Significance of nasal septal deviation among patients with antrochoanal polyp.

OBJECTIVE: This study aimed to examine the association between nasal septal deviation and antrochoanal polyp. METHODS: This was a retrospective review of medical records and imaging of patients who underwent endoscopic sino-nasal surgery for antrochoanal polyp. RESULTS: Forty-eight patients operated on for antrochoanal polyp between 2009 and 2019 were eligible for the study. The median age was 32 years, and 52.1 per cent were male. Antrochoanal polyp was diagnosed equally in the right and left nasal cavities. Septal deviation was present in 77 per cent of such cases. In 44 per cent of septal deviation cases, the antrochoanal polyp was ipsilateral to the deviation, which was not statistically significant. The type of deviation according to the Mladina classification was not correlated with the laterality of septal deviation and antrochoanal polyp. CONCLUSION: The laterality of the septal deviation was not found to be correlated with that of the antrochoanal polyp. Therefore, performing routine septoplasty during antrochoanal polyp surgery is unnecessary unless the deviation interferes with the complete extraction of the polyp.

Detection and diagnosis of posterior circulation calcification: An interobserver agreement study.

Background: Posterior cerebral ischemic stroke and its underlying causes can be easily misdiagnosed in routine practice. Therefore, more than a third of positive cases can be easily missed during routine CT image reporting unless expert neuroimaging radiologists carefully report it. Objective: To assess the inter-rater agreement level between senior residents and general radiologists and a specialized expert neuroradiologist when detecting and diagnosing posterior cerebral circulation calcification. Methods: This was a cross-sectional observational study. A total of fifteen senior radiology residents (SRRs) and fifteen general radiologists (GRs) at four different hospitals in Riyadh, Saudi Arabia, were included in the study. A total of four CT-scanned brain cases with the presence of posterior circulation calcification (PCC) with different degrees of severity and one brain case with negative PCC were selected. These cases were predefined by expert neuroradiologists at our center. The cases were uploaded into the picture archiving and communication systems (PACS) at four different centers as outsider cases. These cases were then randomly assigned to the participating SRRs and GRs for reporting. All radiologists were blinded to the findings of the cases. Inter-observer agreement was assessed using the weighted kappa coefficient of agreement (k) between the two groups. Results: The cerebral calcification misdiagnosis rate for the SRRs and GRs was > 93% for most of the positive cases. There was 1) poor inter-observer agreement between the SRRs and GRs for the detection of severe posterior cerebral calcification(PCC) in a negative stroke case (agreement for misdiagnosis, k = 0.93; correct diagnosis, k = 0.00), 2) poor inter-observer agreement for mild PCC in a negative stroke case (agreement for misdiagnosis, k = 0.93; correct diagnosis, k = 0.00), 3) moderate PCC in a positive posterior stroke case (agreement for misdiagnosis, k = 0.92; correct diagnosis, k = 0.00), and 4) poor interobserver agreement for severe PCC in a positive posterior cerebral stroke case (agreement for misdiagnosis, k = 0.846; correct diagnosis, k = 0.00). There was excellent agreement between the SRRs and GRs when reporting negative cases of PCC and stroke. Conclusion: Our study concluded that most of the SRRs and GRs missed the diagnosis of posterior cerebral calcification in the presented cases.

α-Lipoic acid blocks the GMCSF induced protease/protease inhibitor spectrum associated with fetal membrane weakening in-vitro.

INTRODUCTION: We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNFα and thrombin induced FM weakening. α-Lipoic-acid (LA) blocks TNFα and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors. METHODS: FM fragments were cultured±LA and then±GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors. RESULTS: GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1). LA inhibited GMCSF-induced FM weakening and all enzymatic changes. Untreated weaker versus stronger regions of fresh FM showed comparable differences in proteases and protease inhibitor patterns to GMCSF-stimulated versus controls. CONCLUSION: LA blocks GMCSF-induced human FM weakening and associated protease increases and inhibitor decreases. The GMCSF-induced spectrum of protease/protease-inhibitor changes is similar to that in the natural weak FM fragments. In concert with previously reported GMCSF-induced changes in MMPs & TIMPs, these other protease and protease-inhibitor changes presumably facilitate FM weakening and rupture. LA blocks these GMCSF effects and therefore may be a useful agent to prevent PPROM.

Closed-suction compared with Penrose drainage after free flap reconstruction in the head and neck.

Microsurgical free flaps are common in head and neck reconstruction, and their techniques and outcomes have continuously improved during the past decades. However, there are variations in practice among surgeons between the use of closed-suction drainage systems and Penrose drains. The proponents of Penrose drains propose that the negative pressure generated by the closed-suction drainage system may harm the microvascular anastomosis. We know of no previous studies that have compared the two drains for microvascular free flap reconstruction, so our aim was to compare them in a single-centre, retrospective review of all patients who had microvascular free flap reconstruction of the head and neck region in our department between 1 November 2010 and 1 September 2017. During this period 84 patients had 87 free flap reconstructions in the head and neck, 43 of which had Penrose, and 44 closed-suction, drainage. We compared the number of complications between the groups including haematomas, seromas, wound infections, anastomostic thrombosis, anastomotic revision, and need for re-exploration. There were no significant differences between the groups, despite a trend toward fewer negative explorations in the closed-suction group. There were no differences in complications between suction and passive drainage systems after microvascular free flaps, which suggests that closed suction drainage could be safely used after free flap reconstruction in the head and neck.

Integrating Patient Safety Education in the Undergraduate Nursing Curriculum: A Discussion Paper.

BACKGROUND: This paper explores the opportunities and challenges for integrating patient safety education in undergraduate nursing curriculum. METHODS: Four dimensions of undergraduate nursing education are examined: National accreditation of nursing programs, building a competency-based nursing education, a model of nursing education and building faculty capacity in patient safety education and research. RESULTS: Incorporating patient safety in a nursing curriculum can be "institutionalized" by making it a pre-requisite for granting program accreditation. At the operational level, transforming undergraduate nursing education to incorporate inquiry-based learning and moving toward competency-based patient safety education are two key requirements for engaging the students with patient safety science. Building faculty capacity who are experts in both patient safety teaching and research remains a key challenge that needs to be addressed to enable a shift in the patient safety "mindset" for future nursing workforce. CONCLUSION: Efforts to introduce patient safety in nursing education are both necessary and timely, and should accommodate students' unique needs and cultural context.

Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma.

OBJECTIVE: Cervical metastases in papillary thyroid carcinoma are associated with increased recurrence. However, their effect on survival remains controversial. This study evaluated literature on the prognostic value of lymph node ratio for loco-regional recurrence and survival in metastatic papillary thyroid carcinoma. METHODS: The PubMed database was systematically searched using the terms 'papillary thyroid carcinoma' and 'lymph node ratio'. Articles addressing the association between lymph node ratio and loco-regional recurrence or survival were identified. RESULTS: Nine retrospective studies were included, comprising 12 400 post-thyroidectomy and neck dissection papillary thyroid carcinoma patients (median age, 48.6 years; 76 per cent females). Lymph node ratio was associated with worse recurrence-free survival in 60 and 75 per cent of studies investigating the effect of central compartment metastases and both central and lateral compartment metastases on recurrence-free survival, respectively. One large population-based study showed an association between lymph node ratio and disease-specific mortality in N1 nodal disease, but failed to maintain the same association when N1b patients were excluded. CONCLUSION: Regional lymph node ratio is an independent predictor for loco-regional recurrence in pathologically staged N1 patients with papillary thyroid carcinoma. Patients with a high lymph node ratio should be closely followed up.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

Visceral basidiobolomycosis: An overlooked infection in immunocompetent children.

Visceral basidiobolomycosis is an unusual fungal infection of viscera caused by saprophyte Basidiobolus ranarum. It is very rare in healthy children and poses a diagnostic challenge due to the non-specific clinical presentation and the absence of predisposing factors. We report a case of gastrointestinal basidiobolomycosis in a 4-year-old healthy girl who presented with a short history of abdominal pain, bleeding per rectum, fever, and weight loss. The diagnosis was based on high eosinophilic count, classical histopathology findings of fungal hyphae (the Splendore-Hoeppli phenomenon), and positive fungal culture from a tissue biopsy. Fungal infection was successfully eradicated with a combined approach of surgical resection of the infected tissue and a well-monitored course of antifungal therapy. The atypical clinical presentation, diagnostic techniques, and the role of surgery in the management of a rare and lethal fungal disease in an immunocompetent child are discussed.

Coefficient of Friction Patterns Can Identify Damage in Native and Engineered Cartilage Subjected to Frictional-Shear Stress.

The mechanical loading environment encountered by articular cartilage in situ makes frictional-shear testing an invaluable technique for assessing engineered cartilage. Despite the important information that is gained from this testing, it remains under-utilized, especially for determining damage behavior. Currently, extensive visual inspection is required to assess damage; this is cumbersome and subjective. Tools to simplify, automate, and remove subjectivity from the analysis may increase the accessibility and usefulness of frictional-shear testing as an evaluation method. The objective of this study was to determine if the friction signal could be used to detect damage that occurred during the testing. This study proceeded in two phases: first, a simplified model of biphasic lubrication that does not require knowledge of interstitial fluid pressure was developed. In the second phase, frictional-shear tests were performed on 74 cartilage samples, and the simplified model was used to extract characteristic features from the friction signals. Using support vector machine classifiers, the extracted features were able to detect damage with a median accuracy of approximately 90%. The accuracy remained high even in samples with minimal damage. In conclusion, the friction signal acquired during frictional-shear testing can be used to detect resultant damage to a high level of accuracy.

Utility and impact of early t(15;17) identification by Fluorescence In Situ Hybridization (FISH) in clinical decision making for patients in Acute Promyelocytic Leukemia (APL).

INTRODUCTION: Acute Promyelocytic Leukemia (APL) is a curable malignancy with studies showing above 90% survival. However, population-based studies looking at survival suggest that approximately 30% of patients with APL die during induction. Early demonstration of t(15;17) will lead to accurate decision making regarding treatment. The aim of this project was to validate earlier time frames for the Abbott Molecular Vysis LSI promyelocytic leukemia (PML)/ retinoic acid receptor alpha (RARA) fluorescence in situ hybridization (FISH) probe (ASR 6-16 h). METHODS: Twenty patients (15 APL cases and five non-APL cases) were selected for validating various hybridization times for the FISH probe. Expected normal signal pattern was two red and two green signals (2R2G), and the most common expected abnormal signal pattern was two fusion (yellow) signals, one red and one green (2F1R1G) and/or one fusion, one red and one green (1F1R1G). RESULTS: The specificity of the probe ranged from 84% at 2 h, 86% at 4 h, 84% at 6 h, and 87% for overnight hybridization. The sensitivity increased from 79% at 2 h, 80% at 4 h, 81% at 6 h to 87% for overnight hybridization. CONCLUSION: Based on the validation studies, we recommend reading of FISH results at the 4-h incubation mark for a preliminary diagnosis and confirmation with overnight hybridization.

Decidual GM-CSF is a critical common intermediate necessary for thrombin and TNF induced in-vitro fetal membrane weakening.

INTRODUCTION: Inflammation/infection and decidual bleeding/abruption are highly associated with pPROM. As no animal model for pPROM exists, we have developed an in-vitro model system for the study of human fetal membrane (FM) weakening/rupture. Using it we have demonstrated that both TNF/IL-1 (modeling inflammation) and thrombin (modeling bleeding) weaken full thickness FM in a dose dependent manner concomitant with inducing biochemical changes similar to those seen in the FM physiological weak zone. METHODS: As the physiological site of infection and bleeding is the choriodecidua (CD), we modified our model system with full thickness FM tissue mounted on modified Transwell culture inserts to permit directional TNF/thrombin exposure on the decidua only (rather than both sides of the FM). After incubation, medium was sampled separately from the CD facing (maternal side) or from the amnion facing (fetal side) compartments and probed for cytokine release and confirmed with western blots. The FM was strength tested within the insert. RESULTS: Full-thickness FM fragments exposed to TNF or thrombin on CD side only showed dose dependent weakening and biochemical changes consistent with previous reports. Concomitantly, GM-CSF increased markedly on the CD but not the amnion side. Numerous proteases including MMP1 and MMP3 also increased on the CD side. Pre-incubation with GM-CSF antibody blocked both thrombin and TNF induced weakening. Finally, GM-CSF weakened FM in a dose dependent manner. DISCUSSION: GM-CSF is a critical common intermediate in the thrombin and TNF FM weakening pathways.

Antibiotic cement-coated rods: an effective treatment for infected long bones and prosthetic joint nonunions.

The treatment of infected nonunions is difficult. Antibiotic cement-coated (ACC) rods provide stability as well as delivering antibiotics. We conducted a review of 110 infected nonunions treated with ACC rods. Patients were divided into two groups: group A (67 patients) with an infected arthrodesis, and group B (43 patients) with an infected nonunion in a long bone. In group A, infected arthrodesis, the success rate after the first procedure was 38/67 (57%), 29/67 (43%) required further surgery for either control of infection or non-union. At last follow-up, five patients required amputation, representing a limb salvage rate of 62/67 (93%) overall. In all, 29/67 (43%) presented with a bone defect with a mean size of 6.78 cm (2 to 25). Of those with a bone defect, 13/29 (45%) required further surgery and had a mean size of defect of 7.2 cm (3.5 to 25). The cultures were negative in 17/67 (26%) and the most common organism cultured was methicillin-resistant staphylococcus aureus (MRSA) (23/67, (35%)). In group B, long bones nonunion, the success rate after the first procedure was 26/43 (60%), 17/43 (40%) required further surgery for either control of infection or nonunion. The limb salvage rate at last follow-up was 43/43 (100%). A total of 22/43 (51%) had bone defect with a mean size of 4.7 cm (1.5 to 11.5). Of those patients with a bone defect, 93% required further surgery with a mean size of defect of 5.4 cm (3 to 8.5). The cultures were negative in 10/43 (24%) and the most common organism cultured was MRSA, 15/43 (35%). ACC rods are an effective form of treatment for an infected nonunion, with an acceptable rate of complications.

Troubling toys: rare-Earth magnet ingestion in children causing bowel perforations.

Ingestion of foreign bodies in the pediatric population is common and magnet ingestion is known to cause a significant morbidity. Rare-earth magnets are small 3-6 mm diameter spherical powerful magnets that are sold as popular desk toys for adults and were previously found in construction toys in attractive colors for children to play with. We describe 2 young healthy children who ingested rare-earth magnets Buckyballs while playing with these magnetic toys and later presented in emergency with acute abdomen. Abdominal imaging revealed several (26 and 5) pieces of rare-earth magnets in the bowel loops. Emergency surgical exploration revealed multiple gastrointestinal perforations and fistula formation at sites of bowel entrapment in between strong magnets apposed to one another. We highlight the potential dangers of rare-earth magnets in children and suggest increasing public awareness about risks involved in rare-earth magnets ingestion by children to overcome this serious public health issue.

A Triad of Congenital Diaphragmatic Hernia, Meckel's Diverticulum, and Heterotopic Pancreas.

Congenital diaphragmatic hernia is a common developmental anomaly encountered by paediatric surgeons. It is known to be associated with extradiaphragmatic malformations, which include cardiac, renal, genital, and chromosomal abnormalities. Herein, we report a newborn born with concurrent congenital diaphragmatic hernia, Meckel's diverticulum, and heterotopic pancreatic tissue. This is the first case report of such a triad with description of possible mechanisms of the development.

Thrombin weakens the amnion extracellular matrix (ECM) directly rather than through protease activated receptors.

INTRODUCTION: Preterm premature rupture of fetal membranes (pPROM) is a major cause of preterm birth. Abruption associated thrombin production, and infection-inflammation associated cytokine production reportedly play major roles in pPROM. Utilizing an in vitro model-system we have confirmed that both thrombin and inflammatory cytokines remodel and biomechanically weaken amnion, the load-bearing component of FM. Also, we have shown thrombin directly weakens isolated amnion but cytokines weaken amnion only indirectly by initially interacting with choriodecidua and releasing unidentified soluble activator(s). This study's purpose was to determine whether thrombin weakens the isolated amnion through thrombin receptor-protease activated receptors (PARs 1,2,3,4), activation of previously secreted extracellular matrix (ECM) enzymes, or by direct action on the ECM. METHODS: Primary amnion cells and isolated amnion were tested for PARs by immunohistochemistry, Western Blot and rtPCR. Cell-free amnion ECM was produced by devitalizing isolated amnion by exposure to UV light and subsequent freeze-thaw cycles. Devitalized amnion membrane explants were incubated with thrombin and biomechanically tested. RESULTS: PARs were not found in amnion or amnion cells. Thrombin induced dose-dependent weakening of devitalized amnion explants. Preincubation with the thrombin inhibitor hirudin prevented thrombin-induced weakening. Thrombin converted pro-MMP2 embedded in the devitalized amnion ECM to multiple active forms. Thrombin also directly digested gelatin gels in zymograms suggesting the possibility of direct degradation of amnion ECM components. DISCUSSION: Thrombin appears to directly weaken the amnion ECM and additionally activates stored pro-MMP2 to active forms that may further enhance amnion ECM degradation. CONCLUSION: Thrombin weakens amnion directly rather than through PARs.

Congenital duodenal obstruction associated with Down's syndrome presenting with hematemesis.

Congenital duodenal obstruction is usually characterized by onset of early vomiting due to high bowel obstruction. Presentation of congenital duodenal obstruction with acute gastrointestinal bleeding is very uncommon. We present an unusual case of congenital intrinsic duodenal obstruction associated with the Down's syndrome presenting with hematemesis secondary to duodenitis. This is a rare presentation of congenital duodenal obstruction associated with Down's syndrome in addition to seven cases previously reported in the English literature.

[Biomechanical characteristics of human fetal membranes. Preterm fetal membranes are stronger than term fetal membranes]. / Biomécanique de la rupture des membranes fœtales. Les membranes fœtales sont plus résistantes avant terme qu'à terme.

The purpose of this study was to determine the biomechanical characteristics of human fetal membranes (FM) throughout gestation. Biomechanical properties were determined for 115 FM of 23-41 weeks gestation using our previously described methodology. The areas of membrane immediately adjacent to the strongest and weakest tested spots were sampled for histomorphometric analysis. Clinical data on the patients whose FM were examined were also collected. FM less than 28 weeks gestation were associated with higher incidence of abruption and chorioamnionitis. Topographically FM at all gestations had heterogeneous biomechanical characteristics over their surfaces with distinct weak areas. The most premature membranes were the strongest. FM strength represented by rupture force and work to rupture decreased with increasing gestation in both weak and strong regions of FM. This decrease in FM strength was most dramatic at more than 38 weeks gestation. The FM component amnion-chorion sublayers were thinner in the weak areas compared to strong areas. Compared to term FM, preterm FM are stronger but have similar heterogeneous weak and strong areas. Following a gradual increase in FM weakness with increasing gestation, there is a major drop-off at term 38 weeks gestation. The FM weak areas are thinner than the stronger areas. Whether the difference in thickness is enough to account for the strength differences is unknown.

The effects of thrombin and cytokines upon the biomechanics and remodeling of isolated amnion membrane, in vitro.

Abruption-induced thrombin generation and inflammation/infection induced cytokine production have both been associated with fetal membrane (FM) weakening and preterm premature rupture of the fetal membranes (PPROM). Using our in vitro model system we have demonstrated that thrombin, and separately the cytokines, tumor necrosis factor-alpha (TNFα) and interleukin-1-beta (IL-1ß), remodel and weaken full thickness FM. Additionally, we have reported that the anti-oxidant and NFκB inhibitor, alpha-lipoic acid (LA), blocks these thrombin and cytokine induced effects. The purpose of these studies was to determine whether thrombin and cytokines directly weaken the amnion membrane (AM), the major load-bearing component of FM. Isolated AM or full thickness FM fragments from unlabored Cesarean deliveries were incubated with thrombin, TNFα, or IL-1ß, for 48 h. Rupture strength (breaking force) of each fragment was thereafter determined using our published methodology. Biochemical evidence of remodeling and apoptosis; immunoreactive Matrix Metalloproteinase 9 (MMP9), Tissue Inhibitor of Matrix Metalloproteinase 3 (TIMP3) and cleaved poly (ADP-ribose) polymerase (C-PARP) levels in tissue extracts, were determined by western blot and densitometry. Thrombin induced a dose-dependent weakening of isolated AM (P < 0.001) coupled with dose dependent increases in PARP cleavage, and reciprocal increases and decreases, respectively, in MMP9 and TIMP3 protein (all P < 0.01). Thrombin receptor activating peptide-6 (TRAP) also weakened isolated AM. Neither TNFα nor IL-1ß weakened isolated AM. However, both cytokines weakened AM when it was incubated together with the choriodecidua as part of full thickness FM (P < 0.001). Cytokine-conditioned choriodecidua medium also weakened isolated AM (P < 0.001). Under conditions in which cytokines weakened the AM, the changes in MMP9, TIMP3 and PARP cleavage were consistent with those seen after thrombin incubation. LA blocked the FM weakening and remodeling effects. In summary, thrombin weakens AM directly whereas cytokines weaken AM indirectly by causing the release of soluble intermediates from the choriodecidua.

Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro.

Cytokine-mediated inflammation and abruption-induced thrombin generation are separately implicated in matrix metalloproteinase (MMP)-mediated weakening of fetal membranes (FM) leading to preterm premature rupture of the fetal membranes (PPROM). At term, FM of both labored vaginal and unlabored Cesarean deliveries exhibit a weak zone overlying the cervix exhibiting ECM remodeling characterized by increased MMP9 protein and activity. We have reproduced these biochemical changes as well as FM weakening in vitro using tumor necrosis factor-alpha (TNF) and interleukin (IL)-1ß, inflammatory cytokines implicated in PPROM. Additionally, we have reported that the antioxidant and NFκB inhibitor alpha-lipoic Acid (LA) blocks these TNF-induced effects. We now present the first direct evidence that thrombin also can induce FM weakening in vitro, and LA treatment inhibits this thrombin-induced-weakening. Full thickness FM fragments from unlabored Cesarean deliveries were incubated with increasing doses of thrombin (0-100 u/ml) for 48 h. Fragments were then strength tested (breaking force and work to rupture) using our published methodology. MMP3 and 9 levels in tissue extracts were determined by Western blot and densitometry. To determine the effect of LA, FM fragments were incubated with control medium or 10 u/ml thrombin, with or without 0.25 mM LA. Strength testing and MMP induction were determined. Thrombin induced a dose-dependent decrease in FM strength (42% baseline rupture force and 45% work to rupture) coupled with a dose-dependent increase in MMP3 and 9 expression (all p < 0.001). Treatment of FM with 0.25 mM LA completely inhibited thrombin-induced FM weakening and MMP expression (all p < 0.001). Thrombin treatment of cultured FM induces mechanical weakening and increased MMP3 and 9. Treatment of FM with LA inhibits these thrombin-induced effects. We speculate LA may prove clinically useful in prevention of PPROM associated with abruption.

Decreased adherence and spontaneous separation of fetal membrane layers--amnion and choriodecidua--a possible part of the normal weakening process.

INTRODUCTION: The fetal membrane (FM) layers, amnion and choriodecidua, are frequently noted to have varying degrees of separation following delivery. FM layers normally separate prior to rupture during in vitro biomechanical testing. We hypothesized that the adherence between amnion and choriodecidua decreases prior to delivery resulting in separation of the FM layers and facilitating FM rupture. METHODS: FM from 232 consecutively delivered patients were examined to determine the extent of spontaneous separation of the FM layers at delivery. Percent separation was determined by the weight of separated FM tissue divided by the total FM weight. Separately, the adherence between intact FM layers was determined. FM adherence was tested following term vaginal delivery (13), term unlabored cesarean section (10), and preterm delivery (6). RESULTS: Subjects enrolled in the two studies had similar demographic and clinical characteristics. FM separation was present in 92.1% of membranes. Only 4.3% of FM delivered following spontaneous rupture of the fetal membranes (SROM) had no detectable separation. 64.7% of FM had greater than 10% separation. FM from term vaginal deliveries had significantly more separation and were less adherent than FM of term unlabored, elective cesarean section (39.0+/-34.4% vs 22.5+/-30.9%, p=.046 and 0.041+/-0.018N/cm vs 0.048+/-0.019N/cm, p<.005). Preterm FM had less separation and were more adherent than term FM (9.95+/-17.7% vs 37.5+/-34.4% and 0.070+/-0.040N/cm vs 0.044+/-0.020N/cm; both p<.001). CONCLUSIONS: Separation of the amnion from choriodecidua at delivery is almost universal. Increased separation is associated with decreased adherence as measured in vitro. Increased separation and decreased adherence are seen both with increasing gestation and with labor suggesting both biochemical and mechanical etiologies. The data are consistent with the hypothesis that FM layer separation is part of the FM weakening process during normal parturition.