bluuebunny/crossref_metadata_2025 huggingface dataset:
The Loss of PTEN Allows TCR αβ Lineage Thymocytes to Bypass IL-7 and Pre-TCR–mediated Signaling
Authors: Hagenbeek Thijs J. , Naspetti Marianne , Malergue Fabrice , Garçon Fabien , Nunès Jacques A. , Cleutjens Kitty B.J.M. , Trapman Jan , Krimpenfort Paul , Spits Hergen
Published: September 2004

The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates cell survival and proliferation mediated by phosphoinositol 3 kinases. We have explored the role of the phosphoinositol(3,4,5)P3-phosphatase PTEN in T cell development by analyzing mice with a T cell–specific deletion of PTEN. Ptenflox/floxLck-Cre mice developed thymic lymphomas, but before the onset of tumors, they showed normal thymic cellularity. To reveal a regulatory role of PTEN in proliferation of developing T cells we have crossed PTEN-deficient mice with mice deficient for interleukin (IL)-7 receptor and pre–T cell receptor (TCR) signaling. Analysis of mice deficient for Pten and CD3γ; Pten and γc; or Pten, γc, and Rag2 revealed that deletion of PTEN can substitute for both IL-7 and pre-TCR signals. These double- and triple-deficient mice all develop normal levels of CD4CD8 double negative and double positive thymocytes. These data indicate that PTEN is an important regulator of proliferation of developing T cells in the thymus.
Restoration of the Orbital Aesthetic Subunit in Complex Midface Defects
Authors: Chepeha Douglas B. , Wang Steven J. , Marentette Lawrence J. , Bradford Carol R. , Boyd Charles M. , Prince Mark E. , Teknos Theodoros N.
Published: September 2004

Objectives/Hypothesis: Although various options exist for restoration of the orbital defect in complex craniofacial resections, the aesthetic appearance and functional result of the orbit are optimized when the bony orbital architecture, orbital volume, and facial contour are specifically addressed. The study describes an approach using free tissue transfer for restoration of the native orbital aesthetic subunit.

Study Design: Retrospective case series.

Methods: Nineteen patients (male‐to‐female ratio, 14:5; mean age, 52 y [age range, 8–79 y]) in the study period between 1997 and 2001 had orbital defects that could be classified into one of the following categories: 1) orbital exenteration cavities only, 2) orbital exenteration cavities with resection of less than 30% of the bony orbital rim, or 3) radical orbital exenteration cavities with resection of overlying skin and bony malar eminence. Group 1 had reconstructions with fasciocutaneous forearm flaps; group 2, with osseocutaneous forearm flaps; and group 3, with osseocutaneous scapula flaps.

Results: Eighteen of 19 patients achieved a closed orbital reconstruction with restoration of the orbital aesthetic subunit. Among 16 patients with more than 4 months of follow‐up, 10 patients had minimal or no resulting facial contour deformity and 8 patients engaged in social activities outside the home on a frequent basis. Five of the nine patients who were working before their surgery were able to return to work.

Conclusion: Patients with complex midface defects involving the orbit can undergo free tissue transfer and have successful restoration of the native orbital aesthetic subunit without an orbital prosthesis.
Cochlear Implantation in Adults With Prelingual Deafness. Part II. Underlying Constraints That Affect Audiological Outcomes
Authors: Teoh Su Wooi , Pisoni David B. , Miyamoto Richard T.
Published: September 2004

Objectives/Hypothesis: To discuss the underlying physiological and anatomical constraints on audiological performance of late‐implanted prelingually deafened adult cochlear implant patients.

Study Design: Retrospective review.

Methods: Published literature on the topic of auditory pathway responses to prolonged congenital deafness was reviewed. In particular, the authors sought to identify the anatomical and physiological changes that take place in both the peripheral and central auditory pathways in response to prolonged deafness, as well as how they are altered by chronic electrical stimulation.

Results: The currently available evidence suggests that the colonization of the auditory cortex by other sensory modalities is the main limiting factor in postimplantation performance, not the pathological degenerative changes of the auditory nerve, cochlear nucleus, or auditory midbrain.

Conclusion: The reviewed evidence, although circumstantial, suggests that emphasizing aurally based educational programs before (with hearing aids) and after cochlear implantation could reduce the cortical colonization phenomenon and potentially improve postimplantation audiological performance of patients with long‐term prelingual deafness.
Cine Magnetic Resonance Imaging: Evaluation of Persistent Airway Obstruction after Tonsil and Adenoidectomy in Children with Down Syndrome
Authors: Shott Sally R. , Donnelly Lane F.
Published: September 2004

Objective/Hypothesis: Although usually successful, not all obstructive sleep apnea is cured by removal of the tonsils and adenoids (T&A). This is particularly true in children with Down syndrome and craniofacial anomalies. This is because of the multiple levels of obstruction in their airways, with obstruction present not only at the level of the tonsils and adenoids but also from base of tongue obstruction, soft palate collapse, and hypopharyngeal collapse. The cine magnetic resonance image (MRI) is useful in evaluating the upper airway in those patients who have not achieved a normal polysomnogram after T&A surgery.

Study Design: Prospective case series.

Methods: Fifteen children with Down syndrome who had previously undergone a T&A but continued to have abnormal postoperative polysomnograms underwent a cine MRI with fast gradient cine MRI images.

Results: The cine MRI identified different areas and levels of obstruction that ultimately affected the children's treatment courses. Recurrent adenoid tissue, glossoptosis, soft palate collapse, hypopharyngeal collapse, and enlarged lingual tonsils were identified. The results as well as several illustrative cases are presented.

Conclusion: Cine MRI evaluates upper airway obstruction in children who may have multiple sources of obstruction causing their obstructive sleep apnea. This is particularly helpful in children with Down syndrome and craniofacial anomalies. This technology is useful in all children with complex upper airway obstruction.
Laryngeal Amyloidosis in 10 Patients
Authors: Dedo Herbert H. , Izdebski Krzysztof
Published: September 2004

Objectives: Review the location, symptoms, treatment, and outcomes in 10 consecutive laryngeal amyloid (LA) patients.

Study Design: Pre and retrospective evaluation after treatment.

Methods: Analysis of visual and phonatory pathology and detailed description of surgery.

Results: Amyloid on the undersurface of both true vocal cords (TVCs) was found in two cases, uni‐ or bilaterally submucosally in the false vocal cords (FVCs) in eight cases, extending down into the lateral TVC in four cases, or on the undersurface of the TVCs as well in one case. The chief complaint was hoarseness and not shortness of breath. The amyloid was resected with a CO2 laser by way of microdirect laryngoscopy (MDL) on one side at a time to try to prevent anterior commissure scarring. Removal of most of the FVC improved the voice, but removal of the whole FVC to the inner thyroid perichondrium was found to be necessary to avoid recurrence from supraglottic deposits. Removal of at least 2 mm of the upper edge of a 3 to 4 mm thick submucosal deposit to the thyroarytenoid (TA) muscle along with the overlying mucosa on at least one side was necessary to improve hoarseness when amyloid was present on the undersurface of both TVCs. Partial regrowth occurred in a few months to years after partial removal. Seven patients had had one to seven prior removals. Any hard amyloid in the lateral TVC (floor of ventricle) as an inferior extension from FVC amyloid needed to be at least partially removed to avoid hoarseness from a convex vocal cord. The voice improved postoperatively in all patients. Follow‐up after the first operation was 6 months to 16 years, with an average of 6.5 years. Four FVC patients required re‐excision on the same side after the first operation, but none has required a third removal as of yet.
Pediatric Hemophilic Pseudotumor of the Paranasal Sinus
Authors: Steele Natalie P. , Myssiorek David , Zahtz Gerald D. , Diamond Alan
Published: September 2004

Objectives/Hypothesis: Hemophilic pseudotumors are rare clinical entities in otolaryngology. An unusual case of a pediatric hemophilic pseudotumor of the paranasal sinus in a previously undiagnosed hemophiliac is presented.

Study Design: Case report.

Methods: A 6‐month‐old, otherwise healthy boy was admitted for evaluation of a rapidly expanding left‐sided cheek mass. The patient's initial presentation, imaging workup, and intraoperative and postoperative courses are discussed.

Results: Imaging workup revealed a large, heterogeneous, dense lesion in the patient's left‐side maxillary sinus with distortion of the orbital floor and hard palate. Because of the concern for an aggressive malignancy, a biopsy was performed. After a Caldwell‐Luc approach, a large amount of greenish fluid leaked from an otherwise empty maxillary sinus. The patient continued to bleed from his intraoral incision postoperatively and required two packed erythrocyte transfusions. Subsequent hematological testing led to a diagnosis of severe hemophilia type A with factor VIII levels less than 1% of normal. After treatment with recombinant coagulation factors hemostasis was achieved, and the patient clinically improved.

Conclusion: The study presents the first report of a pediatric hemophilic pseudotumor in the paranasal sinuses leading to a diagnosis of hemophilia. It is a rare entity characterized by a cycle of repeated hemorrhage with subsequent encapsulation of the coagulum leading to pressure‐induced distortion of adjacent bone. In the correct clinical setting, hemophilic pseudotumor should be considered in the differential diagnosis of a rapidly expanding mass in children.
Effects of Ascorbic Acid on Oxidative System and Transient Evoked Otoacoustic Emissions in Rabbits Exposed to Noise
Authors: Dereköy Fevzi Sefa , Köken Tülay , Yilmaz Deniz , Kahraman Ahmet , Altuntaş Ali
Published: September 2004

Objectives/Hypothesis: The objective was to investigate the effects of both noise exposure and ascorbic acid on oxidative status and hearing thresholds of rabbits.

Study Design: Randomized prospective animal study comparing oxidative parameters and otoacoustic emissions in two rabbit groups exposed to noise. One group was given absorbic acid, the other group was not given any treatment.

Methods: Two groups of rabbits were used in the study; each group had six rabbits. The six rabbits in the first group were not given any treatment, whereas 500 mg intramuscular ascorbic acid twice daily for 2½ days was given to the six rabbits in the second group. Transient evoked otoacoustic emissions were recorded in all animals before and after noise exposure. Total protein sulfhydryl groups, carbonyl contents, and malondialdehyde levels, as well as erythrocyte glutathione, superoxide dismutase, and catalase enzyme levels, were measured in all rabbits. All the rabbits were exposed to noise (100 dB sound pressure level, 1000 Hz, 1 h), and transient evoked otoacoustic emissions were recorded again.

Results: When oxidative parameters before noise exposure were compared, erythrocyte glutathione and catalase enzyme levels were detected to be higher in the second group (P < .05). In the first group of rabbits after noise exposure, total protein sulfhydryl groups were found to be reduced (P < .05), whereas plasma carbonyl contents and malondialdehyde levels were elevated significantly (P < .05). In this group, erythrocyte glutathione, superoxide dismutase, and catalase enzyme levels were low (P < .05). In the second group, which was given ascorbic acid, total protein sulfhydryl groups were reduced (P < .05), whereas plasma carbonyl contents and malondialdehyde levels did not change (P > .05) following noise exposure. In the second group, erythrocyte glutathione and catalase enzyme levels were reduced (P < .05), but superoxide dismutase levels did not change (P > .05). Transient evoked otoacoustic emissions after noise exposure were weak in both groups, but reproducibility and signal‐to‐noise ratios were higher in the second group (P < .05).

Conclusion: Ascorbic acid treatment inhibited both lipid peroxidation and oxidative damage of proteins in rabbits exposed to noise. The study data suggest, at least, that oxidative status should be included in the physiopathology of noise‐induced hearing loss; in addition, a brief application of ascorbic acid before noise exposure appeared to play a protective role for cochlea.
Amplitude Effects on Electrocochleography Outcomes
Authors: Hough David , Baker R Stanley
Published: September 2004

Objective: Electrocochleography measures in humans were examined to determine factors affecting results.

Study Design: Retrospective study.

Methods: Analysis was performed on data from 479 patients seen from 1998 to 2002 who underwent electrocochleography with a tympanic membrane electrode. Measures from click evoked electrocochleography (the summating potential to action potential ratio [SP/AP]) were compared with tone evoked electrocochleography (the SP amplitude).

Results: Findings indicate a strong correlation between click and tone measures if the AP from click measures was over 1 μV (P < .001), but no significant correlation between these measures if the AP was under 1 μV. Results were also analyzed with respect to patient hearing sensitivity and final diagnosis.

Conclusion: Tympanic membrane electrocochleography is more efficacious when the AP from click stimulation is over 1 μV.
Early Development of the Nose in Human Embryos: A Stereomicroscopic and Histologic Analysis
Authors: Kim Chang‐Hoon , Park Hyoung Woo , Kim Kyubo , Yoon Joo‐Heon
Published: September 2004

Objectives/Hypothesis: To analyze the morphologic features of the nose in the human embryo from the 4th to 8th developmental week according to Carnegie stage.

Study Design: Stereomicroscopic and histologic analysis of the morphology of the human embryo.

Methods: A total of 27 cases of embryos, ranging from Carnegie stage 13 to 23, were analyzed. The external morphology was observed with a stereomicroscope, photographed, and analyzed. The histologic features were observed with a light microscope in the horizontally transected specimens stained with hematoxylin‐eosin.

Results: The nasal placode was observed in stage 13, and it became flat or even concave in stage 14. In stage 15, the nasal pit was formed. In stage 16, the nasal sac and nasal fin were observed. In stage 17, the oronasal membrane was formed by thinning of the nasal fin. In stage 18, the primitive choana was established by a rupture of the oronasal membrane. In stage 19, the lateral palatine process projected vertically below the level of the tongue. The cartilaginous nasal capsule was formed in stage 20. In stage 21, the olfactory area was localized to the upper portion of the lateral nasal wall and the nasal septum. In stage 22, the lateral palatine process developed in a somewhat horizontal orientation. In stage 23, the premaxilla and primitive choana were formed.

Conclusions: The development of the nose is most active from Carnegie stage 13 to 19, which corresponds to the end of the fourth embryonic week to the end of the seventh week. Thus, this period is considered to be the most important period in human nasal embryonic development.
mRNA For Genes Associated with Antigen Presentation are Expressed by Human Middle Meatal Epithelial Cells in Culture
Authors: Lane Andrew P. , Saatian Bahman , Yu Xiao‐Ying , Spannhake Ernst William
Published: September 2004

Objectives/Hypothesis: Although the mechanisms underlying the initiation and maintenance of inflammation in chronic rhinosinusitis are poorly understood, the activation of memory T cells within the nasal mucosa is thought to play an important role. T‐cell activation requires specialized antigen processing and presentation of antigen by immunocompetent cells in the context of cell surface immune molecules. The purpose of this study was to investigate the expression of such molecules by human sinonasal epithelial cells grown in culture at the air‐liquid interface (ALI).

Methods: Middle meatal epithelium was obtained from six patients undergoing endoscopic sinus surgery. Dissociated epithelial cells were grown to confluence in serum‐free, defined medium and transferred to filter inserts for culture at the ALI. Cells were harvested at 2 and 21 days of growth at the ALI and processed for real‐time polymerase chain reaction (PCR). The presence and relative abundance of constitutively expressed mRNA for human leukocyte antigen (HLA)‐B, HLA‐DR, B7 to 1, B7 to 2, B7‐H2, B7‐H3, and cathepsin D were assessed.

Results: After 2 days at the ALI, middle meatal epithelial cells demonstrated expression of genes for each of the antigen processing associated genes tested. The expression of HLA‐B and HLA‐DR increased significantly with cellular maturation at the ALI. Expression of HLA‐DR and B7 to 1 increased with cytokine stimulation.

Conclusions: Primary human epithelial cells obtained from the middle meatus express genes associated with antigen presentation function. The pattern of gene expression is modulated by cytokine stimulation and changes as the cells differentiate at the ALI. These findings suggest that mature middle meatal epithelial cells have the cellular machinery to interact with T cells and therefore may be direct participants in the modulation of T‐cell activity in chronic sinusitis.
Measuring Quality of Life in Children with Adenotonsillar Disease with the Child Health Questionnaire: A First U.K. Study
Authors: Georgalas Christos , Tolley Neil , Kanagalingam Jeevendra
Published: September 2004

Objective: To validate the Child Health Questionnaire (CHQ) and assess the quality of life of inner‐city British children with adenotonsillar disease.

Methods: The primary caregiver of a consecutive series of 43 patients referred for adenotonsillar disease to a pediatric otolaryngology clinic completed the Child Health Questionnaire. Questionnaires were analyzed for data quality and completeness, items/scale correlation, internal consistency and discriminant validity, interscale correlation, reliability estimates and external validity.

Results: CHQ demonstrated excellent measuring characteristics in our population. In a comparison with healthy children, 11 out of 15 measures of quality of life were significantly depressed in our sample. Compared with children with rheumatoid arthritis, scores were equivalent in most areas, with the exception of the global health subscale and overall physical score, where our sample scored significantly lower.

Conclusion: The CHQ (PF 28 version) is an accurate and reliable way of assessing the impact of adenotonsillar disease on the quality of life in children in Britain. This appears to be quite significant in most aspects of a child's life.
How important is TVT location?
Authors: Dietz Hans Peter , Mouritsen Lone , Ellis Gaye , Wilson Peter Donald
Published: September 2004

Background.  The tension‐free vaginal tape (TVT) is claimed to be a midurethral procedure, but data on sling placement are scarce to date. The aim of this study was to investigate tape position and mobility and correlate this with postoperative symptoms of bladder dysfunction.

Methods.  One hundred and forty‐one women 5 weeks to 2.1 years (mean 0.66 years) after TVT placement took part in a prospective clinical observational study. Appointments consisted of standardized symptom questionnaire, clinical stress test flowmetry and translabial ultrasound. The main outcome measures were patient symptoms, subjective satisfaction and cure/improvement. Paired t‐test and anova statistics were employed for continuous, normally distributed parameters.

Results.  Tape position varied from 30 mm above to 12.7 mm below the symphysis at rest and between 15 mm above to 18.7 mm below the symphysis on Valsalva. The horizontal distance of the tape from the symphysis pubis was weakly associated with recurrent stress incontinence (p = 0.048). More cranial tapes were weakly associated with urge incontinence (p = 0.03), frequency (p = 0.048) and symptoms of voiding dysfunction (p = 0.029). There was no association between tape placement and patient satisfaction or subjective cure/improvement.

Conclusions.  Position and mobility of the TVT vary markedly. This may be explained by varying degrees of dissection, localization of incisions and the preoperative degree of anterior vaginal wall prolapse. However, variations in placement seem to have relatively little effect on symptoms.
Urinary tract infection in the users of depot‐medroxyprogesterone acetate
Authors: Ziaei Saeideh , Ninavaei Mojgane , Faghihzadeh Soghrate
Published: September 2004

Background.  The effects of progesterone on muscle tone, peristalsis of the ureter and also urinary vasculature may cause urinary tract infection (UTI) in women who use depot‐medroxyprogesterone acetate (DMPA) for contraception.

Methods.  In a cohort study, 200 women who chose DMPA for contraception were compared with 200 women who used the withdrawal method for urinary infection and urological symptoms after 3 months of consumption.

Results.  The rate of urinary infection and urological symptoms in the study group were higher than in the control group (p = 0.018, p < 0.0001, respectively). The most common microorganism that caused urinary infection was Escherichia coli. Among the 10 cases who suffered UTI in the case group, there were six women who had UTI in the previous pregnancy as well.

Conclusion.  We do not recommended administering depot‐medroxyprogesterone acetate for contraception in women with a history of urinary tract infection in a previous pregnancy.
Sphincter rupture and anal incontinence after first vaginal delivery
Authors: Pinta Tarja M. , Kylänpää Marja‐Leena , Teramo Kari A. W. , Luukkonen Pekka S.
Published: September 2004

Background.  The aim of this prospective study was to establish the incidence of anal incontinence and sphincter defects after first vaginal delivery.

Methods.  A total of 99 nulliparous and pregnant women were examined prospectively 4 weeks (mean) before delivery and 4 months (mean) after delivery. Of the study population, 75 (76%) women had vaginal delivery and 24 (24%) had cesarean section. Vacuum extraction was necessary in 20 (20%) cases. The symptoms of anal incontinence were asked about using a standard questionnaire. Clinical examination, endoanal ultrasound (EAUS) and anal manometry were performed before and after delivery.

Results.  The symptoms of mild anal incontinence, mainly gas incontinence, increased after vaginal delivery more than after cesarean section (P < 0.032). Occult anal sphincter defects were noted in 17 (23%) of the 75 women after vaginal delivery by using EAUS. After vacuum extraction, anal sphincter defects were noted in nine (45%) out of 20 women. No new sphincter defects were found in the cesarean section group. The maximal squeezing pressures were significantly decreased in the patients with external anal sphincter (EAS) defects (P = 0.0025). Vacuum extraction leads to more sphincter defects but does not significantly increase anal incontinence or decrease mean anal sphincter pressures.

Conclusions.  The first vaginal delivery can result in occult sphincter defects and the use of vacuum extraction increases the risk.
Combined genital prolapse repair reinforced with a polypropylene mesh and tension‐free vaginal tape in women with genital prolapse and stress urinary incontinence: a retrospective case–control study with short‐term follow‐up
Authors: De Tayrac Renaud , Gervaise Amelie , Chauveaud‐Lambling Aurelia , Fernandez Herve
Published: September 2004

Background.  To evaluate the tension‐free vaginal tape (TVT) in both stress urinary incontinence (SUI) and occult SUI as an associated procedure at the time of tension‐free polypropylene mesh repair for the treatment of genitourinary prolapse.

Methods.  Forty‐eight consecutive women undergoing surgery for genital prolapse and concurrent SUI from November 1999 to September 2002. Preoperatively, SUI was symptomatic in 29 women and occult in 19, with a positive stress test during repositioning of the prolapse. All patients had urethral hypermobility and none had intrinsic sphincter deficiency. The cystocele repair was performed in all patients according to the technique of tension‐free polypropylene mesh. Twenty‐six women had an associated TVT and 22 had no associated procedure for SUI (control group). The main outcome measures were postoperative SUI, voiding dysfunction, and recurrence of prolapse.

Results.  The median follow‐up was 20 ± 10.1 months (range 7–41). Patient characteristics and preoperative urodynamic evaluation were similar in the two groups. In patients with preoperative SUI, postoperative SUI occurred in 1/15 of the TVT group (6.7%) vs. 5/14 (35.7%) in the control group (p < 0.05), and voiding dysfunction occurred in 2/15 patients of the TVT group (13.3%) vs. 0/14 in the control group (p > 0.05). In patients with preoperative occult SUI, postoperative SUI occurred in 0/11 of the TVT group vs. 1/8 (12.5%) in the control group (p > 0.05), and voiding dysfunction occurred in 3/11 patients of the TVT group (27.3%) vs. 0/8 in the control group (p < 0.05). Anatomic success on prolapse was 88.5% (23/26) and 86.4% (19/22) in the TVT and the control group, respectively (p > 0.05).

Conclusion.  In patients with preoperative SUI, TVT is more efficient than prosthetic cystocele repair alone to prevent postoperative SUI, without differences in voiding dysfunction. In patients with preoperative occult SUI, prosthetic cystocele repair is as efficient as TVT, with a decreased risk of voiding dysfunction.
Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection
Authors: Haanpää Maija , Paavonen Jorma
Published: September 2004

Background.  Genital herpes (GH) causes genital ulcer disease, severe transient pain, and often paresthesias. Whether or not GH can cause urinary retention or chronic neuropathic pain is not well known.

Methods.  We present two immunocompetent patients with GH associated with neuropathic symptoms. We also review the literature on GH and associated neurologic problems.

Results.  Patient 1 had primary herpes simplex virus (HSV)‐2 infection with transient urinary retention and chronic bilateral neuropathic pain in the sacral area. Patient 2 had recurrent HSV‐1 associated with unitaleral chronic neuropathic pain in the sacral area. Although transient urinary retention associated with GH is not uncommon, chronic neuropathic pain has not been reported previously.

Conclusions.  Our cases show that chronic neuropathic pain, that is “pain initiated or caused by a primary lesion or dysfunction in the nervous system,” can follow genital HSV infection.
The prevalence of stress urinary incontinence among women operated on for abdominal wall hernias
Authors: Tok Ekrem C. , Ertunc Devrim , Dilek Umut , Pata Ozlem , Erdogan Ozlem , Aydin Suha
Published: September 2004

The high co‐occurrence of an abdominal wall hernia (AWH) and stress urinary incontinence (SUI) suggests that there is a common factor in the etiopathogenesis of these disorders in these patients.
Clinical and histological safety assessment of rectocele repair using collagen mesh
Authors: Altman Daniel , Mellgren Anders , Blomgren Bo , López Annika , Zetterström Jan , Nordenstam Johan , Falconer Christian
Published: September 2004

Aim.  To clinically and histologically evaluate inflammatory response following rectocele repair using porcine collagen mesh.

Methods.  Seventeen patients underwent rectocele repair using porcine collagen mesh. Inflammatory response was assessed by clinical and histological inflammatory grading pre‐ and postoperatively. Postoperative body temperature, complications and hospital stay was compared with 15 patients undergoing posterior colporraphy.

Results.  Postoperative clinical examination did not demonstrate any inflammatory reaction. There were no significant changes in fibroblast count (P = 0.43), connective tissue density grading (P = 0.54), macrophage count (P = 0.20), inflammatory cell count (P = 0.48), total cell count (P = 0.51), or inflammatory grading (P = 0.87) postoperatively compared with preoperative values. Body temperature was significantly elevated for both the study and control group, although higher for the study group, postoperatively day 1 (P < 0.001). There were no significant differences in hospital stay and postoperative complications.

Conclusion.  Porcine collagen mesh was not associated with an adverse inflammatory response at clinical or histological evaluation and appears to be a safe material when used for rectocele repair.
Anal incontinence after obstetric sphincter tears: incidence in a Norwegian county
Authors: Norderval Stig , Nsubuga Deirdre , Bjelke Christian , Frasunek Josef , Myklebust Idunn , Vonen Barthold
Published: September 2004

Background.  Anal sphincter tears during vaginal delivery are a major cause of anal incontinence. We wanted to assess the incidence in a Norwegian county where primary repairs are performed in four hospitals using similar per‐ and postoperative protocol for the treatment of such injuries.

Methods.  A postal questionnaire was distributed to all women who underwent primary repair of obstetric sphincter tears in the years 1999 and 2000 in the county of Möre and Romsdal. Symptoms of incontinence and fecal urgency were recorded. Incontinence was assessed using the Pescatori score system.

Results.  Clinically detected sphincter tears occurred in 180 of 5123 vaginal deliveries (3·5%). The questionnaire was returned by 156 women (87%). Six women were excluded. Median follow‐up was 25 months (range 4–39). Incontinence was reported by 88 women (59%), restricted to flatus incontinence in 53 cases (35%). Fecal urgency without incontinence was reported by 14 women (9%). Sixty‐three women (42%) reported de novo moderate to severe symptoms. There was no difference in outcome whether the sphincter injury was partial or complete. Mean Pescatori score was 3·7 in women who felt disabled compared with 2·9 in women who did not feel disabled by their incontinence (P < 0·001). Of 29 women who felt disabled, only three had sought medical attention. Fifty‐eight women (39%) had received no information about the sphincter tear before discharge.

Conclusion.  Anal incontinence is common after both partial and complete obstetric sphincter tears. Information before discharge is deficient, and women avoid seeking medical attention when incontinence develops.
Pathology and Pathophysiology of Drug‐Induced Arterial Injury in Laboratory Animals and its Implications on the Evaluation of Novel Chemical Entities for Human Clinical Trials
Authors: Louden Calvert , Morgan D. Gwyn
Published: September 2004

Abstract: In toxicology studies, drug‐induced arterial injury in laboratory animals continues to be a pressing issue of concern, particularly to those engaged in the discovery and development of novel therapies intended for human use. The concern is justifiably magnified because, currently, there is no unequivocal biochemical marker of arterial injury and/or toxicity in animals or man. Therefore, in laboratory animals used for toxicology studies a precise description of arterial lesions in terms of location, distribution and morphologic character is necessary so that a correlation can be drawn between structural damage and derangement of specific cardiovascular functions. The critical nature of the latter cannot be over‐emphasized because this will provide a basis for understanding the mechanism of toxicity, the pathogenesis of the lesion and assessment of human risk. However, in the decision making process, utilization of pattern recognition must be supported by rigorous scientific investigations aimed at establishing a link, where possible, between the deranged cardiovascular function and alterations in cellular, biochemical and molecular events. Conceivably, engagement of the molecular pharmacology target initiates a series of interactive cascades among cellular and non‐cellular arterial components that culminate in organ damage. Therefore, any investigative mechanistic studies aimed at understanding the initiation and development of arterial lesions in laboratory animals must make a conscientious attempt to identify and characterize the molecular target of toxicity.
Lead Induces Endothelium‐ and Ca2+‐Independent Contraction in Rat Aortic Rings
Authors: Valencia Ignacio , Castillo Enrique F. , Chamorro Germán , Bobadilla Rosa A. , Castillo Carlos
Published: September 2004

Abstract: The contractile effect of lead on rat aortic rings was examined. Lead (0.1–3.1 mM) elicited concentration‐dependent but endothelium‐independent contractions, which were unaffected by prazosin (1 μM). The contractile effects of lead were similar when the aortic rings were bathed either in the absence or presence of external Ca2+. Lanthanum (1 mM) but not verapamil (1 μM) inhibited the lead contractions; hence non‐L‐calcium channels are involved in such effect. In addition, lead induced contractions on aortic rings incubated in Ca2+‐free EGTA‐containing solution for 70 min., an experimental condition in which intracellular Ca2+‐stores are depleted. Finally, the contractile effect of lead was not modified by calphostin C (an inhibitor of protein kinase C). In conclusion, the present results suggest that in rat aorta, the lead‐induced contraction is independent of extra‐ and intracellular calcium stores. In addition, the effect of lead is independent of either catecholamines or protein kinase C. It is likely that in rat aorta, lead enters into the smooth muscle cells through non‐L‐calcium channels, and when acting like calcium on the contractile machinery it produces contraction. The differences observed between our results and those obtained by other authors may indicate that the mechanism of the contractile effect of lead varies among the different blood vessels.
High NaCl Intake Decreases both Flow‐Induced Dilation and Pressure‐Induced Myogenic Tone in Resistance Arteries from Normotensive Rats: Involvement of Cyclooxygenase‐2
Authors: Matrougui Khalid , Loufrani Laurent , Lévy Bernard I. , Henrion Daniel
Published: September 2004

Abstract: The effect of high NaCl diet on resistance arteries is not yet fully documented. In order to assess the effect of NaCl on myogenic tone and flow‐induced dilation independent of arterial blood pressure change, we used normotensive rats which did not develop hypertension upon high NaCl intake. Normotensive Wistar Kyoto Rats received a high (8%) or a normal NaCl diet (0.4%). Mesenteric resistance arteries (150 μm, internal diameter) were cannulated in an arteriograph to allow perfusion of arteries under controlled pressure and flow. Pressure‐induced myogenic tone was lower in the high NaCl group than in the control group. Cyclooxygenase inhibition with indomethacin and (N‐(2‐cyclohexyloxy)‐4‐nitro‐phenyl)‐methanesulphonamide, 1 μmol/l) NS 398 (specific cyclooxygenase‐2 inhibitor) similarly decreased myogenic tone in rats fed high NaCl but had no effect in those fed a normal NaCl diet. Flow‐induced dilation was decreased in the high NaCl group. Inhibition of nitric oxide synthesis with NG‐nitro‐L‐arginine methyl ester decreased flow‐induced dilation in both groups. Indomethacin and NS 398 did not change flow‐induced dilation. As shown by immunofluorescence COX‐2 was present in the endothelium of arteries from rats with a high NaCl diet but not in those fed a normal NaCl diet. Thus, chronic high NaCl intake decreased both flow‐induced dilation and myogenic tone in resistance arteries. The chronic high NaCl did not affect the participation of nitric oxide on flow‐induced dilation, but induced the expression of cyclooxygenase‐2, which participates in myogenic tone. These results suggest that high NaCl changes flow and pressure mechanosensing processes and strengthen the hypothesis that sodium ions have an important role in both pressure and flow‐mechanotransduction in vascular cells.
Trimeresurus flavoviridis (Habu Snake) Venom Induces Human Erythrocyte Lysis through Enzymatic Lipolysis, Complement Activation and Decreased Membrane Expression of CD55 and CD59
Authors: Yamamoto Chieko , Tsuru Daisuke , Oda‐Ueda Naoko , Ohno Motonori , Hattori Shosaku , Kim Sung‐Teh
Published: September 2004

Abstract: Trimeresurus flavoviridis (habu snake) bites can be fatal to man because of its virulent venom, which is clinicopathologically classified as haemorrhagic, necrotic, and haemolytic toxins. Trimeresurus flavoviridis venom causes lysis of human erythrocytes in conditions where plasma is present as well as in plasma‐free conditions in a dose‐dependent manner. The haemolytic process requires Ca2+ and Mg2+ ions in the solution. Additionally, the venom initiates activation of the human complement cascade as evidenced by C3a and C5a releases, complement consumption indicated by CH50 and formation of soluble membrane attack complex. The insertion of membrane attack complex into the erythrocyte membranes is morphologically identified by electronmicroscopy. Immunofluorescence analysis reveals that incubation of erythrocytes with the venom decreased cell‐surface expression of CD55 (decay accelerating factor) and CD59 (protectin), which renders erythrocyte more vulnerable to adherent C3 and C5 convertases and to polymerization of C9 into membranes, and may enhance autologous complement‐mediated haemolysis triggered by the venom. Our data demonstrate that Trimeresurus flavoviridis venom induces haemolysis in the presence of plasma by three distinct mechanisms, direct lipolysis through PLA2 activity, activation of the human complement system, and cleavages of CD55 and CD59 from erythrocyte membranes.
Inhibition of Rat Platelet 5‐Hydroxytryptamine Uptake by Chlorpyrifos and Carbaryl
Authors: Sachana Magda , Flaskos John , Nikolaidis Efstathios , Hargreaves Alan , Alexaki‐Tzivanidou Eleni
Published: September 2004

Abstract: The organophosphate insecticide chlorpyrifos and the carbamate insecticide carbaryl were investigated in adult male rats in terms of their effects on the activity of brain monoamine oxidase–A (MAO‐A) activity and on the platelet uptake of 5‐hydroxytryptamine (5‐HT). The activities of brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) were also determined. For each compound two different dosage regimens were employed. In the acute study, chlorpyrifos or carbaryl was administered at a single intraperitoneal dose of 100 mg/kg or 50 mg/kg, respectively. In the subacute study, chlorpyrifos was injected at a daily dose of 20 mg/kg for 7 days, while carbaryl was given at a daily dose of 10 mg/kg for 14 days. Acute chlorpyrifos administration produced a 85.01% inhibition of AChE and a 43.4% inhibition of BuChE but had no effect on MAO‐A activity and 5‐HT uptake. In contrast, subacute chlorpyrifos exposure caused a 94.96% inhibition of AChE and a 85.8% inhibition of BuChE and, also, elicited a significant (35.02%) reduction in the platelet uptake of 5‐HT. MAO‐A activity was not affected. Acute carbaryl administration produced a 56.38% AChE inhibition and a 55.95% BuChE inhibition and also caused a significant (26.36%) decrease in 5‐HT uptake but no change in MAO‐A. Subacute carbaryl exposure failed to affect significantly any of the biochemical parameters determined. Interference with the 5‐HT system by chlorpyrifos and carbaryl could contribute to the toxicity of these pesticides.
Effects of CCK2 Receptor Blockade on Growth Parameters in Gastrointestinal Tract and Pancreas in Rats
Authors: Björkqvist Maria , Norlén Per , Kitano Masayuki , Chen Duan , Zhao Chun‐Mei , Dornonville de la Cour Charlotta , Gagnemo‐Persson Rebecca , Håkanson Rolf
Published: September 2004

Abstract: Gastrin has a growth‐promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin2 (CCK2) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15–20% already within 1–2 days and by about 30% after 4–8 weeks of CCK2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15–20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK2 receptors, exert a growth‐promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa‐preserving effect.
Level of agreement and biopsy correlation using two‐ and three‐tier systems to grade cervical dyskaryosis
Authors: Anderson C. E. , Lee A. J. , McLaren K. M. , Cairns S. , Cowen C. , McQueen F. , Mayer N. J. , Kamel H. M.
Published: September 2004

At present, a three‐tier system is used to grade cervical dyskaryosis in the UK, although the two‐tier Bethesda system is used in the United States, and the British Society for Clinical Cytology has recommended that a two‐tier system be implemented here. In this study, we have retrospectively re‐graded 117 conventional cervical smears using both systems to determine the intra‐ and interobserver variation and compare the cytology grading in both systems with the final histology. The intra and interobserver agreement was moderate using both grading systems, but the agreement between cytology grade and final histology was poor in both the two‐ and three‐tier systems, and slightly worse using two‐tier grading. However, when each of the three histological categories is considered separately the two‐tier system appears to work better. Therefore, changing the way in which cervical dyskaryosis is graded in the UK may result in poorer agreement between the cervical smear result and the final histological diagnosis if introduced without proper training, monitoring and assessment.
Five‐year follow‐up of women with borderline and mildly dyskaryotic cervical smears
Authors: Rana D. N. , Marshall J. , Desai M. , Kitchener H. C. , Perera D. M. , El Teraifi H. , Persad R. V.
Published: September 2004

This study investigated the 5‐year follow‐up status of women with cervical smears showing borderline nuclear changes (BNC) or mild dyskaryosis and the effect of koilocytosis on the outcome. Thirteen per cent of women with cervical smears showing BNC had high‐grade cervical intraepithelial neoplasia (CIN). In contrast, 28% of women with cervical smears showing mild dyskaryosis had high‐grade CIN. The presence of koilocytosis (24% for borderline smears and 34% for mild dyskaryotic smears) did not appear to influence the risk of developing high‐grade CIN. Our results suggest that the simultaneous implementation of the British Society for Clinical Cytology proposed terminology and the colposcopy guidelines from the British Society for Colposcopy and Cervical Pathology could have an impact on colposcopy services.
Volcanoes of the southwestern extension of the active Mariana island arc: New swath‐mapping and geochemical studies
Authors: FRYER P. , SUJIMOTO H. , SEKINE M. , JOHNSON L. E. , KASAHARA J. , MASUDA H. , GAMO T. , ISHII T. , ARIYOSHI M. , FUJIOKA K.
Published: September 2004

Until recently it was thought that the volcanoes of the Mariana island arc of the western Pacific terminated at Tracey Seamount at ∼ 14°N immediately west of Guam. Sea floor mapping in 1995 shows a series of large volcanic seamounts stretching westward for nearly 300 km beyond that point. The morphology, spacing, and composition of those sampled are consistent with their having formed as a consequence of eruption of suprasubduction zone arc magmas. The relationships of the volcanoes to the tectonic processes of subduction of the Pacific plate beneath the southern portion of the Mariana convergent plate margin are becoming increasingly clear as new bathymetry and geochemical data are amassed. The volcanoes along this trend that lie closest to Guam are forming where the center of active extension in the back‐arc basin intersects the line of arc volcanoes. They develop well‐defined rifts that are parallel to rift structures along the extension center, whereas volcanoes of the spreading axis to the north are smaller than the frontal arc volcanoes and tend to form along lineaments. Compositions of lavas from these intersection volcanoes bear some similarities to back‐arc basin basalt, but are on the whole well within the range of compositions for Mariana island arc lavas. The Pacific plate subducts nearly orthogonal to the strike of the trench along the southern part of the Mariana system and the distance to the arc line from the trench axis is only ∼ 150 km. Several deep fault‐controlled canyons on the inner slope of the southern Mariana trench indicate an enhanced tectonic extension of this plate margin. The presence of these active arc volcanoes and the existence of the orthogonal normal faulting along the southern Mariana forearc supports a model of radial extension for formation of the Mariana Trough, a model previously dismissed because of the lack of evidence of these two major geological features.
Effects of Agricultural Cultivation on Demographics of Southern High Plains Amphibians
Authors: GRAY MATTHEW J. , SMITH LOREN M. , BRENES ROBERTO
Published: September 2004

Abstract:  Anthropogenic disturbance of landscapes surrounding wetlands is considered a factor in local and global amphibian declines. Few data exist on the effects of agricultural cultivation of wetland watersheds on amphibians, and results from previous studies are contradictory. Our objective was to test the effects of general anthropogenic land use (cultivation vs. grassland) on the demographics of seven species and three age classes of amphibians in the Southern High Plains of Texas. We partially enclosed 16 playa wetlands (4 per land use per year) with drift fences and pitfall traps and monitored relative daily abundance and diversity from 16 May to 17 October 1999 and 19 April to 18 August 2000. In general, relative abundance (i.e., average daily capture) of New Mexico and plains spadefoots ( Spea multiplicata, S. bombifrons) was greater at cropland than grassland playas; the abundance of other species and diversity of the amphibian assemblage was not affected by land use. Also, abundance generally was greater in 1999 than 2000 for metamorph spadefoots and barred tiger salamanders (Ambystoma tigrinum mavortium). Differences in spadefoot abundance between land‐use types may have been related to low species‐specific vagility, resulting in increased nestedness within disturbed landscapes and reduced abundance of a potential keystone intraguild predator in cropland playas. The yearly difference in amphibian abundance was likely related to annual precipitation, which influenced wetland hydroperiod. Agricultural cultivation surrounding wetlands is associated with the increased abundance of some amphibian species, but other demographic and fitness parameters—such as temporal demographics, body size, and diet diversity—may be negatively affected.