Dynamic changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth

Glycosaminoglycans (GAG) have diverse functions that regulate macromolecular assembly in the extracellular matrix. During pregnancy, the rigid cervix transforms to a pliable structure to allow birth. Quantitative assessment of cervical GAG is a prerequisite to identify GAG functions in term and preterm birth. In the current study, total GAG levels increased at term, yet the abundance, chain length, and sulfation levels of sulfated GAG remained constant. The increase in total GAG resulted exclusively from an increase in hyaluronan (HA). HA can form large structures that promote increased viscosity, hydration, and matrix disorganization as well as small structures that have roles in inflammation. HA levels increased from 19% of total GAG in early pregnancy to 71% at term. Activity of the HA-metabolizing enzyme, hyaluronidase, increased in labor, resulting in metabolism of large to small HA. Similar to mice, HA transitions from high to low molecular weight in term human cervix. Mouse preterm models were also characterized by an increase in HA resulting from differential expression of the HA synthase (Has) genes, with increased Has1 in preterm in contrast to Has2 induction at term. The Has2 gene but not Has1 is regulated in part by estrogen. These studies identify a shift in sulfated GAG dominance in the early pregnant cervix to HA dominance in term and preterm ripening. Increased HA synthesis along with hyaluronidase-induced changes in HA size in mice and women suggest diverse contributions of HA to macromolecular changes in the extracellular matrix, resulting in loss of tensile strength during parturition.     

A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy

We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.     

Cannabinoids and atherosclerotic coronary heart disease

Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis.     

Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation

Alcohol and vagal activity may be important triggers for paroxysmal atrial fibrillation (PAF), but it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies. We compared self-reported frequency of these triggers in patients with PAF to those with other supraventricular tachycardias (SVTs). Consecutive consenting patients presenting for electrophysiology procedures at a single university medical center underwent a structured interview regarding arrhythmia triggers. Two hundred twenty-three patients with a documented arrhythmia (133 with PAF and 90 with SVT) completed the survey. After multivariable adjustment, patients with PAF had a 4.42 greater odds (95% confidence interval [CI] 1.35 to 14.44) of reporting alcohol consumption (p = 0.014) and a 2.02 greater odds (95% CI 1.02 to 4.00) of reporting vagal activity (p = 0.044) as an arrhythmia trigger compared to patients with SVT. In patients with PAF, drinking primarily beer was associated with alcohol as a trigger (odds ratio [OR] 4.49, 95% CI 1.41 to 14.28, p = 0.011), whereas younger age (OR 0.68, 95% CI 0.49 to 0.95, p = 0.022) and a family history of AF (OR 5.73, 95% CI 1.21 to 27.23, p = 0.028) each were independently associated with having vagal activity provoke an episode. Patients with PAF and alcohol triggers were more likely to have vagal triggers (OR 10.32, 95% CI 1.05 to 101.42, p = 0.045). In conclusion, alcohol consumption and vagal activity elicit PAF significantly more often than SVT. Alcohol and vagal triggers often were found in the same patients with PAF, raising the possibility that alcohol may precipitate AF by vagal mechanisms.     

Buccal Injection of 2% Lidocaine With Epinephrine for the Removal of Maxillary Third Molars

The aim of the study was to demonstrate if 2% lidocaine hydrochloride with 1 : 200,000 epinephrine could provide palatal anesthesia in maxillary tooth removal with a single buccal injection. The subjects included in the clinical study were those requiring extraction of the maxillary third molar of either side. For the purpose of comparison, the sample was randomly divided into 2 main groups: group 1 (study group) included 100 subjects who were to receive a single injection before extraction, and group 2 (control group) included 100 subjects who were to receive a single buccal injection and a single palatal injection before extraction. After 5 minutes the extraction was performed. All patients were observed for Faces Pain Scale during extraction and asked for the same on a 100-mm visual analog scale after extraction. According to visual analog scale and Faces Pain Scale scores, when maxillary third molar removal without palatal injection (study group) and with palatal injection (control group) were compared the difference was not statistically significant (P > .05). Removal of maxillary third molars without palatal injection is possible by depositing 2 mL of 2% lidocaine hydrochloride with 1 : 200,000 epinephrine to the buccal vestibule of the tooth.Key Words: Maxillary third molar, Lidocaine hydrochloride with 1 : 200,000 epinephrine single buccal injection, Local anesthesiaAchieving excellent local anesthesia is the key to many dental treatments. Pain-free operating is an added benefit to the patient but also helps the operator to treat the patient in a calm, unhurried fashion.¹ The removal of maxillary third molars is one of the most frequently performed procedures by dental surgeons. Indications for removal include common pathological conditions such as caries, buccal eruption with food impaction or cheek biting, and recurrent pericoronitis.²According to the literature, for the removal of maxillary third molars, anesthetic solution should be administered as either a greater palatine nerve block or local palatal infiltration plus either a posterior alveolar nerve block or a buccal infiltration.³ Palatal injections are frequently associated with some level of discomfort due to strong attachment of palatal mucosa to the bone and dense innervation of the palatal mucosa. Many studies reported that palatal injections are poorly tolerated by the majority of patients.^3–5Initially there was inadequate evidence in the literature to support maxillary third molar removal with only buccal infiltration of local anesthesia,⁶ but now more studies have evaluated the bucco-palatal diffusion of local anesthesia in extractions with only buccal vestibular anesthesia, without palatal complementation.^7,8Many techniques have been tried to reduce the discomfort of intraoral injections, including transcutaneous electronic nerve stimulation, topical anesthetic application, topical cooling of the palate, computerized injection systems, pressure administration, and eutectic mixture of local anesthetics. Some claim that articaine has a higher potential of diffusibility through soft and hard tissues, precluding palatal injection when maxillary third molars are extracted.^7,9 In a comparative study between articaine and lidocaine, both solutions presented similar behavior and properties.¹⁰The aim of our study was to find out if lidocaine hydrochloride with epinephrine could provide palatal anesthesia in maxillary third molar removal without the need for a palatal injection.     

Substrate for complications

Acute stent thrombosis is a rare, life-threatening, and challenging complication of left main stenting. Equally challenging is treating a chronic saphenous vein graft occlusion. Though considered class III indication per ACC/AHA guidelines, the saphenous vein graft may be the only potential conduit for revascularization. Coronary perforation during chronic total occlusion revascularization after coronary artery bypass grafting is not rare but the post-coronary artery bypass grafting state itself may provide some protection against tamponade by virtue of the adhesions between pericardium and epicardium consequent to surgery. We present a case of multiple complications in one patient and a good outcome after treating each of the above complications.     

Intracranial pressure - volume response in dog subjected to repeated infusion tests: an experimental study

Several experimental studies have been made in the past to try to understand the nature of the fluid-induced changes in the intracranial pressures of the animals by infusing fluid into their craniospinal complex. The objective of the present investigation was to study the changes in the characteristics of the ventricular and epidural pressure-volume curves when a dog was subjected to repeated fluid infusion tests. The animals were subjected to three cycles of infusion tests with a time interval of either 10 min or 2 h between any two successive tests. An infusion test repeated 10 min after the preceding test exhibited a significant change in the characteristics of the ventricular fluid pressure (VFP) response but not in the epidural pressure (EDP) response. However, in the case of an infusion test which was repeated 2 h after the preceding test, it was observed that both the VFP and EDP responses remained the same as those found in the first infusion test.     

The pharmacokinetics of teicoplanin in varying degrees of renal function

The pharmacokinetics of teicoplanin, a new glycopeptide antibiotic with activity against aerobic gram-positive bacteria, were characterized after intravenous administration of a single 3 mg/kg dose in five healthy volunteers and six patients with various degrees of stable renal insufficiency. Serum and urine samples were collected during a 15-day period and drug concentrations were assayed microbiologically. The mean elimination half-life of teicoplanin was 162.6 +/- 69.8 hours in healthy volunteers and was prolonged with decreased renal function. The mean plasma and renal clearances of teicoplanin in healthy subjects were 11.4 +/- 1.5 ml/min and 10.0 +/- 1.0 ml/min, respectively. Both values decreased in patients with renal failure and correlated significantly with measured creatinine clearances (r2 = 0.938 and 0.884, respectively). A nomogram for dosage adjustment in patients with varying degrees of renal failure is presented.