Pyridostigmine, a carbamate acetylcholinesterase (AChE) inhibitor, is routinely employed in the treatment of the autoimmune disease myasthenia gravis. Pyridostigmine is also recommended by most Western armies for use as pretreatment under threat of chemical warfare, because of its protective effect against organophosphate poisoning. Because of this drug's quaternary ammonium group, which prevents its penetration through the blood-brain barrier, the symptoms associated with its routine use primarily reflect perturbations in peripheral nervous system functions. Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms. This increase was not due to enhanced absorption (or decreased elimination) of the drug, because the inhibition efficacy of serum butyryl-cholinesterase was not modified. Because previous animal studies have shown stress-induced disruption of the blood-brain barrier, an alternative possibility was that the stress situation associated with war allowed pyridostigmine penetration into the brain. Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose. Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs. Moreover, in vitro exposure to pyridostigmine increased both electrical excitability and c-fos mRNA levels in brain slices, demonstrating that the observed changes could be directly induced by pyridostigmine. These findings suggest that peripherally acting drugs administered under stress may reach the brain and affect centrally controlled functions.
OBJECTIVE:To examine the impact of maternal obesity on the rate of suboptimal ultrasound visualization (SUV) of fetal anatomy and determine the optimal timing of prenatal ultrasound examination for the obese gravida. METHODS: A computerized ultrasound database was used to identify ultrasound examinations for singleton gestations performed between 14 0/7 and 23 6/7 weeks at a tertiary care, university-based hospital. Patients were divided into four groups and categorized based on body mass index (BMI): nonobese (BMI o30 kg/m 2 ), class I obesity (30rBMIo35 kg/m 2 ), class II obesity (35rBMIo40 kg/m 2 ), and extreme obesity (BMI Z40 kg/m 2 ). The rates of SUV for fetal cardiac and craniospinal structures were calculated for each group and compared. RESULTS: A total of 11 019 pregnancies were studied, of which 38.6% of the patients were obese. Overall, the rate of SUV of the fetal structures was higher for obese compared to nonobese women for both cardiac (37. With increasing gestational age at examination, the rate of SUV decreased for both obese and nonobese women. However, for obese women there was minimal improvement in visualization after 18-20 weeks. Even after adjustment for gestational age and the type of ultrasound machine, obese women (class I, class II, and extreme obesity) were still associated with increased odds for SUV of the fetal cardiac and craniospinal structures compared to nonobese women. CONCLUSION: Maternal obesity increases the rate of SUV for the fetal cardiac structures by 49.8% and for the craniospinal structures by 31%. The optimal gestational age for visualization of fetal cardiac and craniospinal anatomy in obese patients may be after 18-20 weeks.
Objective: A sonographically short cervix is a powerful predictor of spontaneous preterm delivery. However, the etiology and optimal management of a patient with a short cervix in the mid-trimester of pregnancy remain uncertain. Microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation are frequently present in patients with spontaneous preterm labor or acute cervical insufficiency. This study was conducted to determine the rate of MIAC and intra-amniotic inflammation in patients with a cervical length -25 mm in the mid-trimester. Study design: A retrospective cohort study was conducted of patients referred to our high risk clinic because of a sonographic short cervix or a history of a previous preterm birth. Amniocenteses were performed for the evaluation of MIAC and for karyotype analysis in patients with a short cervix. Fluid was cultured for aerobic and anaerobic bacteria, as well as genital mycoplasmas. Patients with MIAC were treated with antibiotics selected by their physician. Results: Of 152 patients with a short cervix at 14-24 weeks, 57 had amniotic fluid analysis. The prevalence of MIAC was 9% (5/57). Among these patients, the rate of preterm delivery (-32 weeks) was 40% (2/5). Microorganisms isolated from amniotic fluid included Ureaplasma urealyticum (ns4) and Fusobacterium nucleatum (ns1). Patients with a positive culture for Ureaplasma urealyticum received intravenous Azithromycin. Three patients with Ureaplasma urealyticum had a sterile amniotic fluid culture after treatment, and subsequently delivered at term. The patient with Fusobacterium nucleatum developed clinical chorioamnionitis and was induced. Conclusion: (1) Sub-clinical MIAC was detected in 9% of patients with a sonographically short cervix (-25 mm); and (2) maternal parenteral treatment with antibiotics can eradicate MIAC caused by Ureaplasma urealyticum. This was associated with delivery at term in the three patients whose successful treatment was documented by microbiologic studies.
K E Y W O R D S:amniotic fluid 'sludge'; chorioamnionitis; funisitis; microbial invasion of the amniotic cavity; preterm labor; preterm premature rupture of membranes; short cervix; spontaneous preterm delivery; transvaginal ultrasound
ABSTRACT
Objectives
Repeated ultrasound examination for SUV of the fetal heart at a later gestational age dramatically reduces SUV. However, obese patients continue to have much higher rates of persistent SUV.
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