BACKGROUND: Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.
METHODS: Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.
RESULTS: Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG.
CONCLUSION: Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.
BACKGROUND: Pelvic inflammatory disease (PID) is a common gynecologic disorder. One known complication of PID is tubo-ovarian abscess (TOA) formation. The predominant theory on TOA formation postulates that an ascending infection from the cervix through the uterus to the fallopian tubes and ovaries results in abscess formation. Other theories include seeding via a hematogenous infection, diverticular disease, and appendicitis. CASE: A 39-year-old female patient with abdominal pain was referred to our institution and was found to have a pelvic mass. After a thorough evaluation, surgical exploration revealed the presence of TOA. No evidence of gastrointestinal disease was present. The patient's history was significant for an uncomplicated total abdominal hysterectomy for benign disease of the uterus four years prior. Abscess cultures grew Streptococcus intermedius. CONCLUSION: This case reports the rare occurrence of TOA in a patient who had undergone an abdominal hysterectomy four years prior to presentation. If the patient reports a surgical history of prior hysterectomy, TOA is often stricken from consideration. Although unlikely, adnexal abscess formation should be considered in the differential diagnosis of a patient with abdominal pain and a pelvic mass, even with a remote history of hysterectomy.
Background. Crisscross heart (CCH) is a complex, rare, congenital, rotational, cardiac abnormality that accounts for <0.1% of congenital heart defects (CHD). CCH is characterized by the crossing of the inflow streams of the two ventricles due to an abnormal twisting of the heart. A case of maternal CCH has not been previously reported. Case. We report a case of a primigravida with a CCH, who was separated at birth from her thoracopagus conjoined twin. Pregnancy was managed by congenital cardiology, maternal-fetal medicine, anesthesiology, and obstetrics. She underwent a 39-week vaginal delivery without maternal or neonatal complication. Conclusion. A successful term pregnancy outcome was achieved in a patient with CCH using a multidisciplinary approach to address her cardiac condition.
Objective
To study the interactions of cytoplasmic calcium (Ca2+cyt) elevation, mitochondrial permeability transition pore (mPTP) formation, and reactive oxygen species (ROS) formation in the regulation of phosphatidylserine (PS) exposure in platelets.
Methods and results
mPTP formation, but not the degree of Ca2+cyt elevation, was associated with PS exposure in wild-type, CypD null, ionomycin-treated and ROS-treated platelets. In the absence of the mPTP regulator cyclophilin D agonist-initiated mPTP formation and high-level PS exposure were markedly blunted, but Ca2+cyt transients were unchanged. Mitochondrial calcium (Ca2+mit) transients and ROS, key regulators of mPTP formation, were examined in strongly-stimulated platelets. Increased ROS production occurred in strongly-stimulated platelets and was dependent on extracellular calcium entry, but not the presence of CypD. Ca2+mit increased significantly in strongly-stimulated platelets. Abrogation of Ca2+mit entry either by inhibition of the mitochondrial calcium uniporter or mitochondrial depolarization prevented mPTP formation and exposure, but not platelet aggregation or granule release.
Conclusions
Sustained Ca2+cyt levels are necessary, but not sufficient, for high-level PS exposure in response to agonists. Increased Ca2+mit levels are a key signal initiating mPTP formation and PS exposure. Blockade of Ca2+mit entry allows the specific inhibition of platelet procoagulant activity.
Mesenchymal stemcells (MSCs) have shown a great potential for clinical applications in regenerative medicine. However, it remains challenging to follow the transplanted cell grafts in vivo. Nuclear magnetic resonance spectroscopy (NMR or MRS) is capable of determining and quantifying the cellular metabolites in tissue and organs non-invasively, therefore it is an attractive method for monitoring and evaluating the differentiation and functions of transplanted stem cells in vivo. In this study, metabolic changes of MSCs undergoing adipogenic differentiation to targeted fat cells were investigated in vitro, using solid-state high-resolution magic angle spinning 1H nuclear magnetic resonance spectroscopy. Quantification of metabolite concentrations before and after differentiation of MSCs showed decreased levels of intracellular metabolites, including choline, creatine, glutamate and myo-inositol, and a substantially increased level of fatty acids, when mesenchymal stem cells were differentiated preferentially to fat cells. Intracellular creatine, myo-inositol and choline reduced from 10.4 ± 0.72, 16.2 ± 1.2 and 8.22 ± 0.51 mm to 3.27 ± 0.34, 6.1 ± 0.46 and 3.11 ± 0.32 mm, respectively, while fatty acids increased from 32.6 ± 1.5 to 91.2 ± 3.2 mm after undergoing 3 weeks of differentiation. The increase of the fatty acid concentration measured by NMR is confirmed by the observation of 80% fat cells in differentiated cells by cell counting assay, suggesting resonances from fatty acids may be used as metabolite markers for monitoring MSC differentiation to fat cells in vivo, using the magnetic resonance spectroscopic technique readily available on MRI scanners.
Although the American Academy of Pediatrics recommends breastfeeding for at least 2 years,1 lactating physicians encounter multiple barriers preventing personal attainment of this goal.2,3 Physician leaders recently issued a call to action to support lactating physicians4; but to our knowledge, no studies have systematically examined the current state of lactation-support policies. This study aims to examine lactation-support policies at leading US schools of medicine (SOMs).
Background: Candidal retinitis is a rare but potentially devastating infection in the postoperative patient. Due to the possibility of blindness if the diagnosis and treatment are delayed, we present this report to help educate gynecologic surgeons. Case: A postmenopausal patient presented for the treatment of ovarian carcinoma. Her surgical therapy required radical tumor debulking with partial bowel resection. The patient was begun on intravenous (IV) hyperalimentation through a central venous catheter. On the 7th postoperative day, a cephalosporin antibiotic was administered. Because of persistent fever, a septic workup was instituted and revealed an infected central venous catheter that was culture positive for Candida albicans. The patient complained of visual disturbances and an ophthalmological examination revealed candidal retinitis. Amphotericin B and fluconazole were administered with resolution of her fever and visual changes. Conclusion: The risk factors of malignancy, abdominopelvic surgery, antibiotic therapy, and IV catheters are discussed. In view of the common association of these iatrogenic factors in gynecologic and obstetrical practice, we present this case to help make physicians aware of this potentially devastating infection.
Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 ± 4.2% vs. -29 ± 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 ± 0.15 vs. 1.9 ± 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure.
Objective: To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Design: Randomized controlled trial. Setting: Clinical research center at an academic medical university. Patient(s): Seventeen women with FHA were randomized either to CBT or observation. Intervention(s): CBT versus observation. Main Outcome Measure(s): Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T 3 ), and total and free thyroxine (T 4 ) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Result(s): Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T 3 , or T 4 levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T 3 and T 4 remained unchanged. Conclusion(s): In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA.