Fresh frozen plasma and platelet utilization
The authors of this study reported normative rates of expiration and wastage
for units of fresh frozen plasma and platelets. Participants in the CAP Q-Probes
laboratory quality improvement program collected data retrospectively on the
number of units of FFP and PLTs that expired or were wasted due to mishandling.
The participants also completed questionnaires describing their hospitals' and
blood banks' laboratory and transfusion practices. The studies covered 1,639
public and private institutions and included data submitted on 8,981,796 units
of FFP and PLTs. The aggregate combined FFP and PLT expiration rates ranged
from 5.8 to 6.4 percent, and aggregate combined FFP and PLT wastage rates ranged
from 2.0 to 2.5 percent. Among the top-performing participants (at the 90th
percentile and above), FFP and PLT expiration rates were 0.6 percent or lower
and FFP and PLT wastage rates were 0.5 percent or lower. Among the worst-performing
participants (at the 10th percentile and below), expiration rates were 13.8
percent or higher and wastage rates were 6.8 percent or higher. The authors
were unable to associate selected hospital characteristics or blood bank practices
with lower rates of FFP and PLT utilization. They concluded that it is possible
for hospital blood bank personnel to achieve FFP and PLT expiration and wastage
rates of less than one percent.
Novis DA, Renner S, Friedberg RC, et al. Quality indicators
of fresh frozen plasma and platelet utilization. Arch Pathol Lab Med.
Reprints: Dr. David A. Novis, Dept. of Pathology, Wentworth-Douglass Hospital,
Dover, NH 03820; email@example.com
DHEA-S levels and depressive symptoms in perimenopausal women
Relatively little is known about the endocrine changes that occur in women in
the late reproductive and premenopausal years and how these are affected by
racial factors. Young adult women have high levels of the adrenal androgen dehydroepiandrosterone
sulfate (DHEA-S). These levels decrease with age to about 25 percent of peak
levels in the aged, and it has been thought that DHEA-S plays an important role
in the aging process. In studies of predominately Caucasian women or those in
whom race was not specified, low DHEA-S levels in the elderly and declining
levels in midlife have been associated with increased risk of depressive symptoms.
The authors undertook a cross-sectional study using a population-based urban
sample recruited through random-digit telephone dialing. They developed a sample
composed of 338 women aged 35 to 47 with regular menses. Half of these women
were African-American and the other half were Caucasian. Women in the younger
half of this cohort were found to have higher DHEA-S levels, which were associated
with depressive symptoms, whereas in the older half of this cohort, lower DHEA-S
levels were associated with depressive symptoms. The direction of the relationship
of DHEA-S and depressive symptoms changes with age, being a positive relationship
in younger women and an inverse relationship in the older women in this cohort.
The relationships of DHEA-S levels, depressive symptoms, and other hormones
in the hypothalamic-pituitary-adrenal axis need to be better understood in the
premenopausal age group to draw firm conclusions about these results.
Morrison MF, Have TT, Freeman EW, et al. DHEA-S levels
and depressive symptoms in a cohort of African American and Caucasian women
in the late reproductive years. Biol Psychiatry. 2001;50:705-711.
Reprints: Dr. Mary F. Morrison, Merck Research Laboratories, 10 Sentry Park,
Mail Drop BL2-5, Blue Bell, PA 19422
Apoptotic cells in bronchoalveolar lavage
Apoptosis is a mechanism of cell death in healthy tissues and a key regulator
of balance between pro- and anti-inflammatory processes. Apoptosis is down-regulated
by pro-inflammatory mediators, increasing the life span of neutrophils, macrophages,
and other cells. This prolonged survival may cause an unbalanced tissue load
of neutrophils and macrophages and uncontrolled release of toxic metabolites.
Apoptosis has also been shown to be responsible for remodeling various organ
cells during inflammatory response in animals. The mode of lung cell death in
particular patients with severe sepsis is unknown. The authors conducted a study
to determine whether apoptosis is present in bronchoalveolar lavage cells, particularly
alveolar macrophages of septic patients. The authors carried out a prospective
study in the ICU and surgical intensive care and trauma unit of a large university
hospital in Athens, Greece. They obtained BAL specimens from 20 consecutive
patients admitted to two ICUs who met the criteria for sepsis. They also obtained
BAL specimens from nine volunteers without lung disease who served as controls.
Apoptosis was detected using annexin V binding, terminal deoxynucleotidyl transfer-mediated
deoxyuridine 5-triphosphate nick end labeling (TUNEL), DNA laddering, light
microscopy, and immunohistochemistry. The spontaneous apoptosis of BAL cells,
particularly alveolar macrophages, was significantly decreased in septic patients
compared with nonseptic controls. This finding was confirmed using morphologic
criteria and the TUNEL method. Gel electrophoresis of DNA obtained from BAL
cells revealed that DNA fragmentation was not necessarily associated with apoptotic
cell death. An inverse correlation was found between the percentage of apoptotic
alveolar macrophages and the severity of sepsis. The authors concluded that
prolonged survival of lung cells in septic patients, especially alveolar macrophages,
can be attributed to the inhibition of apoptosis. The host in this situation
may be attempting to increase the defense capacity to kill the invading microorganism,
resulting in an unbalanced tissue load of cells and an uncontrolled release
of toxic metabolites downstream. The inhibition of apoptosis in septic patients
also may explain why lung function is impaired, leading to sepsis-induced acute
respiratory distress syndrome and death.
Liacos C, Katsaragakis S, Konstadoulakis MM, et al. Apoptosis
in cells of bronchoalveolar lavage: a cellular reaction in patients who die
with sepsis and respiratory failure. Crit Care Med. 2001;29:2310-2317.
Reprints: Dr. Manousos M. Konstadoulakis, Kalvou 24, P. Psychico, 154 52,
Athens, Greece; firstname.lastname@example.org
Detecting epitestosterone in sports medicine
Epitestosterone is a naturally occurring steroid found in urine in concentrations
similar to those of testosterone. It is produced in the testes and probably
by the ovaries and adrenals, but it has minimal or no androgenic activity. It
is not available as a pharmaceutical agent, but it can be purchased in bulk
from chemical companies. The compound is of great interest in the field of doping
control because it is the denominator in the testosterone/epitestosterone (T/E)
ratio, an indirect marker of testosterone administration. When testosterone
is administered, the excretion rate of urinary testosterone increases, the excretion
rate of epitestosterone declines, and the T/E ratio tends to increase. The increased
T/E ratio is also an indirect marker of androstenedione and dehydroepiandrosterone
administration. If the T/E ratio exceeds six, doping control labs report the
case to the sport authorities, who then investigate. One technique for circumventing
the T/E test is to self-administer epitestosterone. Consequently, the International
Olympic Committee has classified epitestosterone as a urine-manipulating agent
and labs are required to report epitestosterone concentrations of more than
200 µg/L. The authors investigated the carbon isotope ratio of chemical epitestosterones
and determined the δ13C value of urinary epitestosterone
in urine samples obtained from healthy control subjects and athletes. They developed
a gas chromatography-combustion-isotope ratio mass spectrometry method for measuring
the δ13C values for urinary epitestosterone.
Sample preparation involved deconjugation with β-glucuronidase followed
by a solid-phase extraction and semipreparative high-pressure liquid chromatography.
Gas chromatography-mass spectrometry was used to determine epitestosterone concentrations
in urine obtained from a control group of 456 healthy males. The epitestosterone
δ13C values were determined for 43 control urines
with epitestosterone concentrations of 40 µg/L or more and 10 athletes' urines
with epitestosterone concentrations of more than 180 µg/L. The authors found
that the log epitestosterone concentration distribution was gaussian (mean,
3.30; standard deviation, 0.706). The δ13C values
for four synthetic epitestosterones were low and differed significantly. The
standard deviations of between-assay precision studies were low (< 0.73 percent).
The mean δ13C value for urine samples from the
43 healthy males was -23.8 percent. Nine of 10 athletes' urine samples with
epitestosterone concentrations of more than 180 µg/L had δ13C
values within ± 3 standard deviations of the control group. The δ13C
value of epitestosterone in one sample was -32.6 percent, suggesting that epitestosterone
was administered. The authors concluded that determining δ13C
values for urinary epitestosterone may be useful for detecting cases of epitestosterone
administration because the mean δ13C values
for a control group are high compared with the δ13C
values for synthetic epitestosterones.
Aguilera R, Hatton CK, Catlin DH. Detection of epitestosterone
doping by isotope ratio mass spectrometry. Clin Chem. 2002; 48:629-636.
Reprints: Don H. Catlin, UCLA Olympic Analytical Laboratory, 2122 Granville
Ave., Los Angeles, CA 90024; email@example.com
Determining the etiologic agents in sarcoidosis
Medical researchers have known about sarcoidosis for more than 100 years, but
the cause of sarcoid lesions is still unknown. The condition most likely results
from exposure of a genetically susceptible subject to some specific environmental
agent or agents. No specific infectious agent, however, has been identified.
The clinical, histologic, and immunologic similarities between sarcoidosis and
tuberculosis have led some researchers to think that the cause may be an atypical
mycobacterium, but Mycobacterium tuberculosis has never been isolated
in culture from sarcoid lesions. Mycobacterium avium subspecies paratuberculosis
was identified by polymerase chain reaction in cultured isolates in one study.
In Japan, however, Propionibacterium acnes have been isolated in culture
from biopsy samples in 31 of 40 lymph nodes from 40 patients with sarcoidosis.
The authors collected biopsy samples of lymph nodes from patients with sarcoidosis
and tuberculosis and from control samples in two Japanese institutes and three
European institutes. The specimens were obtained from each of the 108 patients
with sarcoidosis and 65 patients with tuberculosis, as well as from 86 control
samples. Quantitative real-time PCR was used to detect genomes of P. acnes,
P. granulosum, M. tuberculosis, M. avium subspecies,
paratuberculosis, and Escherichia coli (as the control). P.
acnes or P. granulosum was found in all but two of the sarcoid
samples from all locations. M. avium subspecies paratuberculosis
was not found in the sarcoid samples. M. tuberculosis was found in
zero to nine percent of the sarcoid samples and 65 to 100 percent of the tuberculosis
samples. There were far more genomes of P. acnes or P. granulosum
in the sarcoid lymph nodes than in the tuberculosis lymph nodes. The authors
concluded that Propionibacterium species are more likely than Mycobacteria
species to be etiologic agents in sarcoidosis, not only in Japanese patients
with sarcoidosis but also in European patients with the condition.
Eishi Y, Suga M, Ishige I, et al. Quantitative analysis
of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European
patients with sarcoidosis. J Clin Microbiol. 2002;40:198-204.
Reprints: Yoshinobu Eishi, Dept. of Human Pathology, School of Medicine,
Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519,
Biomarkers for endometriosis
Endometriosis is an extremely common, benign gynecological condition. There
are, however, no easy ways to diagnose the condition short of laparoscopy. A
considerable amount of evidence implicates disorders of the immune system in
the pathogenesis of endometriosis. Several studies have found that immunological
components of the peritoneal fluid play an essential role in the pathogenesis
and progression of the condition. The peritoneal fluid macrophages and their
cytokine secretory products specifically appear to play an active role. The
authors studied this phenomenon prospectively by analyzing peritoneal fluid
samples from 130 women undergoing laparoscopy for pain, infertility, tubal ligation,
or sterilization reversal. Concentrations of the cytokines (IL)-1β, IL-6,
IL-8, IL-12, IL-13, and TNF-α (tumor necrosis factor alpha) were measured
in serum and peritoneal fluid, and reactive oxygen species were measured in
peritoneal fluid. Fifty-six of the women were diagnosed with endometriosis,
eight with idiopathic infertility; 27 underwent tubal ligation or reanastomosis
(control group); and 39 were excluded because of bloody taps of peritoneal fluid.
Only serum IL-6 and PF TNF-a could be used to discriminate between patients
with and without endometriosis with a high degree of sensitivity and specificity
(P<0.001). Using a threshold cutoff value of 15 pg/mL for PF TNF provided
100 percent sensitivity and 89 percent specificity. A threshold cutoff value
of 2 pg/mL for serum IL-6 provided 90 percent sensitivity and 67 percent specificity.
The authors concluded that these markers may be useful as a nonsurgical diagnostic
tool, but the findings should be verified in a larger study.
Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of
endometriosis with serum and peritoneal fluid markers: a prospective controlled
trial. Hum Reprod. 2001;17:426-431.
Reprints: T. Falcone, Dept. of Obstetrics-Gynecology, The Cleveland Clinic
Foundation, 9500 Euclid Ave., A81, Cleveland, OH 44195; firstname.lastname@example.org
Umbilical cord plasma leptin in preeclampsia
Leptin is the product of the obesity gene. It is expressed primarily in adipocytes
where, through negative feedback loop inhibition between adipose tissue and
the hypothalamus, it may contribute to the regulation of obesity by affecting
satiety mechanisms. Leptin is highly expressed in the placenta in pregnancy.
It has been detected in umbilical cord blood from fetuses at week 18 of gestation,
with increasing levels from the middle of the third trimester toward term. This
increase appears to coincide with the development of fetal adipose tissue. Some
studies indicate that cord blood levels of leptin are positively correlated
with fetal adiposity at birth. Preeclampsia increases fetal risk of being born
small for gestational age, particularly in cases of early and recurrent disease.
Wasting of subcutaneous fat is seen in these growth-retarded infants, thus one
would expect lower levels of leptin in umbilical cord blood from preeclamptic
than from normotensive pregnancies. At least one previous small study, however,
found no difference in cord leptin levels between cases of preeclampsia and
controls with delivery at term. The authors of this study compared umbilical
cord plasma levels of leptin between pregnancies with preeclampsia and normotensive
control pregnancies to assess the relation between fetal adiposity at birth
and leptin levels. On the basis of a population of approximately 13,000 deliveries,
the investigators compared cord plasma leptin from 256 preeclamptic and 607
control pregnancies after taking into account differences in gestational age
and ponderal index. The investigators found that cord plasma leptin levels increased
markedly with gestational age in the preeclamptic group and control subjects.
At each gestational age, however, the preeclamptic group had higher leptin levels
than the control subjects, and this was highly significant (P<.01). The adjustment
for higher ponderal index among the controls did not alter the difference in
leptin levels between the groups. The authors concluded that higher levels of
umbilical cord plasma leptin are found in mothers with preeclampsia than in
Ødegård R, et al. Umbilical cord plasma leptin is increased
in preeclampsia. Am J Obstet Gynecol. 2002;186:427-432.
Reprint information not available.
NMP22 false positives
Urinary tumor markers have not yet proved to be reliable enough to replace cytology
and cystoscopy as the major modalities for diagnosis and followup of bladder
cancer. The NMP22 nuclear matrix protein is a candidate tumor marker in voided
urine. These markers, however, have low specificity and low positive predictive
value due to false-positive results. The false positives tend to occur in the
same clinical categories typically associated with hematuria and pyuria. This
is a serious problem in bladder cancer because 85 percent of patients present
with hematuria. The authors investigated the effect of hematuria and pyuria
on NMP22 results. They examined 202 urine samples from 30 healthy individuals,
20 with symptomatic urinary tract infections, and 32 with known bladder carcinoma.
In the first group, the median urinary NMP22 was 4 U/mL, with a range of 1.6
to 9.5. When blood was added to these urine samples, NMP22 level increased in
parallel to the increase in the amount of red cells in the sediment. When more
than 2 µL/mL of blood was added to the urine of a healthy individual, the NMP22
level was comparable to levels seen in patients with bladder cancer. The leukocyte
count in urine sediment also had a significant impact on the NMP22 levels in
the group with pyuria. Hematuria and pyuria did not significantly affect NMP22
measurements in the group with bladder cancer. The NMP22 clinical parameters
were sensitivity of 78.1 percent, specificity of 66 percent, positive predictive
value of 59.5 percent, and negative predictive value of 82.5 percent. Test sensitivity
increased as grade and stage progressed. The authors concluded that in an experimental
model, pyuria and hematuria significantly affected urinary NMP22 and that the
effect of white blood cells was more pronounced than that of red blood cells.
The source of NMP22 in isolated hematuria remains to be elucidated.
Atsü N, Ekici S, Öge Ö, et al. False-positive results of the NMP22 test due
to hematuria. J Urol. 2002;167:555-558.
Reprint information not available.