Extensive haplotype diversity in African American mothers and their cord blood units.

HLA-A, -B, -C, -DRB1, -DQB1 assignments were obtained for 374 pairs of African American mothers and their umbilical cord blood units (CBU) by DNA sequencing. An algorithm developed by the National Marrow Donor Program was used to assign 1122 haplotypes by segregation. Seventy percent of the haplotypes carried assignments at all five loci. In the remainder, alleles at various loci, most often DQB1 in 48% of the haplotypes with a missing assignment, could not be assigned due to sharing of both alleles by mother and CBU. There were 652 haplotypes carrying a unique combination of alleles at the five loci; the majority (74%) were singletons. Novel B∼C and DRB1~DQB1 associations were observed. The results show the genetic diversity in this population and provide validation for a publically available tool for pedigree analysis. Our observations underscore the need for procurement of increased numbers of units in the national cord blood inventory in order to identify matching donors for all patients requiring hematopoietic stem cell transplantation.

Prosthetic mesh contamination during NOTES(®) transgastric hernia repair: a randomized controlled trial with swine explants.

PURPOSE: Natural Orifice Translumenal Endoscopic Surgery (NOTES(®)) is a developing field in minimally invasive surgery that has been applied across a wide range of procedures; however, infectious concerns remain. Most of the applications have been for extraction, rather than reconstructive procedures. Prosthetic hernia repair, is a constructive procedure, has the unique challenge of avoiding contamination and infection of a permanent implant. Utilizing a novel device, we hypothesize that we can significantly reduce or eliminate prosthetic contamination during a transgastric approach for delivery of a clinically relevant, permanent, synthetic prosthetic. METHODS: 20 swine explants of stomach with attached esophagus were prepared by placing an ultraviolet (UV) light sensitive gel within the lumen of the stomach. Each stomach then underwent endoscopic gastrotomy utilizing a needle, wire guide, and 18-mm balloon dilator. A 10 × 15 cm polypropylene prosthetic was rolled and tied with a 2-0 silk suture, and delivered with one of two methods. Group A (control) utilized a snare to grasp the prosthetic adjacent to the endoscope, which was used to drag it through the gastrotomy. Group B (device) utilized a modified esophageal stent delivery system to deliver the prosthetic through the gastrotomy. Each prosthetic was then digitally photographed with UV illumination, with the contaminated areas illuminating brightly. Software analysis was performed on the photographs to quantify areas of contamination for each group. Statistical analysis was performed using a two-tailed t test with unequal variance. RESULTS: Group A demonstrated a mean of 57 % of the surface area of the prosthetic contaminated with UV light sensitive gel. Group B (experimental group) showed a mean of 0.01 % of the surface area contaminated (p < 0.0001). 95 % confidence intervals indicated that the unprotected delivery technique exposes approximately 6,000 times more of the surface area to contamination than the delivery device. CONCLUSION: Use of this modified stent delivery system can nearly eliminate prosthetic contamination when placed via a transgastric approach in a swine explants model. Theoretically, the reduced inoculum size would reduce or eliminate clinical infection. Since the inoculum size required for clinical prosthetic infection for intraperitoneal mesh is unknown, further study is warranted to test the ability to eliminate clinical infection related to prosthetic delivery with this technique.

NOTES transgastric abdominal wall hernia repair in a porcine model.

INTRODUCTION: With approximately 1 million ventral and inguinal hernia repairs performed in the United States each year, even small rates of complications translate into large numbers of patients. Less invasive approaches that potentially lower morbidity deserve consideration, recognizing there are many technical considerations that currently limit their use. We describe a reproducible technique and lessons learned in our laboratory that answer some existing questions with regards to the use of NOTES for hernia repair. METHODS: A non-survival porcine model with general anesthesia was utilized in all cases. Each animal underwent transgastric peritoneal access with a percutaneous endoscopic gastrostomy (PEG) technique, and the gastrotomy was dilated with a wire-guided balloon dilatation catheter. An Esophageal Z-stent delivery device (Cook Medical, Winston-Salem, NC) was modified ex-vivo to allow us to introduce and protect a 10 x 15 cm lightweight polypropylene hernia prosthetic with pre-placed sutures. Once deployed, the sutures were pulled through the abdominal wall using a looped spinal needle technique in combination with the flexible endoscope. After the four anchoring sutures were tied, proprietary endoscopically placed tacks (Cook Medical) were placed at regular intervals between the sutures to secure the edges of the prosthetic. RESULTS: Hernia repairs were performed on five animals. In each case, we successfully completed prosthetic delivery and deployment into the peritoneal cavity, anchoring to the abdominal wall with full-thickness abdominal wall sutures, and endoscopically placed nitinol tacks. All prosthetics were deployed flat against the anterior abdominal wall. Operative times ranged from 65 to 120 min. CONCLUSION: Transgastric abdominal wall hernia repair is feasible, consistent, and reproducible. In particular, the delivery system can successfully deliver the prosthetic across the gastric wall via a transoral route. Survival animal experiments investigating outcomes related to quality of repair, microbiology, adhesions, and visceral closure need to be done. Human studies are not recommended until these issues are formally investigated.

Natural orifice transluminal endoscopic surgery gastrotomy closure in porcine explants with the Padlock-G clip using the Lock-It system.

BACKGROUND AND STUDY AIMS: The success of transgastric surgery depends on reliable, secure closure of the gastrotomy. Few tests of the integrity of these closures have been published. This study aimed to determine whether a gastrotomy suitable for a NOTES procedure can be closed safely and effectively from within the stomach using a novel endoscopically placed device, the Padlock-G with the Lock-It delivery system. METHODS: In a series of eight consecutive porcine gastric explants gastrotomy was performed in an ex vivo animal laboratory, the gastrotomy being closed with the Padlock-G followed by burst pressure testing after completion of the procedure. Gastrotomies were made in porcine explants. T-tags were placed on either side of the gastrotomy, and, with the T-tags pulled into an endoscopic cap, the Padlock-G was deployed. Gastric transmural pressure gradients at bursting of these closures were measured during insufflation of the explanted stomachs with a high-pressure insufflator. RESULTS: The mean burst pressure of the gastrotomy closures was 68.0 mm Hg (range: 45 - 107 mm Hg). All of the stomachs ultimately ruptured at the closure sites, with the exception of the stomach that ruptured at the highest value (107 mm Hg), which ruptured at a site approximately 5 cm away from the closure site. All of the closures were accomplished in 30 minutes or less. CONCLUSIONS: The Padlock-G clip provides a secure gastric closure for natural-orifice surgery.

The role of diagnostic laparoscopy for chronic abdominal conditions: an evidence-based review.

BACKGROUND: Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of intraabdominal diseases. The aim of this review is a critical examination of the available literature on the role of laparoscopy for chronic intraabdominal conditions. METHODS: A systematic literature search of English-language articles on MEDLINE, the Cochrane database of evidence-based reviews, and the Database of Abstracts of Reviews of Effects was performed for the period 1995-2006. The level of evidence in the identified articles was graded. The search identified and reviewed six main categories that have received attention in the literature: pelvic pain and endometriosis, primary and secondary infertility, nonpalpable testis, and liver disease. RESULTS: The indications, contraindications, risks, benefits, diagnostic accuracy of the procedure, and its associated morbidity are discussed. CONCLUSIONS: The limitations of the available literature are highlighted, and evidence-based recommendations for the use of laparoscopy to stage intraabdominal cancers are provided.

The role of staging laparoscopy for intraabdominal cancers: an evidence-based review.

Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of intraabdominal diseases. The aim of this review is a critical examination of the available literature on the role of laparoscopy for the staging of intraabdominal cancers. A systematic literature search of English-language articles on MEDLINE, the Cochrane database of evidence-based reviews, and the Database of Abstracts of Reviews of Effects was performed for the period 1995-2006. The level of evidence in the identified articles was graded. The search identified and reviewed seven main categories that have received attention in the literature: esophageal cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, biliary tract cancer, colorectal cancer, and lymphoma. The indications, contraindications, risks, benefits, diagnostic accuracy of the procedure, and its associated morbidity are discussed. The limitations of the available literature are highlighted, and evidence-based recommendations for the use of laparoscopy to stage intraabdominal cancers are provided.

Laparoscopic resection of curable colon and rectal cancer: an evidence-based review.

The initial enthusiastic application of laparoscopic techniques to colorectal surgical procedures was tempered in the early 1990s by reports of tumor implants in the laparoscopic incisions. Substantial evidence has accumulated, including evidence from randomized controlled trials, to support that laparoscopic resection results in oncologic outcomes similar to open resection, when performed by well-trained, experienced surgeons. This review was developed in conjunction with guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons. Data from the surgical literature concerning laparoscopic resection of curable colorectal cancer was evaluated regarding diagnostic evaluation, preoperative preparation, operative techniques, prevention of tumor implants, and training and experience. Recommendations are accompanied by an assessment of the level of supporting evidence available at the time of the development of the guidelines.

Performance and ergonomic characteristics of expert surgeons using a face-mounted display during virtual reality-simulated laparoscopic surgery: an electromyographically based study.

BACKGROUND: Display positions for laparoscopy in current operating rooms may not be optimal for surgeon comfort or task performance, and face-mounted displays (FMDs) have been forwarded as a potential ergonomic solution. Little is known concerning expert use characteristics of these devices that might help define their role in future surgical care. The authors report the performance and ergonomic characterization of an FMD using virtual reality simulation technology to recreate the surgical environment. METHODS: An FMD was studied in short- and long-duration trials of validated virtual reality-simulated surgical tasks. For the short-duration phase 7, expert surgeons were familiarized with a task on a conventional monitor, then returned on two separate occasions to repeat the task with the FMD while digital photos were taken during task performance and at the end in a standardized fashion. For the long-duration phase 5, expert surgeons performed two separate trials with repetitive groups of validated tasks for a minimum of 30 min while electromyelogram and performance data were measured. Photos of their gaze angle during and at the end of the trial were taken. RESULTS: All the participants consistently assumed a gaze angle slightly below horizontal during task performance. Performance scores on the FMD did not differ from those obtained with a conventional display, and remained stable with repetitive task performance. No participant had electromyelogram signals that exceeded the established thresholds for fatigue, but some had values within the threshold range. CONCLUSION: The natural gaze angle during simulated surgery was consistently a bit below horizontal during rigorous virtual reality-simulated tasks. Performance was not compromised during expert surgeons' use of an FMD, nor did muscle fatigue characteristics arise under these conditions. The findings suggest that these devices may represent a viable alternative to conventional displays for minimally invasive surgery, but definition of specific roles requires further investigation.

Laparoscopic versus open incisional hernia repair: a single-institution analysis of hospital resource utilization for 884 consecutive cases.

BACKGROUND: To analyze hospital resource utilization for laparoscopic vs open incisional hernia repair including the postoperative period. METHODS: Prospectively collected administrative data for incisional hernia repairs were examined. A total of 884 incisional hernia repairs were examined for trends in type of approach over time. Starting October 2001, detailed records were available, and examined for operating room (OR) time, cost data, length of stay (LOS), and 30-day postoperative hospital encounters. RESULTS: Of the total, 469 incisional hernias were approached laparoscopically (53%) and 415 open (47%). Laparoscopic repair had shorter LOS (1 +/- 0.2 days vs 2 +/- 0.6 days), longer OR time (149 +/- 4 min vs 89 +/- 4 min), higher supply costs (2,237 dollars +/- 71 dollars vs 664 dollars +/- 113 dollars), slightly lower total hospital cost (6,396 dollars +/- 477 dollars vs 7,197 dollars +/- 1,819 dollars), and slightly more postoperative hospital encounters (15% vs 13%). Use of laparoscopy increased over time (37% in 2000 vs 68% in 2004). CONCLUSIONS: Laparoscopic incisional hernia repair is becoming increasingly popular, and not at increased cost to the health care system.

Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response.

OBJECTIVES: To evaluate the safety and pharmacodynamic effect of co-administration of subtherapeutic doses of PT-141, a cyclic heptapeptide melanocortin analogue, and sildenafil to patients with erectile dysfunction. METHODS: Nineteen patients with erectile dysfunction who were responders to either Viagra or Levitra by self-report were given 25 mg sildenafil and 7.5 mg intranasal PT-141, 25 mg sildenafil and an intranasal placebo spray, and a placebo tablet and an intranasal placebo spray in a randomized cross-over design. Erectile activity in response to two 30-minute episodes of visual sexual stimulation was assessed by RigiScan during a 6-hour postdose period. RESULTS: The erectile response induced by co-administration of PT-141 and sildenafil was significantly greater than the response elicited by administration of sildenafil alone. Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy. CONCLUSIONS: Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated.

Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra.

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following subcutaneous administration to healthy male subjects and to patients with erectile dysfunction (ED) who report an inadequate response to Viagra. An inadequate response was defined for this study by patient report indicating that achievement of an erection suitable for vaginal penetration occurred < or =50% of the time while taking 100 mg Viagra. Erectile responses were assessed by RigiScan in healthy subjects in the absence of visual sexual stimulation (VSS) and in ED patients in the presence of VSS. Doses ranging from 0.3 to 10 mg were administered to healthy male subjects, resulting in a statistically significant erectile response at doses greater than 1.0 mg. ED patients were treated with placebo, 4 or 6 mg PT-141 in a crossover design in the presence of VSS. The erectile response induced by PT-141 was statistically significant at both doses. PT-141 was safe and well tolerated in both studies. The erectogenic potential of PT-141, its tolerability profile and its ability to cause significant erections in patients who do not have an adequate response to a PDE5 inhibitor suggest that PT-141 may provide an alternative treatment for ED with a potentially broad patient base.

Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction.

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.

PT-141: a melanocortin agonist for the treatment of sexual dysfunction.

PT-141, a synthetic peptide analogue of alpha-MSH, is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Administration of PT-141 to rats and nonhuman primates results in penile erections. Systemic administration of PT-141 to rats activates neurons in the hypothalamus as shown by an increase in c-Fos immunoreactivity. Neurons in the same region of the central nervous system take up pseudorabies virus injected into the corpus cavernosum of the rat penis. Administration of PT-141 to normal men and to patients with erectile dysfunction resulted in a rapid dose-dependent increase in erectile activity. The results suggest that PT-141 holds promise as a new treatment for sexual dysfunction.

Broccoli plants with pyramided cry1Ac and cry1C Bt genes control diamondback moths resistant to Cry1A and Cry1C proteins.

This study was undertaken to determine the effects of pyramiding two Bacillus thuringiensis (Bt) genes in the same plant on the production of Bt proteins and the control of diamondback moths (DBM, Plutella xylostella) resistant to one or the other protein. Broccoli lines carrying both cry1Ac and cry1C Bt genes were produced by sexual crosses of cry1Ac- and cry1C-transgenic plants. Plants containing both genes were selected by tests for resistance to kanamycin and hygromycin, and confirmed by PCR analysis for the Bt genes. Both cry1Ac and cry1C mRNAs were detected in the hybrid lines, and Cry1Ac and Cry1C proteins were stably produced at levels comparable to the parental plants. Plants producing both Cry1Ac and Cry1C proteins caused rapid and complete mortality of DBM larvae resistant to Cry1A or Cry1C, and suffered little or no leaf damage. These plants, in combination with the resistant DBM populations available, will allow greenhouse or field studies of resistance management strategies involving gene pyramiding.

Gas extravasation complicating laparoscopic extraperitoneal inguinal hernia repair.

Carbon dioxide can extravasate from the abdominal cavity during insufflation and result in pneumomediastinum, pneumothorax, and subcutaneous emphysema. We report a case of unilateral pneumothorax with pneumomediastinum and subcutaneous emphysema after laparoscopic extraperitoneal bilateral inguinal hernia repair. Additionally, we discuss the pathophysiology, diagnostic work-up, and management of this malady. Because of the natural resolution of CO2 pneumothoraces, observation for asymptomatic patients is appropriate, whereas tube thoracostomy should be reserved for symptomatic patients. It is utmost importance to determine the etiology of gas extravastion and consider other complications such as airway or esophageal injury or pulmonary barotrauma.

Slope and the Zöllner illusion.

Informal observation suggests that the magnitude of the Zöllner illusion is reduced when the figure is viewed on a sloping plane. The hypothesis that this effect derives from the enlargement of the acute angle of intersection between the obliques and the verticals in the figure when it is viewed on a sloping plane is here investigated. The magnitude of the Zöllner illusion was measured with the use of a visual analogue scale. The results show that the change in the magnitude of the Zöllner effect as a function of the slope of the figure is different from that for corresponding figures, with enlarged angles of intersection between the obliques and the verticals, presented vertically. It is concluded that the enlargement of the angles of intersection can only partly account for the reduction of the Zöllner effect when the figure is viewed under slope, and that some other factor must be involved. An alternative hypothesis is evaluated whereby the effects result from the diminution in the contrast of the obliques when the figure is viewed under slope. Data are also presented to show that observers are able to perceive the enlarged or foreshortened angles of intersection veridically.

A simple and inexpensive technique for closing trocar sites and grasping sutures.

Grasping sutures during laparoscopic surgery is useful in closing trocar sites, repairing ventral hernias, and securing abdominal wall bleeding. This can be a cumbersome task through small incisions. An 18 gauge spinal needle and the suture of choice for accomplishing the job at hand can be used with a laparoscopic-assisted technique that is simple, inexpensive, and easy to learn. Surgeons performing laparoscopy should add this technique to their repertoire.

Glass patterns: grouping by contrast similarity.

Recent work has shown that certain contrast phenomena associated with Glass patterns can be accounted for by filtering mechanisms applied within the luminance or energy domain. Hitherto, these phenomena were regarded as problematic for energy-processing models, and were taken as evidence in support of symbolic-processing accounts. An additional, and controversial, contrast effect is investigated. It is shown that in a Glass pattern consisting of simultaneous vertical and horizontal translations of different contrast strength, the most salient structure is determined by grouping (pairing) of the two low-contrast elements of the pattern. The finding that grouping in such patterns is by contrast similarity, as opposed to energy, is consistent with the symbolic-processing approach, but has yet to be accounted for by filtering mechanisms.

The McCollough effect in pigeons: tests of persistence and spatial-frequency specificity.

Eight pigeons were trained on a conditional discrimination using red and green saturated and desaturated fields, and red and green saturated and desaturated vertical and horizontal black-on-colour gratings. The pigeons learned to discriminate the stimuli on the basis of colour, to a high level of accuracy, regardless of saturation or the presence of gratings. The pigeons were then repeatedly exposed to stimuli in which colour and grating orientation were correlated, following which they were tested for the presence of the McCollough orientation-contingent colour after-effect, using black-on-white vertical and horizontal gratings. Six of the birds showed convincing evidence of the presence of the McCollough effect, and the effect was significant across all birds. These findings support those of Roberts (1984), using a substantially different methodology. The six birds showing the McCollough effect were then tested for the persistence of the effect at delays of 24 to 96 h. Four of the birds showed evidence of the McCollough effect at least 24 h after the induction procedure. Three of these birds were also tested to investigate the spatial frequency selectivity of the effect. The results suggest a narrow tuning of the McCollough effect in pigeons of less than 0.36 log units.