Biomedical subjects

John P Gaughan

Publications and source records attributed to John P Gaughan.

At least 19 recordsLinked to original sources

PubMed2007

Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expression patterns in gastric cancer.

Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.

Aged↗

PubMed2006

Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a meta-analysis.

OBJECTIVE: The purpose of this study was to determine the reported diagnostic accuracy, the validity, and the current limitations of fetal Rh genotyping from peripheral maternal blood based on the existing English-written publications. STUDY DESIGN: A search of the English literature describing fetal RhD determination from maternal blood was conducted. From each study, we determined the number of samples tested, fetal RhD genotype, the source of the fetal DNA (maternal plasma, serum, or fetal cells), gestational age, and confirmation of fetal Rh type. The presence of alloimmunization and exclusions of tested samples were noted. For the meta-analysis we calculated composite estimates using 2 random effects models, weighted GLM and Bayesian. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: We identified 37 English-written publications that included 44 protocols reporting noninvasive Rh genotyping using fetal DNA obtained from maternal blood on a total of 3261 samples. A total of 183 (183/3261, 5.6%) samples were excluded from the meta-analysis. The overall diagnostic accuracy after exclusions was 94.8%. The gestational ages ranged between 8 and 42 weeks gestation. Maternal serum and plasma were found to be the best source for accurate diagnosis of fetal RhD type in 394/410 (96.1%) and 2293/2377 (96.5%), respectively. There were 719/783 (91.8%) alloimmunized patients that were correctly diagnosed. There were 16 studies that reported 100% diagnostic accuracy in their fetal RhD genotyping. CONCLUSION: The diagnostic accuracy of noninvasive fetal Rh determination using maternal peripheral blood is 94.8%. Its use can be applicable to Rh prophylaxis and to the management of Rh alloimmunized pregnancies. Improvements of the technique and further study of structure and rearrangements of the RhD gene may improve accuracy of testing and enable large-scale, risk-free fetal RhD genotyping using maternal blood.

DNA↗

PubMed2006

Getting doctors to report medical errors: project DISCLOSE.

BACKGROUND: Despite the number of patient safety incidents that occur in hospitals, physicians currently may not have the ideal incident reporting tools for easy disclosure. A study was undertaken to assess the effectiveness of a simplified paper incident reporting process for internal medicine physicians on uncovering patient safety incidents. DESIGN: Thirty-nine internal medicine attending physicians were instructed to incorporate the use of a simplified paper incident reporting tool (DISCLOSE) into daily patient rounds during a three-month period. All physicians were surveyed at the conclusion of the three months. RESULTS: Compared with physician reporting via the hospital's traditional incident reports from the same time period, a higher number (98 incidents versus 37; a 2.6-fold increase) of incidents were uncovered using the DISCLOSE reporting tool in a larger number of error categories (58 versus 14, a 4.1-fold increase). When reviewed and classified with a five-point harm scale, 41% of events were judged to have reached patients but not caused harm, 33% to have resulted in temporary harm, and 9% of reports, though not considered events, were to indicate a "risky situation." Surveyed physicians were more satisfied with the process of submitting incident reports using the new DISCLOSE tool. DISCUSSION: A simplified incident reporting process at the point of care generated a larger number and breadth of physician disclosed error categories, and increased physician satisfaction with the process.

Attitude of Health Personnel↗

PubMed2006

Morphine withdrawal lowers host defense to enteric bacteria: spontaneous sepsis and increased sensitivity to oral Salmonella enterica serovar Typhimurium infection.

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyer's patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pellet-withdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice were Enterococcus faecium followed by Klebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated with S. enterica 24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased the Salmonella burden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.

Animals↗

PubMed2006

Thyroidectomy for Graves' disease: a case-control study.

OBJECTIVES: The most common treatment for Graves' disease in the United States is radioactive iodine. Surgery is performed rarely. The surgery for Graves' disease is usually considered technically difficult. Our goal was to assess the differences in outcomes in patients with Graves' disease who underwent thyroidectomy and in patients without Graves' disease who underwent the same procedures. METHODS: A retrospective chart review was performed of patients who underwent surgery for Graves' disease between 1997 and 2005. A control group of age-matched and thyroid size-matched patients who underwent thyroidectomy for a diagnosis other than Graves' disease was identified. The groups were statistically compared with respect to length of hospital stay, operative time, and estimated blood loss. Comparison with the published literature was also performed. RESULTS: Eleven patients underwent thyroidectomy for a diagnosis of Graves' disease. The operative time, estimated blood loss, and length of hospitalization did not differ significantly from those of the control patients. Three of the 4 complications that occurred, however, were in the 3 patients with persistent hyperthyroidism despite medical therapy at the time of surgery. CONCLUSIONS: Thyroidectomy may be performed relatively safely for selected euthyroid patients with Graves' disease. In those with persistent hyperthyroidism at surgery, there were more complications.

Adolescent↗

PubMed2006

The use of somatosensory evoked potentials to determine the relationship between patient positioning and impending upper extremity nerve injury during spine surgery: a retrospective analysis.

Somatosensory evoked potential (SSEP) monitoring is used to prevent nerve damage in spine surgery and to detect changes in upper extremity nerve function. Upper extremity SSEP conduction changes may indicate impending nerve injury. We investigated the effect of operative positioning on upper extremity nerve function retrospectively in 1000 consecutive spine surgeries that used SSEP monitoring. The vast majority (92%) of upper extremity SSEP changes were reversed by modifying the arm position and were therefore classified as position-related. The incidence of position-related upper extremity SSEP changes was calculated and compared for five different surgical positions: supine arms out, supine arms tucked, lateral decubitus position, prone arms tucked, and the prone "superman" position. The overall incidence of position-related upper extremity SSEP changes was 6.1%. The lateral decubitus position (7.5%) and prone superman position (7.0%) had a significantly more frequent incidence of position-related upper extremity SSEP changes (P < 0.0001, Z-test for Poisson counts) compared with other positions (1.8%-3.2%). No patient with a reversible SSEP change developed a new postoperative deficit in the affected extremity. SSEP monitoring is of value in identifying and reversing impending upper extremity peripheral nerve injury.

Adolescent↗

PubMed2006

Low-intensity exercise training improves survival in Dahl salt hypertension.

PURPOSE: The present study examined whether exercise training could increase survival in a rodent model of salt-sensitive hypertension. METHODS: Male, inbred Dahl salt-sensitive rats arriving at 8 wk of age were randomly divided into a sedentary control group (N = 5) or an exercise-trained group (N = 8). Exercise training consisted of running 20 m.min(-1), 0% incline, 60 min.d(-1), 5 d.wk(-1) on a motorized driven treadmill. On arrival, animals were fed a low-salt diet (0.12% NaCl) during a 1-wk acclimatization period. At the end of this period, all rats were then fed a high-salt diet (7.8% NaCl) for the remainder of the study. Arterial systolic blood pressure (SBP) was measured via the tail-cuff method. RESULTS: Systolic blood pressure (SBP) measured on the low salt diet was similar between groups. After 2 wk of a high-salt diet, SBP was similarly significantly elevated in both control and exercise groups relative to the low salt diet. Kaplan-Meier analysis showed that exercise training increased survival (P < 0.02) with an approximate 30% increase in the mean days survived with exercise training (P < 0.02). CONCLUSION: These data suggest that exercise training is an important intervention for salt-sensitive hypertension and that the enhanced survival observed with exercise training appears to be independent of training-induced SBP lowering effects.

Animals↗

PubMed2005

Effect of acute unloading via head-up tilt on QTc prolongation in patients with ischemic or non-ischemic cardiomyopathy.

Patients with advanced cardiomyopathy develop prolongations in ventricular myocyte action potential duration that are reflected by prolongations of QT intervals on surface electrocardiograms. Recent studies demonstrate that the placement of a left ventricular (LV) assist device, which induces profound cardiac decompression, acutely increases QT intervals within hours. The goal of this study was to use head-up tilt (HUT) to examine electrocardiographic responses to cardiac unloading in patients with cardiomyopathy. Surface electrocardiograms were analyzed during HUT in 21 patients with cardiomyopathy (ejection fraction <30%) and in 33 age-matched controls. Four to 6 different QT and RR intervals were measured at baseline (supine), at 5 and 25 minutes after HUT. The heart-rate-adjusted QT interval (QTc) was calculated using Bazett's formula. The mean QTc in control patients decreased at 5 minutes (426 +/- 31 vs 418 +/- 28 ms, p < 0.05, vs supine) and was unchanged at 25 minutes (426 +/- 31 vs 423 +/- 25 ms, p = NS, vs supine). However, in patients with cardiomyopathy, there was a significant increase in QTc during HUT (455 +/- 45 vs 473 +/- 42 and 479 +/- 42 ms, p < 0.001, vs supine). The change in heart rate during HUT did not differ between patients with cardiomyopathy and controls. In conclusion, HUT is associated with the immediate prolongation of myocardial repolarization in patients with cardiomyopathy. This response was not seen in age-matched controls. These results suggest that adaptations to chronic cardiac distention may include processes that help accelerate repolarization. Conversely, the prolongation of repolarization after unloading may modulate myocardial relaxation and arrhythmogenic risk.

Aged↗

PubMed2005

A role for B cell-activating factor of the TNF family in chemically induced autoimmunity.

After exposure to subtoxic doses of heavy metals such as mercury, H-2s mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we observe that HgCl2 administration in susceptible mice results in the elevated production of B cell-activating factor of the TNF family ((BAFF) also known as BLyS, TALL-1, zTNF-4, THANK, and TNSF13B), a B cell growth factor belonging to the TNF family. A transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)-Ig fusion protein (which neutralizes both BAFF and a proliferation-inducing ligand (APRIL), another TNF family member) inhibited Hg-induced autoantibody or serum IgE production. These results are discussed in the context of the inhibitory effect of TACI-Ig on B cell maturation at the transitional stage.

Animals↗

PubMed2005

Vaginal hysterectomy for the enlarged uterus.

OBJECTIVE: To evaluate the effect of uterine weight on the perioperative outcomes of vaginal hysterectomy for benign gynecological conditions. MATERIALS AND METHODS: The medical records of 312 consecutive women who underwent vaginal hysterectomies for benign gynecological conditions without major pelvic reconstruction at Temple University Hospital between March 1994 and August 1999 were reviewed. 88 women with uterine weights > or =250 g were compared with 224 women with uterine weights <250 g. The risk of perioperative complications, operative time, perioperative hemoglobin change, length of postoperative hospital stay, and readmission were evaluated between the groups. RESULTS: Groups were similar with respect to age, parity, history of previous pelvic surgery and concurrent adnexal removal. Operative time was significantly increased for women with uteri weighing > or =250 g. Women with uterine weight > or =250 g had a higher risk for postoperative febrile morbidity. The risks of all other major complications, perioperative change in hemoglobin concentration, length of stay, and readmission risk were not statistically different between the groups (p < 0.05). CONCLUSIONS: Despite the increased postoperative febrile morbidity and prolonged operative time, women with uteri weighing > or =250 g who underwent vaginal hysterectomy were discharged from the hospital without any increase in other complications when compared to women with a smaller uterus.

Female↗

PubMed2005

Risk factors for obstetrical anal sphincter lacerations.

The objective of this study was to identify the rate of anal sphincter lacerations in a large population-based database and analyze risk factors associated with this condition. Data were obtained from Pennsylvania Healthcare Cost Containment Council (PHC4) regarding all cases of obstetrical third and fourth degree perineal lacerations that occurred during a 2-year period from January 1990 to December 1991. Modifiable risk factors associated with this condition were analyzed, specifically episiotomy, forceps-assisted vaginal delivery, forceps with episiotomy, vacuum-assisted vaginal delivery, and vacuum with episiotomy. There were a total of 168,337 deliveries in 1990 and 165,051 deliveries in 1991 in Pennsylvania. Twenty-two percent (n = 74,881) of the deliveries were by cesarean section and were excluded from analysis. Among the remaining 258,507 deliveries, there were 18,888 (7.3%) third and fourth degree lacerations. Instrumental vaginal delivery, particularly with use of episiotomy, increased the risk of laceration significantly [forceps odds ratio (OR): 3.84, forceps with episiotomy OR: 3.89, vacuum OR: 2.58, vacuum with episiotomy OR: 2.93]. Episiotomy on the whole was associated with a threefold increase in the risk of sphincter tears. However, episiotomy in the absence of instrumental delivery seems to be protective with an OR of 0.9 [95% confidence interval (CI): 0.88-0.93]. Instrumental vaginal delivery, particularly forceps delivery, appears to be an important risk factor for anal sphincter tears. The risk previously attributed to episiotomy is probably due to its association with instrumental vaginal delivery. Forceps delivery is associated with higher occurrence of anal sphincter injury compared to vacuum delivery.

Adolescent↗

PubMed2005

ICOS-B7 homologous protein interactions are necessary for mercury-induced autoimmunity.

After exposure to subtoxic doses of heavy metals such as mercury, H-2(s) mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we explore the role of one of the members of the CD28-B7 costimulation families, ICOS-B7 homologous protein (B7h), in the regulation of mercury-induced autoimmunity. The expression of ICOS on T cells was more enhanced in susceptible A.SW mice than in non-responsive C57BL/6 and DBA/2 mice after HgCl(2) treatment. Furthermore, in A.SW mice treated with HgCl(2), administration of a blocking anti-ICOS Ab effectively inhibited anti-nucleolar autoantibodies and total serum IgE production. Taken together, these results indicate that the ICOS-B7h costimulation pathway is required for this autoimmune syndrome and suggest that targeting this pathway might have therapeutic benefits for human autoimmune diseases.

Animals↗

PubMed2005

Impaired vasoreactivity in end-stage heart failure patients on intravenous inotropic support.

BACKGROUND: Vasoreactivity is known to be impaired in heart failure patients; however, it has not been determined whether standard medical therapy for end-stage heart failure patients (ES-HF) ameliorates this impairment. Therefore, we sought to investigate flow-mediated dilation (FMD) responses in ES-HF with normal or near normal cardiac indices from continuous inotropic support. METHODS AND RESULTS: Vascular ultrasound was used to assess FMD responses to isometric exercise and cuff occlusion in 15 ES-HF patients and 5 control subjects (C). ES-HF patients had significant hyperemic response to maximal exercise (P < .05), which was blunted relative to C (ES-HF; 84 +/- 21 mL/min versus C; 299 +/- 85 mL/min, P < .05). ES-HF patients did not show a significant hyperemic response to submaximal exercise. C had a significant increase in arterial diameter that exceeded ES-HF after both maximal (C; 8 +/- 1% versus. ES-HF; -0.9 +/- 0.86%, P < .05) and submaximal exercise (C; 6 +/- 1% versus ES-HF; 0.57 +/- 1%, P < .05). FMD responses at similar absolute workloads showed that both the mean hyperemic response and the change in arterial diameter were significantly greater in C. After cuff occlusion, the mean hyperemic response for ES-HF was again significantly blunted compared with C (ES-HF; 117 +/- 26% versus C; 352 +/- 86%, P < .05). After cuff occlusion, arterial diameter in C significantly increased in response to hyperemia, whereas ES-HF patients had a paradoxical vasoconstrictive response (C; 10.7 +/- 1.1% versus ES-HF; -5.3 +/- 1.5%, P < .05). CONCLUSION: Peripheral vasoreactivity in response to either maximal exercise, submaximal exercise, or hyperemic stimuli is impaired in ES-HF patients with normal resting cardiac outputs.

Blood Flow Velocity↗

PubMed2005

Subvalvular alterations promote increased mitral valve regurgitation in progressive dilated cardiomyopathy.

BACKGROUND: Alterations in transmitral pressure, valve structure, subvalvular geometry, and abnormal myocardial function have all been implicated in the pathophysiology of functional/progressive mitral valve regurgitation (MR). In this study, we hypothesized that a relatively small structural lesion to the mitral valve apparatus predisposes to severe MR in the setting of progressive left ventricular dilation. While examining this hypothesis, an additional purpose of this study was to determine the extent of papillary muscle (PM) distortion and mitral annular dilation with increasing MR resulting from progressive dilated cardiomyopathy. METHODS AND RESULTS: Mild MR was produced via a limited, fixed structural lesion to the mitral valve apparatus of 8 dogs (20 to 22 kg). Incremental tachypacing induced left ventricular dilation over an 8-month period. The pacer was deactivated and the dogs followed for an additional 6 weeks. Echocardiographic measurements demonstrated significant cardiac remodeling (left ventricular end diastolic diameter) and MR progression with a 54% increase in left ventricular end diastolic diameter and a 44% increase in MR jet area (P < .05). Tachypacing induced decreases in left ventricular ejection fraction recovered nearly to baseline levels by 6 weeks after pacing cessation. Nevertheless, left ventricular dilation persisted and MR remained severe after pacing cessation. There was a significant increase in the short axis PM segment length and PM angular separation from baseline (6.28 +/- 0.83 versus 4.02 +/- 0.56 cm and 99.7 +/- 2.6 versus 90.1 +/- 3.2 deg, respectively, P < .05) with no change in mitral annulus circumference (8.71 +/- 0.70 versus 8.15 +/- 0.35 cm, P = NS). CONCLUSION: Progressive MR severity in nonischemic dilated cardiomyopathy resulted from changes in left ventricular shape and altered papillary muscle geometries and does not require mitral annulus dilation or a reduced left ventricular ejection fraction.

Animals↗

PubMed2005

The Na+/Ca2+ exchanger/SR Ca2+ ATPase transport capacity regulates the contractility of normal and hypertrophied feline ventricular myocytes.

BACKGROUND: Pressure overload leads to cardiac hypertrophy, which is often followed by heart failure. We tested the hypothesis that depressed contractility in this process results from an imbalance in Ca 2+ transport by the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) and the sarcolemmal Na+/Ca2+ exchanger (NCX). METHODS AND RESULTS: Left ventricular (LV) myocytes (n = 79) from 12 normal (N) and 5 hypertrophied (LVH, by aortic banding) feline hearts were studied. Adenoviral gene transfer was used to introduce green fluorescent protein (GFP), SERCA2, and NCX into N and LVH myocytes. Contraction (videomicroscopy) and Ca2+ transients (Fluo-3) were measured in steady state and after rest periods of 2 to 120 seconds (rest decay and potentiation). LVH hearts were significantly larger than N (7.1 +/- 1.4 versus 4.2 +/- 0.2 g/kg). SERCA protein was significantly less abundant in LVH versus N. Steady state contractions and Ca2+ transients of LVH-GFP myocytes decayed more slowly and rest decay of contractility was more pronounced compared with N-GFP. Infection of LVH (and N) myocytes with SERCA increased basal contractility and reduced rest decay. Infection of LVH myocytes with NCX almost abolished contraction and in N myocytes reduced contractility and increased rest decay. CONCLUSION: These findings suggest that an imbalance of Ca2+ transport by SERCA and the NCX produces the characteristic contractile abnormalities of hypertrophied cardiac myocytes.

Animals↗

PubMed2005

Trends in the rate of shoulder dystocia over two decades.

OBJECTIVE: To describe the trend in the rate of shoulder dystocia over twenty-four years and identify the risk factors related to the occurrence of dystocia. METHODS: Data was obtained from Maryland State regarding all vaginal deliveries that occurred during six different time periods at five-year intervals since 1979. Trends in the rate of shoulder dystocia, episiotomy, forceps and vacuum delivery were examined. RESULTS: There were a total of 277 974 vaginal deliveries. The overall rate of shoulder dystocia was 1.29% (n = 3590). Induction of labor (adjusted OR 1.2, 1.1-1.3), presence of diabetes (gestational (OR 1.9, 1.7-2.3) or pre-gestational (OR 3.8, 2.7-5.4)), fetal macrosomia (OR 5.1, 4.1-6.3) use of episiotomy (OR 1.6, 1.5-1.8), forceps (OR 1.3, 1.0-1.8) or vacuum (OR 2.3, 2.0-3.9) at delivery were associated with a higher rate of shoulder dystocia. TREND: There was an increase in the rate of shoulder dystocia from 0.2% in 1979 to 2.11% in 2003. In addition there was a drop in the overall episiotomy rate from 73.67% to 23.94% and increase in the use of vacuum from 0.1% to 8.36%. CONCLUSION: The rate of shoulder dystocia has increased by 10 fold during the study period. The use of episiotomy either at spontaneous delivery or instrumental delivery does not appear to decrease the occurrence of shoulder dystocia.

Adolescent↗

PubMed2005

Risk of recurrence of anal sphincter lacerations.

OBJECTIVE: To estimate the rate of recurrence of anal sphincter lacerations in subsequent pregnancies and analyze the risk factors associated with recurrent lacerations METHODS: Data were obtained from the Pennsylvania Health Care Cost Containment Council, Division of In-Patient Statistics, regarding all cases of third- and fourth-degree perineal lacerations that occurred during a 2-year period (from January 1990 through December 1991). All subsequent pregnancies in this group of women over the next 10 years were identified, and the rate of recurrence of sphincter tears and risk factors for recurrence were analyzed. RESULTS: The rate of anal sphincter lacerations was 7.31% (n = 18,888) during the first 2 years of study (1990-1991). In the next 10 years, these patients with prior lacerations were delivered of 16,152 pregnancies. Of these, 1,162 were by cesarean. Among the 14,990 subsequent vaginal deliveries, 864 (5.76%) had a recurrence of a third- or fourth-degree laceration. Women with prior fourth-degree lacerations had a much higher rate of recurrence than those with prior third-degree laceration (7.73% versus 4.69%). The rate for recurrent lacerations was significantly lower than the rate for initial lacerations (odds ratio 1.29, 95% confidence interval [CI] 1.2-1.4). Forceps delivery with episiotomy had the highest risk for recurrent laceration (17.7%, odds ratio 3.6, 95% CI 2.6-5.1), whereas vacuum use without episiotomy had the lowest risk (5.88%, odds ratio 1.0, 95% CI 0.6-1.7). CONCLUSION: Prior anal sphincter laceration does not appear to be a significant risk factor for recurrence of laceration. Operative vaginal delivery, particularly with episiotomy, increases the risk of recurrent laceration as it does for initial laceration. LEVEL OF EVIDENCE: III.

Adolescent↗

PubMed2005

Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.

Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.

Androstadienes↗