Management of Recurrent Stricture Formation after Transverse Vaginal Septum Excision.

Background. A transverse vaginal septum (TVS) is a rare obstructing anomaly, caused due to improper fusion of Müllerian ducts and urogenital sinus during embryogenesis. Case. A 15-year-old girl presented with primary amenorrhea. She had multiple congenital anomalies. Initial examination and imaging investigation revealed the presence of a unicornuate uterus and a TVS. The TVS was excised; however the patient was unable to perform vaginal dilation postoperatively leading to recurrent stricture formation. She underwent multiple surgeries for excision of the stricture. The patient was eventually evaluated every day in the clinic until she was able to demonstrate successful vaginal dilatation in the presence of a clinician. Summary and Conclusion. Properly guided regular and intensive vaginal dilation after TVS excision may decrease the need of reoperations due to recurrent stricture formation.

Bile acid aspiration associated with lung chemical profile linked to other biomarkers of injury after lung transplantation.

Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids in the BALF) to identify potential metabolic changes associated with aspiration. Paired samples, one with bile acids and another without, from 29 stable lung transplant patients were studied. Liquid chromatography coupled to high-resolution mass spectroscopy was used to interrogate metabolomic contents of these samples. Data were obtained for 7068 ions representing intermediary metabolites, environmental agents and chemicals associated with microbial colonization. A substantial number (2302) differed between bile acid positive and negative samples when analyzed by false discovery rate at q = 0.01. These included pathways associated with microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals associated with bile acid aspiration that were correlated to previously reported biomarkers of lung injury including T cell granzyme B level and the chemoattractants CXCL9 and CXCL10. These data specifically link bile acids presence in lung allografts to inflammatory pathways known to segregate with worsening allograft outcome, and provide additional mechanistic insight into the association between reflux and lung allograft injury.

Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant.

Outcomes following lung transplant are suboptimal owing to chronic allograft failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice and humans has shown that interferon gamma (IFNG)-induced chemokines, including CXCL9 and CXCL10, are elevated in patients with established BOS. We hypothesized that patients who ultimately developed BOS would have elevations in these chemokines before losing lung function. We utilized a high throughput multiplex enzyme-linked immunosorbent assay (ELISA) to measure biomarkers in bronchoalveolar lavage fluid (BALF). We modeled cumulative exposure to seven biomarkers (CXCL9, CXCL10, RANTES, IL1-RA, IL-17, MCP1 and IL-13) by calculating the 1-year area under the curve (AUC) for each biomarker in the BALF of 40 lung transplant patients who had at least four samples obtained in the first year posttransplant. Cumulative elevations in CXCL9 and CXCL10 were associated with a significant risk of subsequent graft failure after transplant (HR 9.37 and 5.52, respectively; p < 0.01 for both). Further these chemokines were also elevated in patients before the onset of BOS. CXCL9 and CXCL10 elevations were seen between 3 and 9 months before graft failure. Our data show that persistent presence of CXCL9 and CXCL10 portents worsening lung allograft function; measuring these IFNG-induced chemokines might prospectively identify patients at risk for BOS.

Cumulative exposure to CD8+ granzyme Bhi T cells is associated with reduced lung function early after lung transplantation.

Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoalveolar lavage (BAL) in acute rejection. We hypothesized that persistent exposure to T cells high in granzyme B would negatively correlate with lung function. We investigated cumulative exposure measured as the area-under-the-curve (AUC) of CD8+ T cell granzyme Bhi cells in the first year posttransplant in both BAL and blood in 24 transplant recipients. We assessed the correlation between cumulative 1-year exposure and FEV1 slope. There was a negative correlation between 1-year exposure and FEV1 slope within the first year (r=-0.63; P=.001). This relationship persisted even when adjusted for transplant type, gender, age, rejection, and indication for transplantation. In contrast, no relationship was seen with the 1-year AUC and lung function after 1 year posttransplant. In contrast to the BAL granzyme Bhi levels, granzyme Bhi levels from the blood showed no relationship with lung function. These findings suggest that CD8+ T-cell-driven factors are responsible for early improvements in lung function after transplantation.

Serum and peritoneal fluid antiendometrial antibodies in assisted reproduction.

OBJECTIVE: To study the impact of surgically verified endometriosis and serum and peritoneal fluid antiendometrial antibodies (AEA) on pregnancy outcomes in gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT) and in vitro fertilization (IVF) patients using assisted reproductive technologies (ART). STUDY DESIGN: Surgical evaluation of endometriosis and collection of serum and peritoneal fluid was performed at the time of laparoscopy. For patients who did not undergo laparoscopy, only serum samples were obtained. Sera and peritoneal fluid were tested by indirect immunofluorescence for AEA. RESULTS: There was no correlation between surgically verified endometriosis, serum or peritoneal fluid AEA and clinical pregnancy in patients undergoing ART. There was no significant difference in surgically verified endometriosis in patients who delivered and those who miscarried (p < 0.0594), whereas serum (p < 0.0223) and peritoneal fluid (p < 0.0032) AEA showed differences. In the total group of 352 ART patients, positive serum AEA was statistically significant in those who miscarried vs. those who delivered (p < 0.0000). CONCLUSION: Endometriosis does not significantly impair the pregnancy potential of ART patients, but it may be associated with miscarriage. The presence of serum and peritoneal fluid AEA correlate better with miscarriage than surgically verified endometriosis.

Double vs. single intrauterine insemination per cycle: use in gonadotropin cycles and in diagnostic categories of ovulatory dysfunction and male factor infertility.

OBJECTIVE: To evaluate the effectiveness of offering double intrauterine insemination (IUI) to clients in our fertility program. STUDY DESIGN: In this prospective, nonrandomized study, 595 couples with ovulatory dysfunction, endometriosis, male factor, unexplained, tubal factor and combined diagnoses utilizing clomiphene citrate-hCG (CC-hCG), CC-gonadotropin-hCG (CC-Gn-hCG), Gn-hCG, lupron-Gn-hCG (L-Gn-hCG) or luteinizing hormone (LH) surge monitoring of natural cycles were offered single or double IUI in a total of 1276 cycles. Single IUIs were performed at 36 hours following hCG or the day following LH surge; double IUIs were performed 18 and 36 hours following hCG or the day of and day following LH surge. Single versus double IUI clinical pregnancy outcomes were compared between ovarian stimulation protocols and diagnostic categories. RESULTS: One hundred ten clinical pregnancies occurred for 508 couples in 999 single IUI cycles (fecundity, 11.0%); 45 clinical pregnancies for 174 couples occurred in 277 double IUI cycles (16.2%, p < 0.004). The single IUI group was younger than the double IUI group (32.8 vs. 33.7, p < 0.004). Differences for fecundity were noted regarding diagnostic categories between single and double IUI groups (ovulation dysfunction, 12.9% vs 19.5%, p < 0.048, and male factor, 7.9% vs. 17.5%, p < 0.030) and ovulation protocols (CC-Gn-hCG, 13.0% vs. 21.3%, p < 0.031, and L-Gn-hCG, 4.2% vs. 25.0%, p < 0.002). CONCLUSION: Double IUI is superior to single IUI overall, especially when comparing Gn-containing ovarian stimulation protocols or within the ovulatory dysfunction and male factor diagnostic categories.

Intrauterine insemination results in couples requiring extended semen transport time.

PURPOSE: The purpose of the present study is to compare intrauterine insemination (IUI) pregnancy rates (PR) as a function of diagnosis and ovulation protocol utilizing an extended semen transport time. This allowed clients to conveniently collect IUI specimens in the comfort and privacy of their home. A single IUI per treatment cycle was performed. BASIC PROCEDURES: Three-hundred-ten consecutive infertilty couples having unexplained, male factor, ovulatory dysfunction, endometriosis, tubal factor or combined diagnostic factors receiving a total of 584 cycles of IUI were included. Ovulation protocols included LH surge, clomiphene citrate (CC)-hCG, CC-gonadotropins(Gn)-hCG, Gn-hCG or leuprolide acetate (L)-Gn-hCG followed 36-42 hours by a single IUI. Pregnancy rates per cycle (fecundity) and per couple (fertility) as a function of diagnosis, ovulation protocol and cycle number were evaluated. In each cycle the couples processed the specimen by adding sperm washing medium at room temperature to the specimen 30 min following collection and allowed it to incubate for two hours prior to IUI during transport. MAIN FINDINGS: Overall, fecundity was 11.8% (69/584) and fertility was 22.3% (69/310); respectively by diagnosis was: unexplained 22.6%, 38.8%; male factor 18.8%, 42.9%; ovulatory dysfunction 12.4, 22.6%; endometriosis 5.3%, 11.1%; tubal factor 7.6%,13.3%; and combined factors 9.7%, 20.0%. Unexplained vs endometriosis (P < 0.0001, P < 0.005), tubal factor (fecundity P < 0.008) and ovulatory dysfunction (fecundity P < 0.027) was statistically different. Male factor vs endometriosis (P < 0.011, P < 0.036) was significantly different. Ovulatory dysfunction vs endometriosis was significantly different (fecundity P < 0.027). Pregnancies by ovulation protocol: LH surge 4.5%,10.5%; CC-hCG 9.4%,14.9%; CC-Gn-hCG 13.7%, 23.7%; Gn-hCG 17.5%, 45.3%; L-Gn-hCG 3.5%, 6.7%. For Gn-hCG vs L-Gn-hCG (P < 0.009, P < 0.030) and LH surge (fecundity P < 0.033). CC-Gn-hCG vs CC-hCG (fertility P < 0.050) and L-Gn-hCG (P < 0.033, P < 0.034). Gn-hCG vs CC-hCG (fecundity P < 0.043). CONCLUSIONS: We conclude that IUI is effective when utilizing an extended transport time allowing most couples to collect the specimen at home and is most effective when utilizing Gn-hCG therapy. Based on our analysis, endometriosis, tubal factor and combined diagnostic categories should proceed earlier to higher level assisted reproductive technologies.

Serum antiendometrial antibodies and diagnosis of endometriosis.

PROBLEM: The purpose of the present prospective multi-center study is to investigate the relationship between laparoscopic diagnosis of endometriosis and results of a serum antiendometrial antibody (AEA) assay. METHOD OF STUDY: Indirect immunofluorescence detection of AEA was performed on serum specimens from patients presenting with dysmenorrhea or chronic pelvic pain and infertility (n = 2609) utilizing frozen sections of endometrium acquired on cycle days 18-21 from normally cycling women without endometriosis. Diagnostic laparoscopy was performed within 1 year of AEA assay on 527 tested women. RESULTS: The relationship between the serum AEA and laparoscopic verification was characterized by a positive predictive value = 88%, negative predictive value = 86%, sensitivity = 87% and specificity = 87%. CONCLUSION: The AEA assay is a very good screening test for patients suspected of having endometriosis and should be utilized prior to laparoscopy in diagnostic categories of dysmenorrhea or chronic pelvic pain and infertility.

Percutaneous laser disc decompression for the treatment of discogenic lumbar pain and sciatica: a preliminary report with 3-month follow-up in a general pain clinic population.

OBJECTIVE: Our aim was to evaluate the short-term efficacy of percutaneous laser disc decompression (PLDD) for the treatment of lumbar discogenic pain and sciatica. BACKGROUND DATA: PLDD has been reported to be a safe, effective, minimally invasive treatment option for patients with lumbar spinal pain associated with herniated disc, as an alternative to open spinal surgery. The present study was designed to evaluate the effectiveness of the procedure in patients attending a comprehensive interventional pain management clinic. MATERIALS AND METHODS: Thirty-two consecutive patients with discogenic lumbar spinal pain with or without sciatica were identified by MRI scanning and discography. Patients with symptoms attributable to a herniated or degenerated lumbar disc were treated with PLDD utilizing the neodymium-YAG laser. The primary endpoint of the study was the standardized symptom score on the American Academy of Orthopedic Surgery (AAOS) Outcomes Assessment Questionnaire for neurogenic and back pain symptoms at pre-treatment baseline, and at 3 months after laser treatment. RESULTS: Of the 30 patients with sciatica at baseline, 24 (80%) reported improvement in sciatica symptoms at three months, with a mean improvement of 68% (p = 0.001 from baseline values). Of the 32 patients with discogenic pain at baseline, 24 (75%) reported improvement at 3 months, with a mean improvement of 44% (p = 0.0005 from baseline values). No instances of infection, nerve injury, or clinically significant bleeding were identified during the 3-month follow-up period. Similar results were also seen in seven patients undergoing PLDD for residual back pain and sciatica following open spinal surgery. Sixty-three percent of patients complained of new-onset or worsening of mechanical low back pain following PLDD, thought to be related to the procedure. Back pain was considered mild to moderate and was self-limited, or responsive to analgesics and lumbar facet block with or without lumbar rhizotemy. CONCLUSION: PLDD with the neodymium-YAG laser is a safe and effective treatment for discogenic lumbar pain and sciatica during a preliminary 3-month follow-up period in a general pain management practice setting. Post-procedural mechanical low back pain is common and easily treated without sequellae. No instances of infection, neural injury, or other serious complications were observed.

Fast-tracking pulmonary resections.

OBJECTIVE: We streamlined our care after pulmonary resection for quality and cost-effectiveness. METHODS: A single surgeon performed 500 consecutive pulmonary resections through a thoracotomy over a 2(3/4)-year period in a university setting. Patients were extubated in the operating room and sent directly to their hospital room. Chest tubes were placed to water seal and removed on postoperative day 2 if there was no air leak and drainage was less then 400 mL/d. Epidural catheters were used and removed by postoperative day 2. The plan for each day and discharge on postoperative day 3 or 4 was reviewed with the patients and families daily during rounds. The patient went home the day the last chest tube was removed. Persistent air leaks were treated with Heimlich valves. RESULTS: There were 500 patients (338 men), with a median age of 58 years (range, 3-87 years). Of these patients, 293 had pre-existing conditions. Seventy-three (15%) patients had been denied operations by at least one other surgeon. Four hundred nineteen (84%) patients had successful placement of a functioning preoperative epidural catheter. Pneumonectomy was performed in 32 (6%) patients, segmentectomy was performed in 16 (3%) patients, and lobectomy, sleeve lobectomy, and/or bilobectomy was performed in 194 (39%) patients. Nonanatomic resections were performed for metastasectomy. This included a single wedge resection in 161 (32%) patients and multiple wedge resections in 97 (19%) patients. A total of 482 (96%) patients were extubated in the operating room, and 380 (76%) patients were sent to their hospital room. The remaining 120 patients went to the intensive care unit for a median of 1 day (range, 1-41 days). Complications occurred in 107 (21%) patients, and operative mortality was 2.0%. Median day of discharge was postoperative day 4 (range, 2-119 days). A total of 327 (65%) patients left the hospital on postoperative day 4 or sooner. By survey, 97% of patients had excellent or good satisfaction with their care at hospital discharge, and 91% were extremely happy or satisfied at the 2-week follow-up contact. CONCLUSIONS: Most patients who undergo elective pulmonary resection can be extubated immediately after the operation, go directly to their room and avoid the intensive care unit, be discharged on postoperative day 3 or 4, and have minimal morbidity and mortality with high satisfaction both at discharge and at the 2-week follow-up contact. Techniques that seem to accomplish this include the following: the use of a water seal, removal of epidural catheters on postoperative day 2, early chest tube management, treatment of persistent air leaks with Heimlich valves, and daily reinforcement of the planned events for each day, as well as on the date of discharge with the patients and their families.

Fas expression prevents cholangiocarcinoma tumor growth.

Cholangiocarcinoma continues to have a dismal prognosis with an overall survival rate of less than 10%. An increased understanding of the molecular oncogenesis of this tumor is needed. Fas/APO-1 (CD95) receptor and Fas ligand have been implicated as key factors in apoptosis. In this study we have examined the role of the Fas receptor in the growth of cholangiocarcinoma. The purpose of this study was to evaluate the role of the Fas receptor in the induction of apoptosis in cholangiocarcinoma and to assess the role of the Fas receptor in cholangiocarcinoma tumorigenesis. Human cholangiocarcinoma cells, SK-ChA-1, were evaluated for Fas receptor expression using fluorescence-activated cell sorting (FACS). Distinct cell populations (Fas-positive and Fas-negative) were isolated by FACS and cloned from single cell dilutions. Fas expression was assessed by FACS and reverse transcriptase-polymerase chain reaction (RT-PCR). Cell populations were further characterized by their sensitivity to anti-Fas monoclonal antibody at 72 hours. Cell viability and apoptotic index were evaluated by trypan blue cell count and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) assay, respectively. Distinct cell populations were evaluated for their ability to form tumors in BALB/c nude mice (2.5 x 10(6) cells per subcutaneous injection). After 4 weeks, tumors were evaluated for tumor area by caliper measurement and Fas expression by RT-PCR. Maintenance of biliary phenotype was assured by means of AE-1 (cytokeratin) immunohistochemistry. Populations of Fas-positive and Fas-negative cells were identified, isolated, and confirmed by FACS and RT-PCR. Treatment of Fas-positive cells with anti-Fas monoclonal antibody produced an 80% reduction in cell viability compared to no decrease in viability in Fas-negative cells by trypan blue cell count. TUNEL staining showed an apoptotic index of 75% for Fas-positive cells incubated with anti-Fas monoclonal antibody and no significant evidence of apoptosis in the Fas-negative cells. When cholangiocarcinoma cells were subcutaneously injected into nude mice, only Fas-negative cells formed tumor nodules; Fas-positive cells failed to form tumor nodules. The analyzed tumors lacked Fas messenger RNA by RT-PCR but maintained the biliary cytokeratin AE-1 by immunohistochemistry. Fas receptor expression is an important mediator of apoptosis in cultured human cholangiocarcinoma cells and appears to be a critical determinant of cholangiocarcinoma tumor growth in nude mice.

Apoptosis and tumorigenesis in human cholangiocarcinoma cells. Involvement of Fas/APO-1 (CD95) and calmodulin.

We have previously demonstrated that tamoxifen inhibits the growth of human cholangiocarcinoma cells in culture and inhibits tumor growth when cells are injected into nude mice. However, the mechanism of action of tamoxifen remains unknown. Here we demonstrate that tamoxifen and trifluoperazine, both potent calmodulin antagonists, induce apoptosis in vitro, probably acting via the Fas system, in human cholangiocarcinoma cells. Human cholangiocarcinoma cell lines heterogeneously express Fas antigen on their surface. Fas-negative and Fas-positive surface-expressing cells were isolated, cloned, and cultured. Fas antibody, tamoxifen, and trifluoperazine induced dose-dependent apoptosis only in Fas-positive cells; Fas-negative cells were unaffected. Furthermore, apoptosis induced by tamoxifen in Fas-positive cells was blocked by an inhibitory Fas antibody. Tamoxifen was not acting through an anti-estrogenic mechanism, because neither Fas-negative nor Fas-positive cells expressed estrogen receptors and the pure anti-estrogen compound, ICI 182780, did not induce apoptosis in either cell line. Fas-negative cells, but not Fas-positive cells, were able to produce tumors when subcutaneously injected into nude mice. These findings suggest Fas may be a candidate oncogene involved in the pathogenesis of cholangiocarcinoma. Furthermore, the similarity between the pro-apoptotic effects of tamoxifen and trifluoperazine support an underlying molecular mechanism for Fas-mediated apoptosis that involves calmodulin.

An unusual etiology of biliary hilar obstruction and the potential role of acidic fibroblast growth factor in the development of a biliary neuroma.

Neuroma of the biliary tract is a rare condition thought to be caused by trauma secondary to cholecystectomy. More rare is the occurrence that causes symptomatic biliary obstruction. A 65-year-old woman was hospitalized because of abdominal pain, nausea, vomiting, and general malaise of 1 to 2 months duration. Cholecystectomy had been performed 40 years before. Ultrasound revealed hepatomegaly and dilated intrahepatic ducts. CT showed intra- and extrahepatic ductal dilatation with questionable intraductal mass. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography demonstrated stricture of the hepatic duct bifurcation. The biliary bifurcation was resected, and hepaticojejunostomy was performed. The patient's postoperative course was unremarkable. Histological examination of the surgical specimen revealed positive staining for the S-100 antigen of the obstructing luminal stricture (without evidence of cholangiocarcinoma), which was consistent with a biliary neuroma. Positive staining was also found for acidic (and not basic) fibroblast growth factor (FGF) and two of its high affinity receptors (FGFR-1 and FGFR-4). This study supports the apparent association between biliary neuromas and cholecystectomy as well as the potential role of an established angiogenic and neurogenic growth factor in the formation of this tumor. Finally, this case is also unique in that it represents the longest interval between cholecystectomy and presentation of a biliary neuroma, 40 years after surgery.

Neurobehavioral symptoms and family functioning in traumatically brain-injured adults.

Traumatic brain injury (TBI) often results in a myriad of symptoms across physical, cognitive, and neurobehavioral domains. Despite inherent limitations associated with physical or cognitive impairments, the extant literature suggests that neurobehavioral symptoms tend to be the most distressing symptoms for the family and are more strongly related to poor outcome for the patient. The Neuropsychology Behavior and Affect Profile (NBAP) along with the General Functioning subscale of the Family Assessment Device (FAD-GF) and the Perceived Stress Scale were administered to 153 family members of persons who had sustained a TBI. The results provide new normative data and statistical support for the NBAP as a promising measure of neurobehavioral symptomatology following TBI. The correlation of.54 (p <.01) between FAD-GF and Full Scale NBAP scores provides powerful support for the hypothesis that family dysfunction is related to the presence of neurobehavioral symptoms in the patient. NBAP domains of Depression, Inappropriateness, Pragnosia, and Indifference appear most strongly related to family functioning and also bear a significant relationship to caregiver stress level and patient unemployment, whereas injury severity had little impact on either family functioning or neurobehavioral symptoms. The findings reinforce the significance of neurobehavioral symptoms and fortify their proposed link to family dysfunction post-TBI.

Intramural pregnancy with fetal survival: case history and discussion of etiologic factors.

Intramural implantation is among the rarest sites for ectopic pregnancy. The first intramural pregnancy with fetal survival is described and the possible etiologic role of prior uterine surgery is discussed.