties associated with their preparation, and no general methods exist for their asymmetric synthesis, let alone catalytic asymmetric synthesis. A direct, catalytic asymmetric synthesis of tertiary piperazin-2-ones and their subsequent reduction to the piperazines would provide access to an invaluable scaffold, enabling the exploration of unprecedented chemical space (Figure 3).

Medicinal chemistry has long utilized linearly substituted, non chiral piperazines and has also, although less frequently, utilized chiral α-secondary piperazines, as in indinavir (4).22 Access to enantiopure α-tertiary piperazines would provide a unique opportunity to explore these three dimensionally elaborated piperazines in drug discovery.

Given that secondary and tertiary nitrogen atoms may exhibit undesired reactivity in Pd-catalyzed reactions, it is necessary to protect both nitrogens of the ketopiperazine ring. Taking into consideration our prior results, in which N-benzoyl protected lactams reacted with high enantioselectivities in the decarboxylative asymmetric allylic alkylation,[21e] we began our studies with the 1,4-bisbenzoylated piperazin-2-one 8a (Table 1). When utilizing Pd2 (pmdba)3 [tris(4,4'-methoxydibenzylideneacetone) dipalladium (0)] at 5 mol % catalyst loading and the (S)-(CF3)3-t-BuPHOX ligand at 12.5 mol % loading in a 0.014 M solution of toluene, the bis-N-benzoylated α-allylated product 9a (Table 1) was formed in high yield but modest ee. It was reasoned that the sp2-hybridized nature of the N(4) position was detrimental to the enantioselectivity of the reaction due to its ability to stabilize the enolate intermediate.[23] Taking into consideration the need for an alkyl protecting group at the N(4) position, we next examined 4-benzylpiperazin-2-one 8b (R1=Bz, R2=Bn, R3=Me, R4=H). Under our standard conditions, the N-benzyl-protected α-allylated compound 9b was obtained in both good yield and ee. Additional N(4)-protecting groups were investigated which allow for the chemoselective deprotection of N(4). The para-methoxybenzyl protecting group, which can be cleaved by acidic or oxidative conditions, would allow for orthogonal deprotection. 4-Methoxybenzylpiperazin-2-one 9c was also obtained in good ee but with slightly lower yield than the 4-benzyl compound 9b. Given the slightly higher yield, the 4-benzyl protecting group was selected for further optimization.

In efforts to increase the ee of the allylic alkylated products, additional protecting groups at the N (1) position were examined. Considering that benzoylated compounds provided the best results in the lactam case,[21e] we examined additional acyl protecting groups (Table 1). The para-fluoro benzoyl and para-methoxybenzoyl compounds 9d and 9e were obtained in nearly identical ee and just slightly lower yields, demonstrating that substantial electronic changes of the N(1)-substituent do not have a strong influence on the reaction efficiency or selectivity. However, the reaction is somewhat sensitive toward ortho substitution at the N(1)-benzoyl group as 9f was obtained in a significantly lower enantiomeric excess compared to 9d and 9e. Additionally, the1-carboxybenzyl ketopiperazine 9g was also prepared in high yield, albeit moderate ee. Given these data, the unsubstituted benzoyl group was selected as the optimal choice of N(1)-protecting group, and the benzyl group was selected as the optimal N(4)-group.

With protecting groups for both nitrogen atoms investigated, the scope of the reaction with regard to the α-substituent was examined. Piperazin-2-ones bearing alkyl (9h, 9i) and benzyl (9j) groups were prepared, as was benzyl ether 9k (Table 1), which provides an additional handle for further functionalization. Additionally, bicyclic product 9n, which is reminiscent of the marcfortine core, was obtained in good yield in the reaction (Table 1). The effect of expanding ring size was also examined. The 1,4-diazepan-2-one 9o was formed with only moderate enantiomeric excess, a result that suggests that the reaction is sensitive to ring size, contrary to the lactam examples.[21e]

Common piperazine pharmacophores include N-arylpiperazines and N-methylpiperazines,24 and we sought to determine if 4-aryl ketopiperazines and 4-methyl ketopiperazines were also competent substrates in this chemistry. The low ee observed in bis-benzoylated compound 9a suggests that an sp2-hybridized N(4) position would prove detrimental to the enantioselectivity of the reaction. Despite this, 4-phenyl compound 9p, with its partial sp2-nature of its aniline nitrogen, could be obtained in good yield and with excellent enantiomeric excess (Table 1). The 4-methylketopiperazine 9q could also be prepared in good yield but with slightly diminished ee.

Contrary to results with the piperdinone substrates, we were delighted to find that even the unsubstituted α-secondary ketopiperazine 11a could be obtained in excellent yield and enantioselectivity (Table 2). Previous attempts to generate trisubstituted stereo centers via our asymmetric allylic alkylation of lactam and ketone substrates were unsuccessful. Such experiments have generally resulted in mixtures of mono-, di-, and unallylated products, and the desired trisubstituted product was formed in poor yield and with only moderate ee. We were delighted to find that in the case at hand, unsubstituted α-secondary ketopiperazine 11a could be obtained with no detectable amounts of di- or unallylated byproducts. It is likely that the low acidity of the α-hydrogen of the monosubstituted piperazin-2-one substrate and product is key to obtaining a high yield of the monoallylated product. Given this exciting result, additional allyl substrates were tested (Table 2). Numerous allyl groups are compatible, including methallyl 11b, chloroallyl 11c, and phenylallyl 11d which were all obtained in fair to excellent yield and high enantioselectivity.

The ketopiperazine products can be converted to the related piperazines in two steps, hydrolysis of the benzoyl group to piperazine-2-one 12 followed by reduction of the amide to piperazine 13 (Scheme 1A). The deprotected N(1) position can be further alkylated to form for instance, di-allyl piperazin-2-one 15 (Scheme 1B). Cross-metathesis can also be performed (Scheme 1C). Additionally, the 4-methoxybenzylgroupcan be selectively cleaved under oxidative conditions to form piperazine-2-one 17 (Scheme 1D).

Finally, we have demonstrated that these tertiary piperazines can successfully be incorporated into known piperazine-containing pharmaceuticals, leading to novel analogs with comparable bioactivities in preliminary testing. Substitution on the piperazine ring has been shown to modulate bioactivity and, in some cases, result in more specific and stronger enzyme binding.[25] We considered imatinib (1), an antiproliferative agent developed for the treatment of several cancers, notably including Philadelphia chromosome-positive chronic myelogenous leukemia (CML),[2] to be an ideal candidate for proof of concept. Imatinib targets the Abl tyrosine kinase domain of the Bcr-Abl fusion protein, and it is known that genetic point mutations can render imatinib ineffective because it is no longer able to bind to the enzyme.[26] The piperazine moiety of the molecule forms two key hydrogen bonds to two amino acid residues, and thus plays a crucial role in binding.[27]

Given that the piperazine is so crucial to the binding of imatinib, we wanted to explore whether highly substituted and congested piperazine analogs would disrupt these interactions. Enantiomerically pure, benzylated analog 18 (Scheme 2) was assessed for its antiproliferative activity against the human K562 CML cell line.

N-substituted analog 18 was found to have significantly less antiproliferative activity than imatinib (1, Table 3) signifying that too much bulk around N(4) might perturb key interactions. We also synthesized two novel des-methyl tertiary piperazine-containing imatinib analogs (Scheme 2). These analogs, (S)-20 and (R)-20, were assayed for their antiproliferative activity and were found to have activities slightly greater than that of N-desmethyl imatinib (CGP 74588) 19, the main bioactive metabolite of imatinib. The (R)-enantiomer is slightly more potent ((R)-20, Table 3). These results point to the potential utility of stereochemically-rich piperazines as important building blocks for medicinal chemistry. Additionally, these novel substructures will likely open up new chemical space around a privileged scaffold in drug discovery.

In summary, we have developed the first catalytic enantioselective synthesis of α-tertiary piperazin-2-ones. These important molecules can be easily converted to novel α-tertiary piperazines. This method utilizes palladium catalysts derived from Pd2(pmdba)3 and electron-deficient PHOX ligands to deliver α-tertiary piperazin-2-ones in good to excellent yields and enantioselectivities. This method also allows for the synthesis of α-secondary piperazin-2-ones in modest to excellent yields and good to excellent enantioselectivities. In addition to being tolerant of a variety of N-substitutions, this reaction is also tolerant of substitution at the stereocenter including fused bicycles such as those found in piperazine-2-one-containing natural products. We have further demonstrated that these chiral piperazin-2-ones can be reduced to the corresponding chiral piperazines, and these chiral α-tertiary piperazines can successfully be incorporated into known piperazine-containing pharmaceuticals. Specifically, these piperazines can be incorporated into the imatinib framework without major perturbation of the drug's antiproliferative activity against the human K562 CML cell line, thus indicating the enormous potential that these novel three-dimensionally elaborated chiral piperazines have in drug discovery.

Answer: The asymmetric Pd-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows for the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogs. The introduction of these chiral tertiary piperazines resulted in imatinib analogs that exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.


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:
ventriculo - peritoneal ( vp ) shunting is the preferred and most successful method for managing congenital hydrocephalus .
abdominal complications include peritonitis , ascites , bowel obstruction , bowel and abdominal wall perforation , and inguinal herniae .
an uncommon but recognized complication is formation of an abdominal pseudocyst , with cerebrospinal fluid ( csf ) collecting and being poorly absorbed or not absorbed across the serosa .
the continuous flow of csf within a confined space leads to increased pressure within the abdominal cavity , reducing forward pressure gradient and , eventually , shunt malfunction .
these pseudocysts have traditionally been treated with surgical shunt externalization , antibiotics , and a second surgical procedure for shunt reinsertion .
exploratory laparotomy with a partial excision pseudocyst and placement of a catheter in a quadrant of abdomen is also an option .
we report a 20-month - old female child with a vp shunt and a gradual distension of abdomen since three months , respiratory distress , and bilious vomiting for two days .
right - sided vp shunt insertion was done on the seventh day of life and meningomyelocele repair on the 15 day of life . at the age of three months
, there was shunt malfunction for which the right - sided vp shunt was removed and a vp shunt was inserted on the left side . at the time of index admission
, she presented with a history of gradual distension of abdomen for 3 months and respiratory distress and bilious vomiting for 2 days .
, there was a large , 15 cm  12 cm , nontender , cystic intraperitoneal lump with a smooth surface and ill - defined margins , occupying almost the entire abdomen ; moreover , fingers could be insinuated between the costal margins and the lump .
x - ray of the abdomen showed vp shunt in the left side of the abdominal cavity having ground glass opacity around the shunt , with the displacement of bowel loops to the periphery of the opacity [ figure 1 ] . abdominal ultrasonography
( usg ) revealed a large multiseptate pseudocyst with the presence of the shunt within .
as the baby had considerable respiratory distress , an ultrasound - guided aspiration of 200 ml of a straw - colored fluid was done .
however the fluid recollected immediately with increasing abdominal distension and the symptoms persisted ; hence , we decided to operate on the child .
x - ray abdomen showing a giant psuedocyst on the left lower abdomen with a shunt in situ we went ahead with two - port laparoscopy ; one 5-mm primary epigastric camera port above the cyst placed under vision and one 5-mm port in the right iliac fossa .
the placement of the second port was difficult , as there was a large csf pseudocyst predominantly on the left side of the abdomen , with multiple adhesions of bowel loops around the pseudocyst .
gentle maneuvering and dissection with the scope itself helped identify a window in the right iliac fossa where the second port could be placed .
a grasper was used to gently free all adhesions of the cyst wall to parietes .
the cyst was incised with a hook cautery and 1,100 ml of the csf fluid was drained .
the incision in the cyst wall was extended carefully so as to avoid injury to the adherent bowel loops , and the cyst was then deroofed .
the shunt was repositioned in the right subdiaphragmatic space over the liver after confirming the patency of shunt with a free flow of the csf .
. on sixmonth follow - up , the child is recovering well and is asymptomatic .
insertion of a vp shunt is the preferred and most successful method for the management of congenital hydrocephalus . in the setting of a vp shunt ,
the time from the last shunt procedure to the development of the abdominal csf pseudocyst ranges from 3 weeks to 5 years .
a chest and abdominal x - ray visualizes the position of the thoracoabdominal part of the vp shunt .
pathi reported that ultrasound and computerized tomography features of the vp shunt floating in the thickened sac wall would allow early recognition of this complication .
these pseudocysts have traditionally been treated with surgical shunt externalization , antibiotics , and a second surgical procedure for shunt reinsertion . moreover , exploratory laparotomy with partial excision and marsupialisation of pseudocyst and placement of catheter in a quadrant of abdomen has been done .
an extensive review revealed increasing use of laparoscopic management of this complication . using the technique of laparoscopy , kim et al . excised a portion of the csf pseudocyst , removed the shunt catheter from the residual cavity , and repositioned it within the peritoneal cavity in a 12-year - old boy .
( 2003 ) found that the laparoscopic management of csf pseudocyst , accomplished through 3-mm to 5-mm ports with the help of delicate laparoscopic instruments , minimizes the risk of a laparotomy , and the formation of intraperitoneal adhesions .
furthermore , laparoscopy allows visual confirmation of the adequate flow of the csf from the end of the catheter after it is repositioned .
however , the greatest advantage of laparoscopy lies in its ability to assess the entire abdominal cavity for the presence of adhesions and undertake adhesiolysis when necessary .
this allows placement of the catheter in the quadrant of the abdomen with the maximum absorptive surface .
martin et al . performed laparoscopy in ventriculoperitoneal shunt revision for pseudocyst in two cases and reported the use of extensive adhesiolysis for decreasing the risk of future adhesive obstruction and extending shunt life and thus , recommended laparoscopy for vp shunt revisions .
performed the laparoscopic drainage of a pseudocyst containing 2 liters of fluid and retrieved the catheter from the peritoneal cavity .
esposito et al . recommended that laparoscopy is a safe procedure in patients with abdominal complications of vp shunts , especially in adhesions and pseudocyst formation . on extensive search and review of literature
, we found that minimally invasive technique is a useful modality for the treatment of this complication .
however , the management of this complication is generally done using three ports ( one camera port and two working ports ) .
we recommend that even giant pseudocysts can be managed by the two - port laparoscopic technique as done in another child with giant csf pseudocyst as well .
to summarize , laparoscopy is a useful modality for the treatment of intra - abdominal complications of vp shunt such as adhesions and pseudocyst .
it is effective , avoids multiple laparotomies , and its attendant complications and future adhesions .
it is feasible to manage this complication by using only the two - port laparoscopic technique .

Answer:
insertion of a ventriculo - peritoneal ( vp ) shunt is the most common operative procedure for the treatment of hydrocephalus in children . of the several causes of shunt malfunction ,
 cerebrospinal fluid ( csf ) pseudocyst is relatively uncommon .
 there are several modalities to treat a csf pseudocyst .
 laparotomy is required , at times , more than once .
 we managed a patient of csf pseudocyst with two - port laparoscopy , by deroofing the psuedocyst and repositioning of the shunt .
 this minimally invasive technique avoids morbidity associated with laparotomy and aids in early recovery .


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:
an infliction in the life expectancy figure of patients with sickle cell disease ( scd ) occurred around the middle of the 1970s ( fig .
this minimal increase in life expectancy coincided with my appointment at thomas jefferson university as the associate director of the newly created adult sickle cell center .
the number of adults at that time was small and the transition from pediatrics to adult programs was at the age of 18 years .
the trickle of patients increased gradually and we were faced with adolescent and young adult african american patients who were in a state of confusion .
stripped from the protective sphere of the pediatric world and the empathy of their pediatric hematologists and the pediatric ancillary staff , they were in a state of fear , anxiety , depression and , worst of all , severe pain .
the fact that most patients were barely educated , many without a high school degree , unemployed , mediocre health coverage , and dysfunctional family structure conferred a logarithmic dimension to the problem .
the arrow indicates the infliction point where life expectancy of patients with sickle cell disease began to increase .
the steady stream of admissions of patients with acute painful vaso - occlusive crises ( vocs ) to the emergency department ( ed ) and hospital were not welcome by most providers , hospital administration , the house and nursing staffs .
there was subtle resentment of the patients that sometimes extended to the hematologists who showed compassion to the patients . soon labels such as drug addicts , drug - seeking behavior , and hospital hopping and frequent flyer emerged .
listening to and believing the patients and keeping detailed records of ed and hospital admissions and the analgesics prescribed , revealed that most patients genuinely do not respond to a certain analgesic or a certain dose . increasing the doses of an analgesic or switching to another drug solved the problem in most patients .
accordingly and with the approval of the institutional review board ( irb ) , i issued an identification wallet - sized , plasticized card that was carried by patients and presented to the provider treating their voc in the ed , hospital or any other medical facility .
information printed on both sides of the card included : 1 ) demographic data and a recent photograph ; 2 ) hematological data including reticulocyte count ; 3 ) medical data including the type of scd , its complications and co - morbidities if present ; 4 ) all medications being taken by the patient and the recommended treatment of vocs including the name , dose , and the route of administration of the analgesics in question ; and 5 ) my name and contact information for answering questions if needed .
it was not expensive to issue these cards . a polaroid camera available at that time and a laminator were the only equipments needed to issue these cards .
later on , information on the card was computerized and a printed copy was given to the patient .
the patients were very compliant in carrying it as faithfully as they carry their medical cards .
some providers liked it very much because it facilitated having a concise history about the patients .
while this controversy was brewing , interesting developments in basic science were in progress to understand the pharmacodynamics and pharmacokinetics of opioids .
in the 1970s , it was hypothesized that opioids have receptors to bind to and activate in order to relieve pain   by blocking or minimizing the transmission of painful stimuli and raising the pain threshold .
it did not take long after that to identify opioids as ligands that bind to stereospecific and saturable receptors in the central nervous system and other tissues [ 3 , 4 ] .
in addition , recent elegant studies [ 6 - 10 ] have revealed a helical structure of the opioid receptors , which forms pockets in which the corresponding opioid ( ligand ) fits snugly ( fig .
recognition is highly specific , such that only l - isomers of certain opioids exert analgesic activity .
physiologically , by binding to receptors , opioids initiate a series of biochemical events including activation of g proteins , inhibition of adenylate cyclase , and extrusion of potassium ions , resulting in hyperpolarization of cell membranes [ 14 - 16 ] ; this delays or prevents transmission of painful stimuli .
thus , the riddle why some patients respond to one opioid but not another had a pathophysiologic explanation .
( a ) morphine - like molecule ( yellow ) in the deep pocket ( blue ) of the -opioid receptor . ( b )
-opioid receptors from an intimate pair when crystallized with a ligand ( yellow ) such as morphine . knowing how an opioid molecule ( yellow ) sticks in the pocket of its receptor ( blue )
parallel to the progress in the pharmacodynamics of opioids mentioned above , a concomitant advance in the pharmacokinetics of opioids was bubbling to the surface .
phase i involves the cyp enzymes and phase ii metabolism conjugates the drug to hydrophilic substances , such as glucuronic acid , sulfate , glycine , or glutathione .
morphine , hydromorphone and oxymorphone are metabolized by glucuronidation , whereas the majority of the other opioids are metabolized by the cytochrome p450 isoenzyme system .
the net effect of an opioid depends on the availability of enzyme(s ) to convert it into metabolites that could be active or inactive .
briefly , the cyp2d6 genotypes are categorized into phenotypes based on the activity of the variant enzymes .
ultrarapid metabolizers ( ums ) have greater than normal activity due to duplication or triplication , of active alleles [ 20 - 23 ] , extensive metabolizers ( ems ) have normal enzyme activity , intermediate metabolizers ( ims ) have decreased enzyme activity , and poor metabolizers ( pms ) have absent or little enzyme activity .
patients who are ums of fentanyl would rapidly convert it into inactive metabolites with minimal or absent analgesic effect requiring increasing the dose of fentanyl .
on the other hand , patients who are pms of fentanyl would experience prompt relief with relatively small doses of fentanyl but higher doses could be toxic due to the accumulation of unmetabolized fentanyl .
the cyp3a4 enzyme metabolizes more than 50% of all drugs ; consequently , opioids metabolized by this enzyme have a high risk of drug - drug interactions .
together , current data on the pharmacodynamics and pharmacokinetics of opioids show great variability of genotypes among patients and extreme variability in individual responses to opioids . determining the pharmacogenetics profile of each patient
facilitates the choice of drugs that would be efficacious for that patient and avoid those drugs associated with harmful drug - drug interaction .
this approach in diagnostics and therapeutics ushers in the dawn of a new field for the management of individual patients based on their unique pharmacogenetics , phenotypic and biomarker characteristics .
this future approach is referred to as personalized medicine or , more recently , precision medicine .
we hope that this methodology would be approved and sponsored by the insurance companies for patients with scd . in the meantime , listening , believing and respecting the patient with sickle cell pain should be maintained for now as the approach to individualized therapy .

Answer:
in the 1970s , sickle cell pain was treated with trial and error approach by increasing or decreasing the dose of an opioid or switching from one analgesic to another .
 this approach was controversial with criticism and doubt about its usefulness . since then , advances in determining the structure of opioid receptors and the role of the cyp450 enzymes in metabolizing opioids revealed that these anatomic and metabolic findings are not the same in all persons , thus explaining the variability in response to opioids among patients .
 thus , the  trial and error approach  has a scientific basis after all .


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:
since the first practical implementation of electrospray ionization ( esi ) with mass spectrometry reported by yamashita and fenn in 1984 , a number of different atmospheric pressure ionization ( api ) techniques have been developed .
many api techniques require extensive sample preparation as well as costly consumables to obtain mass spectra .
one of the most cost effective and widely available media for chemical separation and analysis is paper .
it has been shown that an electro - osmotic flow similar to that of static electrospray can be utilized to interface a triangle of wetted paper to a mass spectrometer ( ms ) ; this form of analysis is called paper spray ( ps ) [ 49 ] .
the use of a chromatographic medium such as paper allows for the analysis of complex mixtures since separations will occur as the analyte is being driven along the paper medium .
separating analytes on a paper medium provides the benefits of reduced probability of ion suppression and rapid analysis .
the paper medium allows for analysis of complex samples such as biological tissue and dried blood spots which are not suitable for traditional infusion techniques due to their complex matrices [ 4 , 7 ] .
one limitation to ps , like many ms techniques that utilize incomplete chromatographic separations is the detector being utilized to perform the analysis .
when dealing with complex samples or unknown samples , there is a need for high - quality data in order to determine what is being analyzed .
fourier transform ion cyclotron resonance ( ft - icr ) mass spectrometers are powerful tools for analysis of complex mixtures due to their unsurpassed capability to obtain broadband high - resolution mass spectra with high mass accuracy . utilizing ps with a fourier transform ion cyclotron resonance ( ft - icr ) mass spectrometer as a detector allows for rapid analysis of both unknowns and/or complex mixtures . in this present work ,
we show the suitability of a 12  tesla ft - icr ms to obtain high - resolution broadband mass spectra utilizing a coffee filter paper spray medium .
high - resolution mass spectra were first obtained for polypropylene glycol ( ppg ) and polyethylene glycol ( peg ) standards to test the source .
second , urine and calf lung surfactant extract ( clse ) were analyzed to test the ps source for analysis of complex mixtures not suitable for direct infusion .
all solvents used were hplc grade obtained from sigma aldrich ( st . louis , mo , usa ) .
ppg was obtained in the form of a tuning standard from applied biosystems ( bedford , ma , usa ) .
peg standard was made by dissolving 1  mg of peg 2000 obtained from sigma aldrich ( st . louis , mo , usa ) in 1  ml of hplc grade water .
coffee filter , wegmans brand ( rochester , ny , usa ) , was cut by hand into an isosceles triangle with dimensions of approximately 5  mm ( base ) by 10  mm ( height ) .

samples for ppg and peg ps analysis were prepared by wetting the coffee filter triangle with 10  l of the standard solutions .
the wet filter paper samples were allowed to dry under ambient conditions before ps analysis was performed .
mass spectra were then obtained by wetting the dried paper triangle with 10  l of 50  :  50 methanol  :  water and using the method described in section 2.5 .
( amherst , ny , usa ) . prior to analysis , the sample was stored in chloroform in the refrigerator .
samples for clse analysis were produced by wetting a coffee paper triangle with 2  l of clse and allowing the sample to dry under ambient conditions before ps analysis was performed .
mass spectra were then obtained by wetting the paper with 10  l of 50  :  50 methanol  :  water using the instrument method described in section 2.5 .
urine samples were collected from two healthy adult males into sterile polypropylene centrifuge tubes ( vwr scientific ) and immediately placed in the freezer .
the samples were collected in accordance with the health sciences institutional review board at the university at buffalo ( hsirb no .
prior to analysis , the samples were thawed to room temperature and 1  ml was pipetted into 2  ml sample vials ( agilent , santa clara , ca , usa ) for use .
ten l was injected directly onto a triangular coffee filter and allowed to dry under ambient conditions .
once dry , the filter paper was attached to the mass spectrometer via a copper clip and rewetted using 50  :  50 methanol  :  water for ps analysis using the instrument method described in section 2.5 .
high - resolution spectra were obtained on a 12 t bruker solarix ft - icr ms ( bruker daltonics inc . ,
the positive potential was obtained by grounding the paper triangle using a copper clip and applying a negative voltage at the inlet to the mass spectrometer ( figure 1 shows an image of the source ) .
mass spectra were obtained at various mass to charge ranges with a pre - ft - icr - trap hexapole accumulation time of 0.400 seconds and an ft - icr trap accumulation time of 0.025 seconds .
all mass spectra were obtained in the positive mode at a spray voltage of 2  kv .
  polymeric standards were utilized to determine the suitability of ps with high - resolution ft - icr ms . in ft - icr ms the resolution of the mass spectra is relative to m / z as well as the number of data points that can be obtained during the detection process .
high - resolution spectra require a time domain signal stable for longer than several hundred milliseconds .
polyethylene glycol and polypropylene glycol produce a broad m / z range of ions ideal for testing the suitability of ps with high - resolution mass spectrometry .
high - resolution mass spectra of peg and ppg are displayed in figures 2 and 3 , respectively .
identifies of the oligomer ion detected and their associated errors is given in tables 1 and 2 , respectively .
signal - to - noise obtained for peg and ppg after tuning spectra was in excess of 100/1 with absolute intensities that varied shot - to - shot by less than 20% .
this allowed ample time for adjustment of the filter paper towards the inlet of the mass spectrometer so as to optimize instrument setup and analysis .
utilizing polymers of known m
 n values ( provided by the manufacturers ; polydispersity not given ) such as peg 2000 and ppg 2000 provides a detection window several hundred m / z wide for broad mass accuracy calibrations for ft - icr ms .
calf lung surfactant extract ( clse ) , which is commercially available in drug form as infasurf , is used to treat respiratory distress syndrome .
clse is obtained by doing a total lipid extraction on the lavage fluid from a slaughtered calf lung [ 11 , 12 ] .
phosphatidylcholine ( pc ) makes 79% of the molar distribution of lipids and consists of a choline head group attached to the phospholipid with varying degrees of unsaturation in the fatty acid chains .
based on the optimized setup determined from previously analyzing the standards , clse was then analyzed .
ps mass spectra of clse are given in figures 4 and 5 , and the identities with associated error provided in table 3 .
due to the complex nature of urine , many small molecules and metabolites were detected at varying intensities using ps with ft - icr .
ps mass spectra , showing numerous lipids and other metabolites obtained from the analyzed urine specimens of two healthy adult male subjects , are shown in figure 6 ; an inset of one of these ps mass spectra is shown in figure 7 while the other is shown in figure 8 .
a few of the metabolites identified in the 27-year - old volunteer using the exact mass capability of ft - icr are provided in table 4 .
metabolites identified in the 44-year - old volunteer using the exact mass capability of ft - icr are given in table 5 .
of note , the 44-year - old volunteer , who was taking prescribed vitamin d supplements , showed indications of the vitamin d metabolite 25-hydroxyvitamin d2 - 25-glucuronide in the urine .
interestingly , both adult male subjects had indications of one or more glucuronides in urine .
this may signal a particularly strong propensity for glucuronides to ionize via the ps ionization mechanism ; this capability of ps should be further explored .
we developed a ps source for bruker ft - icr instrumentation that can be utilized for a broad range of chemical species .
the ps source was tested on a range of samples and determined the source was suitable for both polymer and biological samples .
the ps source provided an api medium for the analysis of complex mixtures while mitigating the possibility of cross contamination due to the disposable nature of coffee filter paper .

Answer:
paper spray ionization is an atmospheric pressure ionization technique that utilizes an offline electro - osmotic flow to generate ions off a paper medium .
 this technique can be performed on a bruker solarix fourier transform ion cyclotron resonance mass spectrometer by modifying the existing nanospray source .
 high - resolution paper spray spectra were obtained for both organic and biological samples to demonstrate the benefit of linking the technique with a high - resolution mass analyzer .
 error values in the range 0.23 to 2.14  ppm were obtained for calf lung surfactant extract with broadband mass resolving power ( m/m50% ) above 60,000 utilizing an external calibration standard .


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:
autologous peripheral blood hematopoietic cell transplantation ( auto - pbhct ) is a well - established therapeutic option for patients with a variety of hematologic malignancies .
mobilization of peripheral blood progenitor cells ( pbpc ) for auto - pbhct can be accomplished by using cytokines , most commonly granulocyte - colony stimulating factor ( g - csf ) , either alone or in combination with chemotherapy ( e.g. , cyclophosphamide , etoposide , cytarabine , etc . ) or plerixafor [ 1 , 2 ] .
recently reported phase iii studies have also shown superiority of the combination of g - csf with plerixafor over g - csf alone for mobilizing pbpc in patients with non - hodgkin lymphoma ( nhl ) and multiple myeloma ( mm ) [ 3 , 4 ] .
plerixafor acts by selective and reversible antagonism of cxcr4 on cd34 + hematopoietic stem cells ( hsc ) .
this results in disruption of its interaction with cxcl12 ( formally sdf1 ) on bone marrow stromal cells , that cause a rapid release of stem and progenitor cells from bone marrow into peripheral blood .
while plerixafor - based pbpc mobilization can circumvent the need for chemotherapy to mobilize cd34 + pbpcs , to our knowledge no prospective trials comparing plerixafor plus g - csf to chemomobilization have been published to date .
limited data on murine models suggest that a combination of plerixafor and chemotherapy may be more effective than the use of plerixafor alone for pbpc mobilization . despite the promising results of plerixafor and g - csf for pbpc mobilization in patients with mm and nhl [ 3 , 4 , 68 ] , the use of chemotherapy and g - csf - based regimens to mobilize pbpc remains standard practice in many transplant centers .
this decision is often influenced by a desire to improve collection yield , reduce mobilization failures especially in patients who are elderly , heavily pre - treated , and have poor bone marrow cellularity , and/or as an attempt to provide disease control [ 911 ] .
limited data are available on the preemptive use of plerixafor salvage in patients failing to collect adequate numbers of pbpc with chemotherapy and g - csf - based mobilization [ 1214 ] , and this topic has been reviewed recently .
herein we report our experience from two north american transplant centers in a series of patients who received plerixafor salvage while failing chemotherapy and g - csf mobilization .
for patients undergoing chemotherapy and g - csf - based mobilization , it is standard operating procedure at both transplant centers to measure peripheral blood cd34 + cell count daily when the patient 's white blood cell ( wbc ) count recovers to 4,000/l or from day + 12 ( after chemotherapy ) onwards ( whichever occurs first ) .
patients destined to fail pbpc chemomobilization were defined as ( i ) those with a peak peripheral blood cd34 + cell count of < 10/l following wbc count recovery ( wbc count of 4,000/l ) after chemotherapy - induced nadir or ( ii ) those who failed to collect at least 1  10 cd34 + cells / kg after two apheresis sessions . in these patients failing chemomobilization , we administrated plerixafor at a dose of 0.24  mg / kg subcutaneously 10 hours prior to apheresis in conjunction with g - csf ( 10  g / kg ) , as a preemptive salvage strategy . all collections were performed with a cobe spectra apheresis system ( caridianbct , lakewood , co ) , by processing three to four blood volumes .
it is the institutional policy at both transplant centers to routinely target collection of 5  10 cd34 + cells / kg .
determination of peripheral blood cd34 + cell count and cd34 + cell content of the apheresis product was performed at the georgia health sciences university hla laboratory and west virginia university hospitals flow cytometry laboratory .
the bd facscanto ii flow cytometer , ( becton dickinson , san jose , ca ) was used for all analyses .
after red blood cell lysis , washed samples were used for cd34 + enumeration with pe - labeled , 8g12 clone , immunoglobulin g1 ( becton dickinson , san jose , ca ) based on international society of hematotherapy and graft engineering ( ishage ) guidelines .
the final products were cryopreserved in 10% dmso using a controlled rate freezer and stored in liquid nitrogen .
successful mobilization was defined as a total of 2  10 cd34 + cells / kg patients body weight in the final product .
data was collected on mobilization and transplant outcomes through an electronic data base , prospectively maintained at each participating institution and analyzed utilizing spss version 13.0 .
patient characteristics and transplantation outcomes of 16 patients who were failing chemomobilization ( as defined above ) and received preemptive plerixafor are summarized in table 1 .
patients had received a median of two lines of therapies ( range 13 ) prior to pbpc mobilization . after recovering from chemotherapy - induced count nadir ( i.e. , wbc  4000/l ) , 15 patients had a peak peripheral blood cd34 + cell count of < 10  l .
five patients underwent at least 2 sessions of apheresis but were unable to collect 1 million cd34 + cells / kg .
these patients subsequently received a median of two doses of plerixafor salvage ( range 18 ) .
the median number of apheresis sessions was 3.5 ( range 27 ) , and the median number of cd34 + cells collected was 3.9  10 cells / kg ( range 2.47.8 ) . utilizing a cutoff of 2  10 cd34 + cells / kg , all patients who received plerixafor had a successful collection .
nineteen percent of the patients were able to collect 5  10 cd34 + cells / kg .
three patients ( one with hodgkin lymphoma and two with nhl ) required more than four doses of plerixafor , but all eventually collected 2  10 cd34 + cells / kg .
the median peak peripheral blood cd34 + cell count prior to plerixafor administration was 3.5/l ( range 015 ) and increased to 6/l ( range 247 ) after the first dose of plerixafor ( p = 0.03 ) .
93% of the patients had a peak peripheral blood cd34 + cell count of < 10/l before plerixafor salvage .
four patients had a peak peripheral blood cd34 + cell count of 1/l before plerixafor salvage .
kinetics of peripheral blood cd34 + cell and wbc count changes after each dose of plerixafor for these 4 patients is shown in table 2 .
after transplantation , the median time to neutrophil and platelet engraftment was 10 days ( range 915 ) and 20 days ( range 929 ) , respectively . in order to identify predictors of response to plerixafor salvage ,
as expected , patients with a higher peripheral blood cd34 + cell count at the time of the first plerixafor dose had a higher magnitude of change in their peripheral blood cd34 + cell counts ( r = 0.58 , p = 0.01 ) .
only three patients had a cd34 + cell count of 10/l before the first dose of plerixafor , and their median increase was 18/l compared to 6/l for patients who had peripheral blood cd34 + cell counts of < 10/l however , this difference was not statistically significant ( p = 0.3 ) .
we did observe a positive correlation between peak peripheral blood cd34 + cell count before the first dose of plerixafor and the total number of cd34 + cells collected at apheresis ( r = 0.62 ; p = 0.01 ) .
of the 41 collections with plerixafor , the mean cd34 + cell dose collected was 0.79  10 cd34 + cells / kg from 25 collections in patients with a peripheral blood cd34 + cell count < 10/l versus 2.09  10 cd34 + cells / kg from 16 collections in patients with a cd34 + cell count greater than 10/l ( p = 0.001 ) .
correlation analyses were performed in order to define an optimal cutoff of wbc count that can be used as a marker for the initiation of plerixafor salvage , which showed that wbc count had no correlation with a change in cd34 + cell count after the first dose of plerixafor ( r = 0.21 , p = 0.41 ) .
utilizing the median wbc count of 32/l at the time of administration of plerixafor in our patients , we found that we were able to collect a higher number of cd34 + cells in patients who had a wbc count 32/l as compared to those with a wbc count > 32/l ( 1.67  10/kg versus 0.8  10/kg , p = 0.02 resp . ) .
our limited multicenter outcomes data suggest that the addition of plerixafor as a preemptive salvage may rescue patients who are destined to fail chemotherapy and g - csf - based pbpc mobilization .
in our series we used plerixafor salvage to rescue an otherwise failed attempt for chemomobilization , which contrasts with prior studies where plerixafor was used to remobilize patients who had failed prior mobilization attempts .
this is also in contrast to studies where plerixafor was routinely given to patients undergoing chemomobilization . in our series plerixafor
was given after recovery from chemotherapy - induced count nadir ( median of 11.5 days after chemotherapy ) and resulted in successful cd34 + cell collection in all patients , who were otherwise likely to fail chemomobilization .
interestingly patients with a wbc count of  32/l were able to collect a higher number of cd34 + cells .
this is in contrast to earlier data [ 1215 ] that indicated limited efficacy of plerixafor in patients with a lower wbc count .
this discrepancy can be a reflection of the decreased efficiency of the collection process in patients with a higher wbc count or possibly a reflection of timing of plerixafor administration .
generally a cd34 + cell count of 1013/l is used as a cutoff for initiating apheresis following cytokine only , cytokine plus plerixafor , or chemomobilization in majority of transplant centers in the country . the median cd34 + cell count of our patients was only 3.5/l with 82% less than 10/l at the time of the first plerixafor dose , and all patients were able to collect a minimum of 2  10 cells / kg . however
, a valid cutoff for peripheral blood cd34 + cell count to initiate apheresis when plerixafor is used as a salvage for failed chemomobilization is unknown .
patient characteristics and institutional preference will likely continue to influence the choice for mobilization strategy in patients undergoing an auto - pbhct . while no prospective data are available to demonstrate better efficacy or cost effectiveness of plerixafor - based mobilization over chemotherapy - based mobilization , our preliminary data provide safety and efficacy data for plerixafor salvage to rescue patients failing chemotherapy - based pbpc mobilization .

Answer:
the combination of filgrastim ( g - csf ) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non - hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation .
 however , chemotherapy and g - csf - based mobilization remains a widely used strategy for peripheral blood progenitor cell collection . in this paper
 we describe our experience from two north american transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and g - csf mobilization .
 patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery .
 the use of plerixafor was associated with a 2.4-fold increase in peripheral blood cd34 + cell count and 3.9-fold increase in total cd34 + cell yield .
 all patients were able to collect 2  106 cd34 +  cells / kg with this approach .
 these results were more pronounced in patients with a higher cd34 + cell count at the time of the first plerixafor dose .
 interestingly , peripheral blood white blood cell count was not shown to correlate with a response to plerixafor .
 our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization .