bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effect of Diabetes on Proliferation of Vascular Smooth Muscle After Balloon Injury in Rat Aorta
Authors: Dahlfors Gunilla , Chen Yun , Gustafsson Bertil , Arnqvist Hans J.
Published: March 2007

The effect of streptozotocin‐induced diabetes on
cell proliferation in rat aortic intima‐media, as well
as on local gene expression of transforming growth
factor‐β1 (TGF‐β1) was studied. TGF‐β1 mRNA
was measured by solution hybridization and TGF‐β1 protein by ELISA. Proliferation was measured
by bromodeoxyuridine incorporation into DNA two
days after balloon injury. All BrdU‐labelled cells
observed were smooth muscle cells. After a diabetes
duration of 2 and 4 weeks, labelled cells were
significantly fewer compared with controls. Circulating
levels of total TGF‐β1 were lowered in rats
with 2 weeks diabetes. Although the balloon injury
procedure by itself stimulated the gene expression
of TGF‐β1, no significant difference in TGF‐β1
mRNA content between diabetic and control rats
after injury was found. In conclusion: vascular
smooth muscle proliferation in vivo is inhibited by
the diabetic state in this model of insulin deficient
diabetes and this inhibition is not related to an
impaired local expression of TGF‐β1.
The Relationship Between Cholesterol Absorption and Intestinal Cholesterol Synthesis in the Diabetic Rat Model
Authors: Gleeson Aine , Owens Daphne , Collins Patrick , Johnson Alan , Tomkin Gerald H.
Published: March 2007

The chylomicron remnant particle is thought to be particularly atherogenic and we have previously shown alterations in post‐prandial lipoproteins which could contribute to their atherogenicity. Cholesterol metabolism is disturbed in diabetes, yet the effect of diabetes on intestinal cholesterol synthesis and absorption has rarely been investigated. The aim of this study was to examine cholesterol absorption and intestinal synthesis of cholesterol in the streptozotocin diabetic rat. Twelve diabetic rats were paired with 12 control rats. [ 14C]‐Cholesterol emulsion was administered and the lymph duct was canulated. Lymph was collected for 4 h. At sacrifice blood was taken for plasma lipoprotein measurements. Chylomicrons were prepared from the lymph by ultracentrifugation and [ 14C]‐cholesterol content was determined by liquid scintillation counting. Lymph apolipoprotein B48 was isolated by gradient gel electrophoresis, and quantified by densitometric scanning. Serum triglyceride and cholesterol were greatly elevated in diabetic compared to control animals (260 ± 90 and 9.8 ± 8.0 mg/ml vs. 1.0 ± 0.4 and 0.6 ± 0.3 mg/ml, p < 0.0001 respectively). Lymph chylomicron apo B48 was similar in the two groups. Cholesterol absorption was not significantly different in diabetic compared to control rats but cholesterol synthesis was significantly, higher in the diabetic animals (550 ± 352 vs. 322 ± 113 μg/h p < 0.03). There was a positive correlation between apo B48 and cholesterol absorption (r = 0.70, p < 0.01) in the diabetic rats and control rats (r = 0.71, p < 0.01) but no correlation between apo B48 and cholesterol synthesis in either group. This study demonstrates that cholesterol synthesis was increased in diabetes whereas cholesterol absorption was unaffected suggesting that intestinal cholesterol synthesis made an important contribution to the hypercholesterolaemia seen in the diabetic animals.
Alterations in Nitric Oxide Activity and Sensitivity in Early Streptozotocin‐Induced Diabetes Depend on Arteriolar Size
Authors: vanDam Bastiaan , Demirci Cihan , Reitsma Hans J. , van Lambalgen Anton A. , van den Bos Gerard C. , Tangelder Geert Jan , Stehouwer Coen D. A.
Published: March 2007

Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks′ streptozotocin‐diabetic rats (n = 6) and of agematched controls (n = 8), basal inside diameters of A2–A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after NG‐nitro‐L‐arginine. In diabetic rats, cholinergic vasodilatation in A2–A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin‐diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin‐diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin‐induced diabetes. These streptozotocin‐induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree.
Changes in the Growth Hormone‐IGF‐I Axis in Non‐obese Diabetic Mice
Authors: Landau Daniel , Segev Yael , Eshet Rina , Flyvbjerg Allan , Phillip Moshe
Published: March 2007

We investigated the changes in GH‐IGF‐I axis in
non‐obese diabetic (NOD)‐mice, a model of insulin dependent
diabetes mellitus. Diabetic female NOD
mice and their age‐ and sex‐matched controls were
sacrificed at 4, 14, 21 and 30 days (30d DM) after the
onset of glycosuria. Serum GH levels increased and
serum IGF‐I levels decreased in the 30d DM group
(182 ± 32% and 45 ± 24% of age‐matched controls
respectively, p < 0.05). Another group (30d DM + I)
was given SC insulin, and its serum IGF‐I levels
remained decreased. Liver GH receptor (GHR) and
GH binding protein (GHBP) mRNA levels, as well
as liver membrane GH binding assays were deeply
decreased in the 30d DM group in comparison to
controls. GHR message and binding capacity remained
decreased in the 30d DM + I group. Renal
GHR mRNA was decreased at 21d DM but not at
14d DM, whereas GHBP mRNA remained unchanged
throughout the experiment. In conclusion,
increased serum GH levels are documented in NOD
diabetic mice, similarly to the changes described in
humans. The decrease in GHR levels and decreased
serum IGF‐I in spite of increased circulating GH
suggest a state of GH resistance.
Leptin in Children with Newly Diagnosed Type 1 Diabetes: Effect of Insulin Therapy
Authors: McCormick Kenneth L. , Mick Gail J. , Butterfield Lisa , Ross Hugh , Parton Elaine , Totka Joan
Published: March 2007

Leptin, the gene product of adipose tissue that signals
caloric plentitude via central nervous system
receptors, may also have diverse peripheral metabolic
actions. Of paramount interest has been the
potential interaction(s) between leptin and insulin.
Insofar as insulin alters leptin secretion/action (or
vice versa), dysregulation of this system could contribute
to disease states such as diabetes.

The purpose of this study was to examine the
effect of exogenous insulin on serum leptin in
children with newly‐diagnosed Type 1 diabetes.
Since these patients are hypoinsulinemic (insulindeplet.
ed) at diagnosis, they present an ideal
opportunity to examine the effect of insulin repletion
on serum leptin. Seventeen patients were
enrolled. At baseline (prior to insulin therapy),
leptin levels were 4.3 ± 1.1ng/ml; they were not statistically
related to the baseline serum insulin or
illness severity. There was no significant change in
serum leptin before, shortly (1–6 days) or several
weeks (3–26 weeks) after insulin treatment even
when the data was corrected for changes in BMI,
hemoglobin A1C, and daily insulin dose. Since
repletion of the insulin deficiency that is present
in non‐acidotic, ambulatory patients with new
onset Type 1 diabetes did not alter serum leptin,
these results argue against an effect of insulin on
serum leptin in the absence of the acute diabetic
ketoacidosis. Because as the recuperative months
following the diagnosis of new onset Type 1
diabetes are marked by weight gain, the absence
of a rise in serum leptin might also indicate
either an adaptive (weight permissive) or pathologic
(impaired secretory) deficit.
Role of Protein Kinase C, PI3‐kinase and Tyrosine Kinase in Activation of MAP Kinase by Glucoseand Agonists of G‐protein Coupled Receptors in INS‐1 Cells
Authors: Böcker Dietmar , Verspohl Eugen J.
Published: March 2007

MAP (mitogen‐activated protein) kinase (also called
Erk 1/2) plays a crucial role in cell proliferation and
differentiation. Its impact on secretory events is less
well established. The interplay of protein kinase C
(PKC), PI3‐kinase nd cellular tyrosine kinase with
MAP kinase activity using inhibitors and compounds
such as glucose, phorbol 12‐myristate 13‐acetate
(PMA) and agonists of G‐protein coupled receptors
like gastrin releasing peptide (GRP), oxytocin (OT)
and glucose‐dependent insulinotropic peptide (GIP)
was investigated in INS‐1 cells, an insulin secreting
cell line. MAP kinase activity was determined by
using a peptide derived from the EGF receptor as a
MAP kinase substrate and [ 32P]ATP. Glucose as well
as GRP, OT and GIP exhibited a time‐dependent
increase in MAP kinase activity with a maximum at
time point 2.5 min. All further experiments were
performed using 2.5 min incubations. The flavone PD
098059 is known to bind to the inactive forms
of MEK1 (MAPK/ERK‐Kinase) thus preventing activation
by upstream activators. 20 μM PD 098059
(IC50=51 μM) inhibited MAP kinase stimulated by
either glucose, GRP, OT, GIP or PMA. Inhibiton
(“downregulation”) of PKC by a long term (22h) pretreatment
with 1 μM PMA did not influence MAP
kinase activity when augmented by either of the
above mentioned compound. To investigate whether
PI3‐kinase and cellular tyrosine kinase are involved
in G‐protein mediated effects on MAP kinase, inhibitors
were used: 100 nM wortmannin (PI3‐kinase
inhibitor) reduced the effects of GRP, OT and GIP
but not that of PMA; 100 μM genistein (tyrosine
kinase inhibitor) inhibited the stimulatory effect of
either above mentioned compound on MAP kinase
activation. Inhibition of MAP kinase by 20 μM PD
098059 did not influence insulin secretion modulated
by either compound (glucose, GRP, OT or GIP).
[ 3H]Thymidine incorporation, however, was severely
inhibited by PD 098059. Thus MAP kinase is important
for INS‐1 cell proliferation but not for its insulin
secretory response with respect to major initiators
and modulators of insulin release. The data indicate
that MAP kinase is active and under the control
of MAP kinase. PKC is upstream of a genisteinsensitive
tyrosine kinase and probably downstream
of a PI3‐kinase in INS‐1 cells.
Islet Cell Antibodies Represent Autoimmune Response Against Several Antigens
Authors: Månsson Lisa , Törn Carina , Landin-Olsson Mona
Published: March 2007

To study the antigens involved in the islet cell
antibody (ICA) reaction we selected 30 patient
serum samples (ten in each group) positive for ICA
and one other additional autoantibody, such as
glutamic acid decarboxylase antibodies (GADA),
thyrosine phosphatase antibodies (IA‐2A) or insulin
autoantibodies (IAA). The serum samples were
incubated with the specific antigen (GAD65, IA‐2 or
insulin) and the ICA analysis and the corresponding
immunoprecipitation assay were performed before
and after the absorption.

We could then demonstrate that specific autoantibodies
against GAD65 and IA‐2 could be absorbed
with the corresponding antigen, since ten GADA
positive and six IA‐2A samples turned completely
negative. However, the ICA reaction after absorption
with GADA, IA‐2A and insulin was still present,
although at significantly lower levels. The results
strongly indicate that the ICA reaction represents
simultaneous autoimmunity against several other
antigens beside GAD65, IA‐2 and insulin.
Effect of Combination Therapy with a Calcium Channel Blocker and an Angiotensin‐Converting Enzyme Inhibitor on Renal Hypertrophy and Urinary Albumin Excretion in Diabetic Rats
Authors: Nielsen Birgitte , Grønbæk Henning , Østerby Ruth , Flyvbjerg Allan
Published: March 2007

The objective of this study was to compare the effect
of an angiotensin‐converting enzyme (ACE) inhibitor and
a calcium channel blocker on the development of renal
changes in diabetic rats. Diabetes was induced by an intravenous
injection of streptozotocin in normotensive Wistar
rats. Treatment was commenced immediately in 1 set of
rats with 4 treatment arms: nitrendipine (250 mg/kg fodder),
enalapril (35 mg/L drinking water), both treatments
in combination, or placebo. Treatment was continued for 9
weeks. Another set of rats was left with untreated diabetes
for 3 months followed by 7 weeks treatment as above. When
starting treatment right after induction of diabetes, nitrendipine
significantly reduced urinary albumin excretion
(UAE) to the nondiabetic level (P < .05) without reducing
blood pressure (BP), whereas enalapril failed to significantly reduce UAE despite a reduction in BP. Combining the
two treatments showed no further reduction in UAE compared
to monotherapy with nitrendipine, despite a lower
BP. When leaving diabetic rats untreated for 3 months, only
the coadministration of nitrendipine and enalapril showed
a significant reduction in UAE compared to monotherapy
and placebo treatment, but showed no significant effect
on BP.
Role of Neuropoietic Cytokines in Development and Progression of Diabetic Polyneuropathy: From GlucoseMetabolism to Neurodegeneration
Authors: Skundric Dusanka S. , Lisak Robert P.
Published: March 2007

Diabetic neuropathy develops as a result of hyperglycemia‐
induced local metabolic and microvascular
changes in both type I and type II diabetes mellitus. Diabetic
neuropathy shows slower impulse conduction, axonal degeneration,
and impaired regeneration. Diabetic neuropathy
affects peripheral, central, and visceral sensorimotor
and motor nerves, causing improper locomotor and visceral
organ dysfunctions. The pathogenesis of diabetic neuropathy
is complex and involves multiple pathways. Lack
of success in preventing neuropathy, even with successful
treatment of hyperglycemia, suggests the presence of early
mediators between hyperglycemia‐induced metabolic and
enzymatic changes and functional and structural properties
of Schwann cells (SCs) and axons. It is feasible that
once activated, such mediators can act independently of the
initial metabolic stimulus to modulate SC‐axonal communication.
Neuropoietic cytokines, including interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), leukemia inhibitory factor (LIF),
ciliary neurotrophic factor (CNTF), tumor necrosis factor
alpha (TNF‐α), and transforming growth factor beta (TGF‐
β), exhibit pleiotrophic effects on homeostasis of glia and
neurons in central, peripheral, and autonomic nervous system.
These cytokines are produced locally by resident and
infiltrating macrophages, lymphocytes, mast cells, SCs, fibroblasts,
and sensory neurons. Metabolic changes induced
by hyperglycemia lead to dysregulation of cytokine control.
Moreover, their regulatory roles in nerve degeneration and regeneration may potentially be utilized for the prevention
and/or therapy of diabetic neuropathy.
Prevalence and Clinical Significance of Postpartum Endometritis and Wound Infection
Authors: Chaim Walter , Bashiri Asher , Bar-David Juri , Shoham-Vardi Ilana , Mazor Moshe
Published: March 2007

Objective:To correlate clinical variables (gestational age, severe pregnancy-induced hypertension, gestational diabetes mellitus, history of previous cesarean sections, fetal distress, perinatal mortality, postpartum anemia, Apgar score ≤3 at 1 minute and ≤7 at 5 minutes, and instrumental delivery) with postpartum endometritis (PPE) and wound infection.

Methods:Descriptive cross-sectional study of the outcome of 75,947 term and preterm singleton deliveries; vaginally and by cesarean section from 1989–1997.

Results:The prevalence of PPE after vaginal deliveries was 0.17% (120/68,273). Gestational age of less than 37 weeks, severe pregnancy-induced hypertension, fetal distress, instrumental deliveries, neonatal mortality, postpartum anemia, and Apgar scores of <7 after 5 minutes were significantly associated with PPE. Gestational diabetes and an Apgar score of <3 after 1 minute showed similar frequency with and without PPE. The prevalence of PPE after cesarean section was 2.63% (202/7,677). Preterm cesarean sections, history of previous cesarean sections, anemia, and low Apgar scores were seen more frequently with PPE than without. The incidence of cesarean delivery with gestational diabetes mellitus, fetal distress, and perinatal mortality was similar in presence and absence of PPE. The rate of wound infection after cesarean section was 3.97% (318/7,995). Gestational diabetes mellitus, history of previous cesarean deliveries, and low Apgar scores were significantly more frequent with than without wound infection. Gestational age, severe pregnancyinduced hypertension, fetal distress, perinatal mortality, and postpartum anemia were not associated with wound infection.

Conclusions:Awareness of the aforementioned associations may prevent and shorten hospital stay by early diagnosis and appropriate treatment. Infect. Dis. Obstet. Gynecol. 8:77–82; 2000.
Immunotherapy of Gynaecological High-Risk Human Papilloma Virus Infection With Human Leukocyte Ultrafiltrate
Authors: Spitzbart H. , Hoyme U. B.
Published: March 2007

Objective:In this preliminary presentation the outcome of women following systemic treatment of cervical human papilloma virus (HPV) with a leukocyte ultrafiltrate is reported.

Methods:Cervical brush specimens of 819 women with low-grade CIN-1 were evaluated for HPV infection. HPV-positive patients were treated either by cone biopsy because of suspicious eolposeopy or by antibiotics for symptoms of bacterial cervieitis. The remaining women were considered as asymptomatic carriers of HPV and underwent systemic therapy by a human leukocyte ultrafiltrate in a dosage of 5 IE, 6 times in the first 2 weeks, and additionally as a single dose at weeks 4, 6, 8 and 10.

Results:The leukocyte ultrafiltrate was administered to 97 HPV-positive women. In follow-up 88.7% were HPV negative at week 6; the remaining 11 women were tested negative after completion of a second course of therapy.

Conclusions:These preliminary data on the successful treatment of HPV infection by a leukocyte ultrafiltrate are very promising but have to be supported by additional research. Infect. Dis. Obstet. Gynecol. 8:120–123, 2000.
Candida Sepsis Following Transcervical Chorionic Villi Sampling
Authors: Paz Alona , Gonen Roni , Potasman Israel
Published: March 2007

Background: The use of invasive devices and broad spectrum antibiotics has increased the rate of candidal
superinfections.Candida sepsis associated with pregnancy is rare. Candida sepsis following chorionic villi sampling
(CVS) has never been reported.

Case: A 31‐year‐old pregnant woman presented with signs of sepsis one day after undergoing transcervical CVS.
Blood culture and curettage material yielded C. albicans. She was treated with 400 mg of fluconazole daily for
4 weeks and completely recovered.

Conclusion: Candida sepsis should be considered in the differential diagnosis of sepsis following CVS.
Female Genital Warts: Global Trends and Treatments
Authors: Gall Stanley A.
Published: March 2007

The increasing incidence of human papillomavirus (HPV) infection and HPV‐associated conditions such as genital
warts in women is a global concern. Genital warts are a clinical manifestation of HPV types 6 and 11, and are
estimated to affect 1% of sexually active adults aged between 15 and 49. HPV infection is also strongly associated
with cervical cancer, and is prevalent in as many as 99% of cases. The psychological stress of having genital warts is
often greater than the morbidity of the disease, and therefore successful treatment is crucial. Current treatments
are patient‐applied and provider‐administered therapies. Imiquimod 5% cream, a patient‐applied therapy, is an
efficacious treatment with tolerable side‐effects and a low recurrence rate, and has the potential to be an effective
strategy for the management of genital warts.
Relationship of Vaginal Bacteria and Inflammation WithConception and Early Pregnancy Loss Following In-Vitro Fertilization
Authors: Eckert Linda O. , Moore Donald E. , Patton Dorothy L. , Agnew Kathy J. , Eschenbach David A.
Published: March 2007

Objective: The aim of this study was investigate the impact of vaginal flora and vaginal inflammation on
conception and early pregnancy loss following in-vitro fertilization (IVF).

Methods: We enrolled 91 women who were undergoing IVF. At embryo transfer (ET), all of the women had
quantitative vaginal culture, ET catheter‐tip culture, and vaginal Gram stain scored for bacterial vaginosis and
quantitated for polymorphonuclear leukocytes (PMNs). Conception and early pregnancy loss were compared
with culture and Gram stain results. Statistical analyses included the Chi‐square test, Fisher′s exact test and
the Mann–Whitney U‐test.

Results: The overall live birth rate (LBR) was 30% (27/91), and the rate of early pregnancy loss was 34% (14/41). In
women with bacterial vaginosis, intermediate flora and normal flora, the conception rates were 30% (3/10), 39%
(12/31) and 52% (26/50), respectively (p = 0.06 for trend). Early pregnancy loss occurred in 33% (1/3), 42%
(5/12) and 31% (8/26) of women, respectively (p = 0.06, comparing intermediate and normal flora). The vaginal
log concentration of hydrogen peroxide‐producing lactobacilli was 7.3 ± 1.7 in women with a live birth (n = 27)
and 4.9 ± 2.5 in those with early pregnancy loss (n = 14) (p = 0.1).

Conclusions: IVF patients with bacterial vaginosis and with a decreased vaginal log concentration of hydrogen
peroxide‐producing lactobacilli may have decreased conception rates and increased rates of early pregnancy loss.
A larger prospective treatment trial designed to evaluate the impact on IVF outcomes of optimizing the vaginal
flora prior to IVF may be warranted.
Screening and Counseling Practices Reported byObstetrician–Gynecologists for Patients With Hepatitis CVirus Infection
Authors: Boaz Kathy , Fiore Anthony E. , Schrag Stephanie J. , Gonik Bernard , Schulkin Jay
Published: March 2007

Background: Obstetrician—gynecologists are important providers of primary health care to women, and the
hepatitis C virus (HCV) infection screening practices and recommendations provided by obstetrician—gynecologists
for HCV‐infected patients are unknown.

Methods: We surveyed American College of Obstetricians and Gynecologists (ACOG) Fellows, including 413
Fellows who were participating in the Collaborative Ambulatory Research Network (CARN) and 650 randomly
sampled Fellows, about HCV screening and counseling practices.

Results: In total, 74% of CARN members and 44% of non‐CARN members responded. Demographics and
practice structure were similar between the two groups. More than 80% of providers routinely collected drug
use and blood transfusion histories from their patients. Of the respondents, 49% always screened for HCV
infection when patients had a history of injection drug use, and 35% screened all patientswho had received a blood
transfusion before 1992. For HCV‐infected patients, 47% of the physicians always advised against breastfeeding,
70% recommended condom use with a long‐term steady partner, and 64% advised against alcohol consumption.
Respondents who considered themselves to be primary care providers were no more likely to screen or provide
appropriate counseling messages than were other providers.

Conclusions: Most obstetrician—gynecologists are routinely collecting information that can be used to assess HCV
infection risk, but HCV screening practices and counseling that are provided for those with HCV infection are not
always consistent with current Centers for Disease Control and Prevention and ACOG recommendations.
Cefotetan Susceptibility Testing Against AnaerobicBacteria From Obstetrical and Gynecologic Sources:Comparison of Five Different Methods
Authors: Maccato Maurizio , Riddle Gerald , Faro Sebastian
Published: March 2007

Five different antibiotic susceptibility methods were utilized to test the effectiveness of cefotetan
against 200 anaerobic bacteria recovered from patients with obstetrical or gynecological infections.
The object of this study was to determine if a more economical and rapid method for anaerobic
susceptibility testing was as acceptable as the reference agar dilution method. The five methods
were: 1) broth disk elution, 2) microbroth technique, 3) a commercially available microbroth technique,
4) a commercially available spiral gradient technique, and 5) reference agar dilution. The
minimal inhibitory concentrations (MICs) calculated from the spiral gradient technique were equal
to or within one doubling dilution of the reference system in 99.5% of cases, while the percentage for
the commercially available microbroth system was 96.8%, very similar to the microbroth technique
used in our laboratory that yielded a percentage of 96.3. The disk elution method correlated to the
reference agar dilution method in 95.3% cases. While the overall agreement between these techniques
is good, especially for the spiral gradient system, clustering of certain organisms near the
breakpoint of the antibiotic tested results in variability in the labeling of these organisms as susceptible
or resistant. This problem appears to be particularly significant for the disk elution method.
Therefore, further refinements in these methods of suscleptibility testing are needed in order to
provide a more clinically useful assessment of the susceptibility or resistance of certain bacterial
isolates.
Infection and Infertility
Authors: Faro Sebastian
Published: March 2007

Asymptomatic infection appears to be a common cause of fallopian tube damage resulting in ectopic pregnancy or infertility.
Development of a High Performance LiquidChromatographic Assay Measuring Mezlocillin inSerum or Tissue
Authors: Mya Sandra , Gain Ron E. , Larsen Bryan
Published: March 2007

Objective: This study evaluated the blood and uterine tissue concentration of mezlocillin, a broadspectrum
penicillin.

Methods: We adapted a liquid chromatographic method to measure mezlocillin in serum and
tissue. Mezlocillin reference standard was diluted in water, chromatographed on a reversed phase
C18 column eluted at 1.5 ml/min with acetonitrile and phosphate buffer (1:3 v:v), and detected
spectrophotometrically at 210 nm. Mezlocillin was administered to 14 premenopausal women scheduled
to undergo vaginal hysterectomy. Each patient received a 4 g IV infusion of the drug 30 to 60
min prior to surgery. During surgery, tissue was removed from the uterine cervix and blood was
obtained for assay of mezlocillin content.

Results: Chromatography of the mezlocillin standard furnished a discrete peak with a retention
time of 2.4 min. The sensitivity of the assay was 0.1 µg/ml with a linear response up to 100 µg/ml.
The correlation coefficient for the standard curve was 0.9997. When reference standard was diluted
in pooled human serum, the assay was complicated by interfering compounds. These were removed
by ether extraction. The sensitivity of the assay performed in serum was 3 µg/ml. Serum samples
contained from 81.2 to 358 µg of mezlocillin/ml with an average serum concentration of 207.5 µg/ml.
When serum containing a known amount of mezlocillin was homogenized for a period of time
similar to that required to homogenize tissue samples, a deteatable loss of drug was observed and
was applied as a correction factor to the measured tisulevels. After correction, the average tissue
level was 117.2 µg/ml and ranged from 27% to 98% of the serum levels.

Conclusions: The serum concentration of mezlocillin after IV infusion of 4 g was greater than that
required to inhibit the majority of the most significant organisms responsible for post‐hysterectomy
sepsis. Although tissue levels appeared to be consistently lower than serum levels, they could be
expected to provide an inhibitory effect against many of the bacterial strains that contaminate the
surgical site.
Vaginal Flora in Postmenopausal Women: The Effect of Estrogen Replacement
Authors: Ginkel Paul D. , Soper David E. , Bump Richard C. , Dalton Harry P.
Published: March 2007

Objective:To determine the effect of estrogen replacement therapy (ERT)
on the vaginal flora of postmenopausal women.

Methods: Vaginal cultures were obtained from 15 postmenopausal women
whose hormonal statuses were documented by serum follicle‐stimulating hormone (FSH) and
serum estrogen levels. After 8 weeks of ERT, consisting of 0.1 mg of estradiol delivered daily by
dermal patch, the vaginal cultures were repeated, as were measurements of the vaginal pH,
serum FSH, and serum estrogen levels.

Results: Vaginal cultures revealed no significant change in the incidence
of lactobacilli or of all aerobes. However, the incidence of anaerobic species fell after treatment
from 47% to 13% (P = 0.05), and the incidence of anaerobic gram‐negative rods declined after
treatment from 40% prior to ERT to 7% (P = 0.035). Prior to ERT, the difference in mean
vaginal pH between lactobacilli‐positive and lactobacilli‐negative subjects was not significant,
but, following the administration of exogenous estrogen, the lactobacilli‐positive subjects
exhibited a significantly lower mean vaginal pH (4.4 ± 0.4) relative to the lactobacilli‐negative
population (5.2 ± 0.3) (P = 0.02).

Conclusions: We conclude that women on ERT are less likely to have vaginal
colonization with anaerobic bacteria when compared with women not using replacement therapy.
Estrogen replacement may potentiate the effect of lactobacilli on vaginal pH.
Placental Transport of Zidovudine in the Rhesus Monkey
Authors: Ridgway Louis E. , King Thomas S. , Henderson George I. , Schenker Steven , Schenken Robert S.
Published: March 2007

Objective: This study was undertaken to characterize the
pharmacokinetics of zidovudine (ZDV) and ZDV‐glucuronide (ZDVG) in the material and:fetal circulations of the rhesus monkey.
Methods: Cannulas were placed in the maternal external jugular and
the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation.
ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as
single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood ,
samples were collected every 20 min for the first 2 h and then every hour for the next 4 h.
Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance
liquid chromatography (HPLC) with ultraviolet (UV) detection.
Results: In monkeys who received ZDV, the terminal half‐life (T1/2)
for ZDV was 37±15 and
33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal
ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak
levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean
fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a
maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively.
In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments
was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment
at 60 min post‐injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to
4.2 ± 4.2 at 180 min post‐injection.
Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross
the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some
metabolism of ZDV to ZDVG occurs in the fetal compartment.
Comparison of Five Methods for the Determination of Rubella Immunity
Authors: Sautter Robert L. , Crist Arthur E. , Johnson Lynn M. , LeBar William D.
Published: March 2007

Objective: The purpose of this study was to compare the accuracy
of commonly used methods for the detection of rubella immunity, especially the fully
automated IMx assay.

Methods: A total of 190 sera (101 immune and 89 non‐immune)
submitted to Harrisburg Hospital or Polyclinic Medical Center for the determination of
rubella immunity were tested by enzyme immunoassay (IMx and Rubazyme, Abbott
Diagnostic Laboratories, North Chicago, IL), indirect immunofluorescence (FIAX, Whittaker
Bioproducts, Walkersville, MD), and latex agglutination (Rubascan, Becton Dickinson
Microbiology Systems, Cockeysville, MD, and Rubalex, Wellcome Diagnostics, Research
Triangle Park, NC). Specimens were frozen at –30℃ until the study was initiated. Each of
the assays was performed according to the manufacturers′ specifications. Sensitivity,
specificity, accuracy, and positive and negative predictive values for each assay were
calculated using a consensus result of the 5 methods tested.

Results: The sensitivity, specificity, and accuracy, respectively, of the
test systems were as follows: IMx, 96%, 97%, and 96%; Rubazyme, 100%, 99%, and 99%;
Rubascan, 100%, 98%, and 99%; Rubalex, 99%, 97%, and 98%; and FIAX 90%, 100%, and
95%. False negative reactions were seen with the FIAX system.

Conclusions: The IMx system, a new “walk away” system from Abbott
Diagnostic Laboratories and the Rubazyme systems performed well; however the latex
agglutination tests proved to be the most rapid and convenient methods for screening
sera for the presence of rubella immunity.
In Vitro Effect of Local Anesthetics on Candida albicans Germ Tube Formation
Authors: Rodrigues Acácio , Vaz Cidália Pina , Fonseca A. Freitas , de Oliveira J. Martinez , Barros Henrique
Published: March 2007

Objective: This study was planned to clarify the in vitro effect of
lidocaine and bupivacaine on germ tube formation by Candida albicans isolates from
cases of clinical vaginal candidiasis.

Methods: Fourteen C. albicans strains (clinical vaginal isolates)
were grown on Sabouraud agar for 24 h at 37℃ and tested as follows: 100 μl of a yeast
suspension [105
colony forming units (CFU)/ml of phosphate buffered saline (PBS)] was
added to 500 μl of fresh human serum with lidocaine or bupivacaine (pure salts) in serial
concentrations. The test was run in duplicate. Controls were prepared for each strain.
After 4 h of incubation at 37℃, samples were taken from each vial and 200 yeasts were
counted in a counting chamber. The pH of each suspension was measured.

Results: The results are given as the mean of the 2 readings and are
expressed as the percentage of blastoconidia with germ tubes/total blastoconidia.

Conclusions: Our experiments show that both lidocaine and
bupivacaine have a dose‐dependent inhibitory effect, pH‐independent, on germ tube
formation by C. albicans and that both drugs seem to be promising in the treatment of
genital candidiasis due to the combination of anesthetic and antifungal properties.
Septic Shock and Sepsis Syndrome in Obstetric Patients
Authors: Pryde Peter G. , Gonik Bernard
Published: March 2007

Septic shock is a life‐threatening clinical syndrome that, despite its rare occurrence in obstetrics,
remains a leading cause of maternal mortality. Its pathophysiology is explained by a profound
systemic response to a complex variety of host cellular and humoral mediators elaborated after
exposure to microbial toxins. Early recognition, prompt diagnostic workup, and immediate initiation
of therapy improve outcomes. Therefore, recent publications have popularized the concept of the
“sepsis syndrome,” a preshock list of clinical criteria associated with progressive sepsis. Needed
diagnostic studies should never be withheld because of “pregnancy concerns.” With critically ill
patients, the risk‐to‐benefit ratio supports the use of these diagnostic studies in almost all circumstances.
Standard therapy is directed principally at restoring tissue perfusion by intravascular
volume expansion and in some instances vasoactive pharmacological intervention. Simultaneously,
identification of the source of infection and commencement of appropriate empiric antibiotic treatment
are critical. In some cases, surgical abscess drainage or debridement of infected necrotic tissue
will need to be considered. Novel approaches to treatment that attempt to reduce the systemic
response to microbial toxins are promising and under active investigation. Pregnancy‐specific considerations
include the following: 1) initial signs or symptoms of septic shock may be masked by
normal physiologic alterations of pregnancy; 2) a mixed polymicrobial group of organisms, consistent
with lower genital tract flora, should be anticipated; and 3) initial therapy should be directed
at maternal concerns since adverse fetal effects are most likely the result of maternal decompensation.
Incidence of Chorioamnionitis in Patients With Meconium‐stained Amniotic Fluid
Authors: Chapman Shelley , Duff Patrick
Published: March 2007

Objective: The goal of this study was to determine if meconium staining of the amniotic fluid
(MSAF) is a marker for chorioamnionitis.

Methods: In a retrospective, case‐control investigation, we studied 100 patients with MSAF. Each
patient was matched with a control who delivered during the same period but did not have MSAF.
Subjects and controls were matched for age, parity, gestational age, mode of delivery, duration of
rupture of membranes (ROM), length of internal monitoring, and number of examinations before
and after ROM. The incidence of chorioamnionitis in controls and study patients was compared.
The diagnosis of chorioamnionitis was based on clinical examination.

Results: Thirteen of the 200 patients [6.5%, 95% confidence interval (CI), 2.5–10.5%] developed
chorioamnionitis. Of the 100 women with MSAF, 10 (10%, 95% CI, 4–16) were infected compared
with only 3 controls (3%, 95% CI, 0–6, P = 0.04). The odds ratio (OR) for this comparison was 3.3,
and the 95% CI was 1.02–10.63.

Conclusions: MSAF is associated with an increased frequency of chorioamnionitis. Several factors
could explain this association. Infection may cause fetal stress, leading to the release of meconium.
MSAF may enhance the growth of bacteria by providing a rich medium of essential nutrients
or growth stimulants. MSAF also may impair the host immune system so that chemotaxis or
phagocytosis is diminished, thus allowing accelerated growth of microorganisms.
Prophylactic Antibiotics for Suction Curettage in Incomplete Abortion
Authors: Ramin Kirk D. , Ramin Susan M. , Hemsell Patricia G. , Nobles Brenda J. , Heard Molly C. , Johnson Vivian B. , Hemsell David L.
Published: March 2007

Objective: The purpose of this study was to investigate the efficacy of 200 mg of prophylactic
doxycycline in preventing pelvic infection after curettage for spontaneous (incomplete) abortion.

Methods: A randomized, prospective, double‐blinded study was carried out involving 300 women
with an incomplete abortion who were given either placebo or 200 mg of doxycycline orally 30–60
min prior to curettage. A hematocrit, WBC count, pregnancy test, syphilis serology, Neisseria
gonorrhoeae culture, and Micro Trak (monoclonal antibody test, Syba, San Jose, CA) for Chlamydia
trachomatis were performed. The patients were scheduled for follow‐up 2 weeks later. Antibiotic
administration for any reason as well as the postoperative infection rate in these women was
assessed.

Results: Eleven women were excluded from analysis, leaving 289 evaluable. N. gonorrhoeae was
isolated from 6 (2%) women and C. trachomatis from 8 (3%) women, and the syphilis serology was
serofast in 4 (1%) women. Endometritis complicated the procedure in 4 women who received
placebo and in 1 woman who received doxycycline (P = 0.22).

Conclusion: Prophylactic doxycycline is not effective in preventing pelvic infection after curettage
for spontaneous (incomplete) abortion.
Enterobiasis of the Ovary in a Patient With Cervical Carcinoma In Situ
Authors: McCabe Kevin , Nahn Patricia A. K. , Sahin Aysegul A. , Mitchell Michele Follen
Published: March 2007

Background: Enterobiasis occurs throughout the female genital tract and may involve peritoneal
surfaces. It is generally an incidental finding at surgery or at autopsy but occasionally is symptomatic.
Most of the superficial lesions are composed of granulomas with variable fibrosis in which
diagnostic eggs are found, often associated with degenerated adult worms. Multiple histologic sections
may be required to establish the diagnosis in older lesions.

Case: A case of enterobiasis of the ovary in a patient with squamous‐cell carcinoma in situ of the
cervix is presented. The features of enterobiasis are discussed.

Conclusion: The importance of mistaking such lesions for ovarian cancer is discussed.
Bacterial Vaginosis and Trichomoniasis: Epidemiology and Management of Recurrent Disease
Authors: Soper David E.
Published: March 2007

Effective therapies exist for the treatment of both vaginal trichomoniasis and bacterial vaginosis
(BV). Recurrent trichomonas infection is uncommon, and significant metronidazole resistance
remains rare. The management of metronidazole‐resistant trichomoniasis is dependent on susceptibility
studies, which can be used to guide higher doses of metronidazole therapy. Recurrent BV is
common. A mechanism for reestablishing the normal vaginal flora with H2O2‐producing lactobacilli
remains elusive. The management of this recurrent infection is based upon a longer duration of
therapy with currently available antibiotic regimens and documentation of a clinical response using
composite clinical criteria and Gram′s stain of the vaginal secretions.
Epidemiology and Clinical Outcome of Patients Hospitalized With Pelvic Inflammatory DiseaseComplicated by Tubo‐Ovarian Abscess
Authors: Chan Ying , Parchment Winsome , Skurnick Joan H. , Goldsmith Laura , Apuzzio Joseph J.
Published: March 2007

Objective: The purpose of this retrospective study was to compare the clinical outcome and characteristics of pelvic inflammatory disease (PID) complicated by tubo‐ovarian abscess (TOA) with PID
without TOA.

Methods: Chart reviews were performed for all PID admissions to the University of Medicine and Dentistry of New Jersey‐University Hospital, Newark, NJ, from January 1, 1992, to December 31, 1993.

Results: The incidence in this study of TOA based on sonographic evidence of a complex adnexal mass was 18%. The major differences between the patients with and without TOAs were 1) history of hospitalization for PID: 68% (13/19) vs. 29% (25/85); 2) increased erythrocyte sedimentation rate: 82 vs. 41 mm/h; 3) increased WBC count on admission: 16,200 vs. 14,700/ml; 4) failure to respond to initial antibiotic therapy; and 5) longer hospital stay: 7.8 vs. 4.4 days, respectively. Surgical intervention was required in 3 patients: 2 patients who had TOAs and 1 patient who did not have a TOA by clinical examination or by ultrasound.

Conclusions: Despite longer hospital stays and blood tests suggesting more severe disease processes, PID complicated by TOA is usually responsive to intravenous (IV) antibiotic therapy without the need for surgical intervention.
Amniotic‐fluid Lactoferrin: A Marker for Subclinical Intraamniotic Infection Prior to 32 Weeks Gestation
Authors: Heller Kimberly A. , Greig Phillip C. , Heine R. Phillip
Published: March 2007

Objective: Lactoferrin is a glycoprotein released from the secondary granules of activated neutrophils in the setting of infection. The purpose of this study was to determine if amniotic‐fluid (AF) lactoferrin levels are elevated in preterm labor (PTL) patients with subclinical intraamniotic infection (IAI).

Methods: AF samples were obtained from 186 pregnant patients with
the following characteristics: group 1 ‐ term, no labor; group 2 ‐ preterm, no labor; group 3 ‐ PTL with IAI; group 4 ‐ PTL without IAI. Lactoferrin levels were measured with an enzyme‐linked immunosorbent assay (ELISA).

Results: AF lactoferrin levels were elevated in normal gestation after 31 weeks (P < 0.0001). Lactoferrin levels were also higher in infected PTL patients compared with noninfected PTL patients at gestations ≤31 weeks (P = 0.005). An AF lactoferrin level of >2.5 μg/ml is highly suggestive of infection in PTL patients at <32 weeks, with an overall sensitivity of 82% and a specificity of 83%, when infection is defined as a positive AF culture or positive placental histology.

Conclusions: AF lactoferrin levels increase after 31 weeks in normal gestations, but lactoferrin levels >2.5 μg/ml in PTL patients before this gestational age are highly suggestive of IAI. AF lactoferrin levels may be a useful clinical tool for selecting those PTL patients who might benefit from antimicrobial therapy, closer observation, or early delivery.
Tuberculosis in Pregnancy
Authors: Gaither Kecia , Apuzzio Joseph J.
Published: March 2007

Tuberculosis (TB) during pregnancy and in the perinatal period was once considered to be an
infrequent event in the United States. After a decade of steady decline, however, the disease has
begun a resurgence. According to the CDC, a 20% increase in the number of reported cases
occurred between 1985 and 1992. The factors associated with this increase are the emergence of
human immunodeficiency virus (HIV) infection, the development of drug‐resistant organisms,
substance abuse, homelessness, and immigration. Environmental factors promoting transmission
can be found in overcrowded areas such as correctional facilities, nursing homes, hospitals, and
migrant‐worker camps. For a large number of medically underserved women, the obstetrician is
the only interface with medical care, as most of these patients do not have primary‐care providers.
It is important, therefore, that health‐care providers recognize the clinical symptoms of TB and
follow the recognized guidelines for antenatal screening for TB because the omission of these steps
can lead to potentially disastrous sequelae in the fetus and neonate.
Immune Regulation in the Male Genital Tract
Authors: Witkin Steven S. , Jeremias Jan , Bongiovanni Ann Marie , Munoz M. Gladys
Published: March 2007

Spermatozoa are not produced until puberty, long after the establishment of tolerance to self-antigens. Therefore, sperm-specific antigens are immunogenic in men. Most men, however, do not produce antibodies to their own gametes. Development of mechanisms to prevent or limit autoimmune responses to spermatozoa were essential for preservation of reproductive capacity. Tight junctions between adjacent Sertoli cells, as part of the blood-testis barrier, prevent sperm-immune cell contact. In some portions of the genital tract this barrier is thin or incomplete. Immune mechanisms have evolved to actively suppress the autoimmune response to spermatozoa within the genital tract. Unlike in the circulation whereCD4+helper T lymphocytes predominate,CD8+suppressor/cytotoxic T lymphocytes are the most prominant T cells in the epididymis and vas deferens. In addition, spermatozoa suppress pro-inflammatory lymphocyte immune responses, possibly by inducing production of anti-inflammatory cytokines. Antisperm antibody production is induced in the male genital tract when a local infection or disruption in the genital tract physical barrier leads to an influx ofCD4+T cells. In response to induction of a productive immune response, two additional mechanisms downregulate humoral immunity within the genital tract. T lymphocytes possessing the γσ form of the antigen receptor (γσ T cells) are concentrated in the male genital tract and in semen. These cells become activated and proliferate in men with evidence of sperm autoimmunity. Activated γσ T cells inhibit production of antibodies by activated B lymphocytes, thereby limiting antisperm antibody production. Heat shock proteins (hsps) are also present in semen in association with infection and antisperm antibody formation. Hsp gene transcription leads to inhibition of transcription of the genes coding for pro-inflammatory cytokines and, conversely, to activation of γσ T cells. Activated γσ T cells also promote hsp synthesis. The mechanisms to inhibit immunity to sperm may hinder effective immune elimination of microoganisms in the male genital tract.