Clinical Focus

  • da Vinci Surgery
  • Robotic Surgery
  • Urology
  • Pediatric Urology
  • Laparoscopic Surgery

Academic Appointments

Administrative Appointments

  • Director, Minimally Invasive Surgery Program, Pediatric Urology Clinic, Lucile Packard Children's Hospital (2010 - Present)
  • Director, Prenatal Program, Pediatric Urology Clinic, Lucile Packard Children's Hospital (2010 - Present)
  • Head, Chronic Infection Working Group, Institute of Immunity, Transplantation, and Infection (2009 - Present)
  • Member, Care Improvement Committee, Lucile Salter Packard Children's Hospital at Stanford (2009 - 2012)

Honors & Awards

  • Recognized Doctor, Healthgrades Honor Roll (2013-)
  • Physician, Best Doctors in America (2013-)
  • Stinehart-Reed Award (co-investigator), Stanford Stem Cell Institute (2011-2012)
  • Optimus Foundation Global Health Research Innovation Program, UBS (2011)
  • C-IDEA Scholar, Stanford Consortium for Innovation, Design, Evaluation and Action (C-IDEA) (2011-2012)
  • Center for Clinical Human Immunology Pilot Project Grant, Stanford CCHI (2011)
  • 1st Runner-Up, Best Basic Science Abstract, American Academy of Pediatrics, Section of Urology (2010)
  • Translational Science Development Cancer Research Award, Stanford Cancer Center (2010)
  • Mentored Clinical Scientist Award, NIH/NIDDK (2010-2015)
  • Pilot Early Career Award, Stanford Pediatric Research Fund, Spectrum Child Health Research (2010 and 2011)
  • Seed Funding for Imaging Research or Educational Projects, Center for Biomedical Imaging at Stanford (CBIS) (2010)
  • Recognition of Service Excellence (R.O.S.E.) Award, Lucile Packard Children's Hospital (2010)
  • Exchange Fellowship, European Society of Pediatric Urology-American Academy of Pediatrics (2009)
  • Research Award, Society of Pediatric Urology (2008)
  • Ambrose/Reed Gyrus ACMI Socioeconomics Prize Essay Contest, American Urological Association (2008)
  • Travel Fellowship, Urologic Diseases in America Symposium (2008)
  • 1st place, Basic Science Section, Northern California Urology Resident Research Symposium (2006)
  • Winner, Earl F. Nation Resident Scholarship Award, UCSF, Western Section, American Urological Association (2006)
  • 2nd place, Miley B. Wesson/Gyrus ACMI Resident Essay Contest, Western Section, American Urological Association (2006)
  • Finalist, Best Basic Science Poster, American Academy of Pediatrics, Urology Section (2006)
  • Ambrose/Reed Gyrus ACMI Socioeconomics Prize Essay Contest, American Urological Association (2006)
  • 3rd place, Basic Science Section, Northern California Urology Resident Research Symposium (2005)
  • Finalist, Best Basic Science Poster, American Academy of Pediatrics, Urology Section (2004)
  • THANKS Star Award, University of California San Francisco (2002)
  • Ernest McCulloch and James Till Award, American Society of Blood and Marrow Transplantation (2001)
  • Alumni Thesis Award, Thomas Jefferson University Alumni Association (2001)
  • The Hyman Menduke Research Prize, Jefferson Medical College (2001)
  • The Robert J. Mandle Memorial Graduation Award, Jefferson Medical College (2001)
  • Alumni Travel Fellowship, Thomas Jefferson University (1999)
  • William Potter Student Research Prize, Sigma Xi (1999)
  • Benjamin and Ray Sonnenfeld Memorial Research Fund, American Heart Association (1996)
  • Medical Student Research Fellowship, Alpha Omega Alpha (1995)

Professional Education

  • Fellowship:Texas Children's Hospital Baylor College of Medicine (2009) TX
  • Professional Education:Thomas Jefferson University/AI duPont Hospital (2001) DE
  • Medical Education:Thomas Jefferson University/AI duPont Hospital (2001) DE
  • Board Certification: Urology, American Board of Urology (2012)
  • Board Certification: Pediatric Urology, American Board of Urology (2012)
  • Residency:UCSF (2007) CA
  • Residency:UCSF (2003) CA
  • Fellowship, Texas Children's Hospital, Pediatric Urology (2009)
  • Residency, UCSF, Urology (2007)
  • Ph.D., Thomas Jefferson University, Immunology (2001)
  • M.D., Thomas Jefferson University, Medicine (2001)
  • B.S., Stanford University, Biology (1993)

Community and International Work

  • International medical missions (pediatric urology)


    pediatric urology

    Partnering Organization(s)

    International Volunteers in Urology and Medicine (IVUmed)

    Populations Served

    Mongolia, Cameroon, Iran, Tanzania, Kenya, Vietnam, Senegal, Mozambique



    Ongoing Project


    Opportunities for Student Involvement


  • Models of urinary schistosomiasis, Stanford campus


    Schistosoma haematobium

    Partnering Organization(s)

    International Health at Stanford, Global Health at Stanford

    Populations Served

    Portions of the Middle East and sub-Saharan Africa


    Bay Area

    Ongoing Project


    Opportunities for Student Involvement


Research & Scholarship

Current Research and Scholarly Interests

Our laboratory is interested in how microbial-triggered inflammation protects against pathogens and yet can paradoxically harm the host through secondary effects such as tissue fibrosis and carcinogenesis. The genitourinary tract is our model system. We are examining anti-pathogenic inflammation induced by uropathogenic E. coli. Chronic infection-mediated tissue fibrosis and carcinogenesis are being studied using models of Schistosoma haematobium. Through our research, we seek to better understand microbial-triggered inflammation and harness its potential for human benefit.


2013-14 Courses

Postdoctoral Advisees

Graduate and Fellowship Programs


Journal Articles

  • Effects of robotic manipulators on movements of novices and surgeons. Surgical endoscopy Nisky, I., Okamura, A. M., Hsieh, M. H. 2014


    Robot-assisted surgery is widely adopted for many procedures but has not realized its full potential to date. Based on human motor control theories, the authors hypothesized that the dynamics of the master manipulators impose challenges on the motor system of the user and may impair performance and slow down learning. Although studies have shown that robotic outcomes are correlated with the case experience of the surgeon, the relative contribution of cognitive versus motor skill is unknown. This study quantified the effects of da Vinci Si master manipulator dynamics on movements of novice users and experienced surgeons and suggests possible implications for training and robot design.In the reported study, six experienced robotic surgeons and ten novice nonmedical users performed movements under two conditions: teleoperation of a da Vinci Si Surgical system and freehand. A linear mixed model was applied to nine kinematic metrics (including endpoint error, movement time, peak speed, initial jerk, and deviation from a straight line) to assess the effects of teleoperation and expertise. To assess learning effects, t tests between the first and last movements of each type were used.All the users moved slower during teleoperation than during freehand movements (F 1,9343 = 345; p < 0.001). The experienced surgeons had smaller errors than the novices (F 1,14 = 36.8; p < 0.001). The straightness of movements depended on their direction (F 7,9343 = 117; p < 0.001). Learning effects were observed in all conditions. Novice users first learned the task and then the dynamics of the manipulator.The findings showed differences between the novices and the experienced surgeons for extremely simple point-to-point movements. The study demonstrated that manipulator dynamics affect user movements, suggesting that these dynamics could be improved in future robot designs. The authors showed the partial adaptation of novice users to the dynamics. Future studies are needed to evaluate whether it will be beneficial to include early training sessions dedicated to learning the dynamics of the manipulator.

    View details for DOI 10.1007/s00464-014-3446-5

    View details for PubMedID 24519031

  • Wormholes in Host Defense: How Helminths Manipulate Host Tissues to Survive and Reproduce PLOS Pathogens Boyett, D., Hsieh, M. H. 2014
  • Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma Nature Cell Biology Shin, K., Lim, A., Odegaard, J. I., Honeycutt, J. D., Kawano, S., Hsieh, M. H., Beachy, P. A. 2014
  • Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection Infection and Immunity Hsieh, Y., Fu, C., Hsieh, M. H. 2014
  • Immune responses to Schistosoma haematobium infection Parasite Immunology Odegaard, J. I., Hsieh, M. H. 2014
  • A New Mouse Model for Female Genital Schistosomiasis PLOS Neglected Tropical Diseases Richardson, M., Fu, C., Pennington, L. F., Honeycutt, J. D., Odegaard, J. I., Hsieh, Y., Hammam, O., Conti, S. L., Hsieh, M. H. 2014
  • The effect of a robot-assisted surgical system on the kinematics of user movements. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference Nisky, I., Hsieh, M. H., Okamura, A. M. 2013; 2013: 6257-6260


    Teleoperated robot-assisted surgery (RAS) offers many advantages over traditional minimally invasive surgery. However, RAS has not yet realized its full potential, and it is not clear how to optimally train surgeons to use these systems. We hypothesize that the dynamics of the master manipulator impact the ability of users to make desired movements with the robot. We compared freehand and teleoperated movements of novices and experienced surgeons. To isolate the effects of dynamics from procedural knowledge, we chose simple movements rather than surgical tasks. We found statistically significant effects of teleoperation and user expertise in several aspects of motion, including target acquisition error, movement speed, and movement smoothness. Such quantitative assessment of human motor performance in RAS can impact the design of surgical robots, their control, and surgeon training methods, and eventually, improve patient outcomes.

    View details for DOI 10.1109/EMBC.2013.6610983

    View details for PubMedID 24111170

  • Editorial comment. Urology Hsieh, M. H. 2013; 81 (3): 538-?

    View details for DOI 10.1016/j.urology.2012.07.108

    View details for PubMedID 23295134

  • Kinematic analysis of motor performance in robot-assisted surgery: a preliminary study. Studies in health technology and informatics Nisky, I., Patil, S., Hsieh, M. H., Okamura, A. M. 2013; 184: 302-308


    The inherent dynamics of the master manipulator of a teleoperated robot-assisted surgery (RAS) system can affect the movements of a human operator, in comparison with free-space movements. To measure the effects of these dynamics on operators with differing levels of surgical expertise, a da Vinci Si system was instrumented with a custom surgeon grip fixture and magnetic pose trackers. We compared users' performance of canonical motor control movements during teleoperation with the manipulator and freehand cursor control, and found significant differences in several aspects of motion, including target acquisition error, movement speed, and acceleration. In addition, there was preliminary evidence for differences between experts and novices. These findings could impact robot design, control, and training methods for RAS.

    View details for PubMedID 23400175

  • A Case of Genitourinary Crohn's Disease UROLOGY Weinberg, A. E., Hazard, F. K., Hsieh, M. H. 2012; 80 (5): 1132-1134


    Scrotal swelling in young boys is a common problem. The differential diagnosis includes testicular torsion, epididymoorchitis, and idiopathic scrotal edema. We report the unusual case of a 17-year-old boy who presented with recurrent episodes of penile and scrotal edema as extraintestinal manifestations of Crohn's disease. Genitourinary complications of Crohn's disease are not uncommon; however, they more typically present in the form of nephrolithiasis, obstructive uropathy, and enterovesical fistulization. Few reports have described Crohn's disease presenting with isolated genital edema in the absence of associated intestinal or systemic symptoms.

    View details for DOI 10.1016/j.urology.2012.07.044

    View details for Web of Science ID 000310566300047

    View details for PubMedID 22999453

  • Editorial comment. journal of urology Hsieh, M. H. 2012; 188 (4): 1648-?

    View details for DOI 10.1016/j.juro.2012.02.2595

    View details for PubMedID 22910258

  • Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance HUMAN REPRODUCTION Hsieh, M. H., Eisenberg, M. L., Hittelman, A. B., Wilson, J. M., Tasian, G. E., Baskin, L. S. 2012; 27 (6): 1577-1580


    Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals.Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Children's Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Student's t-tests.One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant.In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.

    View details for DOI 10.1093/humrep/des087

    View details for Web of Science ID 000304530900004

    View details for PubMedID 22434852

  • Robot-Assisted Versus Open Sacrocolpopexy: A Cost-Minimization Analysis JOURNAL OF UROLOGY Elliott, C. S., Hsieh, M. H., Sokol, E. R., Comiter, C. V., Payne, C. K., Chen, B. 2012; 187 (2): 638-643


    Abdominal sacrocolpopexy is considered a standard of care operation for apical vaginal vault prolapse repair. Using outcomes at our center we evaluated whether the robotic approach to sacrocolpopexy is as cost-effective as the open approach.After obtaining institutional review board approval we performed cost-minimization analysis in a retrospective cohort of patients who underwent sacrocolpopexy at our institution between 2006 and 2010. Threshold values, that is model variable values at which the most cost effective approach crosses over to an alternative approach, were determined by testing model variables over realistic ranges using sensitivity analysis. Hospital billing data were also evaluated to confirm our findings.Operative time was similar for robotic and open surgery (226 vs 221 minutes) but postoperative length of stay differed significantly (1.0 vs 3.3 days, p <0.001). Base case analysis revealed an overall 10% cost savings for robot-assisted vs open sacrocolpopexy ($10,178 vs $11,307). Tornado analysis suggested that the number of institutional robotic cases done annually, length of stay and cost per hospitalization day in the postoperative period were the largest drivers of cost. Analysis of our hospital billing data showed a similar trend with robotic surgery costing 4.2% less than open surgery.A robot-assisted approach to sacrocolpopexy can be equally or less costly than an open approach. This depends on a sufficient institutional robotic case volume and a shorter postoperative stay for patients who undergo the robot-assisted procedure.

    View details for DOI 10.1016/j.juro.2011.09.160

    View details for Web of Science ID 000299070400102

    View details for PubMedID 22177180

  • Transcriptional Profiling of the Bladder in Urogenital Schistosomiasis Reveals Pathways of Inflammatory Fibrosis and Urothelial Compromise PLOS Neglected Tropical Diseases Ray D, Nelson TA, Fu CL, Patel S, Gong DN, Odegaard JI, Hsieh MH 2012; 6 (11): e1912
  • A novel mouse model of S. haematobium egg-induced immunopathology PLOS Pathogens Fu CL, Odegaard JI, Herbert DR, Hsieh MH 2012; 8 (3): e1002605
  • Ex-premature infant boys with hypospadias are similar in size to age-matched, ex-premature infant boys without hypospadias JOURNAL OF PEDIATRIC UROLOGY Hsieh, M. H., Alonzo, D. G., Gonzales, E. T., Jones, E. A., Cisek, L. J., Roth, D. R. 2011; 7 (5): 543-547


    Studies have postulated that hypospadias, prematurity, and low birth weight are linked by defects in androgen signaling. To determine whether premature, hypospadiac boys are small and remain so, we compared their size at birth and at hypospadias repair to premature boys who underwent post-neonatal circumcision.We identified premature boys admitted to Texas Children's Hospital who underwent either hypospadias repair or circumcision after 4 months of age. Age, weight, and height at birth and surgery were recorded.Fifty-four boys had hypospadias and 34 did not. For hypospadiac boys, the mean birth weight and age, height, and weight at surgery were lower than for boys without hypospadias. More importantly, length-for-age and weight-for-age percentiles were also lower for hypospadiac boys. When subset analysis was performed on boys younger than 2 years at surgery, however, there were no significant differences in height or weight between hypospadiac and non-hypospadiac boys.Our series suggests that premature, hypospadiac boys are born smaller than age-matched, non-hypospadiac controls. However, there were no age-corrected size differences between hypospadiac and non-hypospadiac boys at surgery. This implies that hypospadiac boys exhibit post-neonatal 'rebound' growth. Global growth deficits, if any, do not persist in hypospadiac boys.

    View details for DOI 10.1016/j.jpurol.2010.08.001

    View details for Web of Science ID 000295432900009

    View details for PubMedID 20833109

  • Impact of Anatomical and Socioeconomic Factors on Timing of Urological Consultation for Boys With Cryptorchidism JOURNAL OF UROLOGY Bayne, A. P., Alonzo, D. G., Hsieh, M. H., Roth, D. R. 2011; 186 (4): 1601-1605


    Cryptorchidism is a common finding in infants and young boys. Early repair lessens the extent of testicular injury. We hypothesized that anatomical and socioeconomic factors affect the timing of consultation and treatment for boys with cryptorchidism.Under an institutional review board approved protocol we reviewed the records at a single institution of children who underwent exploration for unilateral or bilateral cryptorchidism. Demographic and anatomical factors were recorded.The median age of 677 boys at consultation and surgery was 20.3 and 28.9 months, respectively. Median age at consultation for boys with nonpalpable and palpable testicles was 12.3 and 20.9 months, respectively (p = 0.03). Boys with a concomitant penile anomaly had a younger median age at consultation than boys without a penile anomaly (8.5 vs 20.3 months, p <0.01). Demographic factors did not vary with respect to time to consultation and surgery (p >0.05). Multivariate analysis showed that abdominal site and concomitant penile anomaly were associated with earlier time to consultation (p = 0.02 and <0.01, respectively).The timing of consultation for boys with undescended testicles does not vary in regard to race, language or insurance type at this tertiary care institution. Instead, anatomical factors influenced age at consultation for boys with cryptorchidism. This suggests that in some geographic regions access to care is not restricted for minorities or noncommercially insured children.

    View details for DOI 10.1016/j.juro.2011.03.102

    View details for Web of Science ID 000295043000010

    View details for PubMedID 21855921

  • Editorial comment. journal of urology Hsieh, M. H. 2011; 186 (3): 1034-?

    View details for DOI 10.1016/j.juro.2011.04.122

    View details for PubMedID 21784473

  • The Relationship between Anogenital Distance, Fatherhood, and Fertility in Adult Men PLOS ONE Eisenberg, M. L., Hsieh, M. H., Walters, R. C., Krasnow, R., Lipshultz, L. I. 2011; 6 (5)


    Anogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men.A cross sectional study of consecutive men being evaluated for infertility and men with proven fertility was recruited from an andrology clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count).A total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p?=?0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p?=?0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.

    View details for DOI 10.1371/journal.pone.0018973

    View details for Web of Science ID 000290483600004

    View details for PubMedID 21589916

  • Editorial comment. journal of urology Hsieh, M. H. 2011; 185 (5): 1898-1899

    View details for DOI 10.1016/j.juro.2010.12.115

    View details for PubMedID 21421228

  • Surgical antibiotic practices among pediatric urologists in the United States JOURNAL OF PEDIATRIC UROLOGY Hsieh, M. H., Wildenfels, P., Gonzales, E. T. 2011; 7 (2): 192-197


    We hypothesized that there are practice variations in the use of surgical antibiotics by pediatric urologists in the United States.A 31-question online survey was distributed to members of the Society of Pediatric Urology. The questionnaire examined physician preferences for surgical antibiotic use, including indications, antibiotic selection, timing of administration, and duration.189 pediatric urologists responded to the survey. >85% of responders give antibiotics before open pyeloplasty, after hypospadias repair (when a urethral catheter is left in place), or perioperative or postoperative antibiotics for open neoureterocystostomy or bladder reconstructive surgery. >90% of responders do not give postoperative antibiotics to children who have undergone circumcisions, simple chordee repairs, herniorrhapies, or hydrocelectomies. For all other open, laparoscopic, and endoscopic operations, use of antibiotics varied significantly. Diverse opinions exist regarding antibiotic use, including the importance of costs, potential adverse reactions, reduction in infection risk, and antibiotic resistance. There are major differences in gentamicin dosing and timing of administration of perioperative antibiotics.Perioperative and postoperative antibiotics are widely used by pediatric urologists. However, there is significant practice variation in surgical antibiotic administration with regards to most areas of pediatric urology, in particular laparoscopic, endoscopic and hypospadias surgery.

    View details for DOI 10.1016/j.jpurol.2010.05.001

    View details for Web of Science ID 000291195700019

    View details for PubMedID 20537590

  • Mouse bladder wall injection. Journal of visualized experiments : JoVE Fu, C., Apelo, C. A., Torres, B., Thai, K. H., Hsieh, M. H. 2011: e2523-?


    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

    View details for DOI 10.3791/2523

    View details for PubMedID 21775962

  • Factors Associated With Delayed Treatment of Acute Testicular Torsion-Do Demographics or Interhospital Transfer Matter? JOURNAL OF UROLOGY Bayne, A. P., Madden-Fuentes, R. J., Jones, E. A., Cisek, L. J., Gonzales, E. T., Reavis, K. M., Roth, D. R., Hsieh, M. H. 2010; 184 (4): 1743-1747


    Testicular torsion is a true urological emergency. We determined whether a delay in treatment due to hospital transfer or socioeconomic factors would impact the orchiectomy rate in children with this condition.We retrospectively evaluated the records of boys seen at a single institution emergency department who proceeded to surgery for a diagnosis of acute testicular torsion from 2003 to 2008. Charts were reviewed for transfer status, symptom duration, race, insurance presence or absence and distance from the hospital. Orchiectomy specimens were evaluated for histological confirmation of nonviability.We reviewed 97 records. The orchiectomy rate in patients who were vs were not transferred to the emergency department was 47.8% vs 68.9%, respectively (p = 0.07). Symptom duration was greater in the orchiectomy group with a mean difference of 47.9 hours (p <0.01). The mean transfer delay was 1 hour 15 minutes longer in the orchiectomy group (p = 0.01). Boys who underwent orchiectomy were 2.2 years younger than those who avoided orchiectomy (p = 0.01). Multivariate analysis showed that symptom duration and distance from the hospital were the strongest predictors of orchiectomy.Data suggest that torsion is a time dependent event and factors that delay time to treatment lead to poorer outcomes. These factors include distance from the hospital and the time delay associated with hospital transfer.

    View details for DOI 10.1016/j.juro.2010.03.073

    View details for Web of Science ID 000282618600055

    View details for PubMedID 20728168

  • Treatment of Pediatric Vesicoureteral Reflux Using Endoscopic Injection of Hyaluronic Acid/Dextranomer Gel: Intermediate-term Experience by a Single Surgeon UROLOGY Hsieh, M. H., Madden-Fuentes, R. J., Lindsay, N. E., Roth, D. R. 2010; 76 (1): 199-203


    Endoscopic injection of non-animal-stabilized hyaluronic acid/dextranomer gel is an increasingly recognized treatment option for vesicoureteral reflux. The procedure is minor compared with open surgery and, when successful, avoids the need for long-term antibiotic prophylaxis. We present data from 3 years of using non-animal-stabilized hyaluronic acid/dextranomer gel to treat children with vesicoureteral reflux.Pediatric patients aged 16 years with uncomplicated primary vesicoureteral reflux were recruited for endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel. A follow-up voiding cystourethrogram was scheduled at 2 weeks after treatment, and vesicoureteral reflux resolution was defined as grade 0. Repeat non-animal-stabilized hyaluronic acid/dextranomer gel treatment was offered to patients with persistent vesicoureteral reflux.Of 178 patients treated, 12 were lost to follow-up or yet to undergo post-treatment voiding cystourethrogram. The 166 remaining patients (efficacy population) had a mean age of 4.21 years (range: 0-16), and the median reflux grade was 3 (range: 1-5). Vesicoureteral reflux was resolved in 81.9% of patients and 86.4% of ureters after initial endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel. The overall reflux resolution rate for patients increased to 89.6% after a second treatment in 19 patients, and 90.2% after a third treatment in 1 patient. No adverse events were reported. Five patients underwent open ureteral reimplantation after failed endoscopic injections.Endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel is effective in a high proportion of children with vesicoureteral reflux and, in our opinion, should be considered as a first-line treatment option.

    View details for DOI 10.1016/j.urology.2009.10.034

    View details for Web of Science ID 000279442700065

    View details for PubMedID 20035980

  • The Genetic and Phenotypic Basis of Infertility in Men With Pediatric Urologic Disorders UROLOGY Hsieh, M. H., Hollander, A., Lamb, D. J., Turek, P. J. 2010; 76 (1): 25-31


    Male factor is a major component of infertility for many couples. The presence of congenital genitourinary anomalies in male partners can cause male infertility. We reviewed the state-of-the-art treatment and outcomes for male infertility caused by pediatric urologic disorders. Disorders were classified by whether they led to infertility through pre-testis, testicular, or post-testis effects. Despite the complexity of pediatric urologic disorders that can affect fertility, natural paternity and paternity through assisted reproductive technology are common. Given the significant recent advances in infertility treatments, paternity with many currently untreatable pediatric disorders is likely in the future.

    View details for DOI 10.1016/j.urology.2010.03.011

    View details for Web of Science ID 000279442700009

    View details for PubMedID 20451977

  • OEIS Complex Associated With Chromosome 1p36 Deletion: A Case Report and Review AMERICAN JOURNAL OF MEDICAL GENETICS PART A El-Hattab, A. W., Skorupski, J. C., Hsieh, M. H., Breman, A. M., Patel, A., Cheung, S. W., Craigen, W. J. 2010; 152A (2): 504-511


    OEIS complex (Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spine abnormalities) is a rare defect with estimated incidence of 1 in 200,000 live births. Most cases are sporadic, with no obvious cause. However, it has been rarely reported in patients with family members having similar malformations or with chromosomal anomalies. In addition, OEIS complex has been observed in association with environmental exposures, twinning, and in vitro fertilization. Monosomy 1p36 is the most common terminal deletion syndrome, with a prevalence of 1 in 5,000 newborns. It is characterized by specific facial features, developmental delay, and heart, skeletal, genitourinary, and neurological defects. We describe an infant with OEIS complex and 1p36 deletion who had features of both disorders, including omphalocele, cloacal exstrophy, imperforate anus, sacral multiple segmentation, renal malposition and malrotation, genital anomalies, diastasis of the symphysis pubis, microbrachycephaly, large anterior fontanel, cardiac septal defects, rib fusion, a limb deformity, developmental delay, and typical facial features. Chromosomal microarray analysis detected a 2.4 Mb terminal deletion of chromosome 1p. This is the first reported case with OEIS complex in association with a chromosome 1p36 deletion.

    View details for DOI 10.1002/ajmg.a.33226

    View details for Web of Science ID 000274508300041

    View details for PubMedID 20101692

  • Medicolegal Aspects of Minimally Invasive Urologic Surgery Complications of Robotic and Laparoscopic Urologic Surgery Meng MV, Hsieh MH 2010
  • Treatment of Pediatric Vesicoureteral Reflux Using Endoscopic Injection of Hyaluronic Acid/Dextranomer Gel: Intermediate-Term Experience by a Single Surgeon Urology Hsieh MH, Madden-Fuentes RJ, Lindsay EN, Roth DR 2010
  • Factors Associated with Treatment Delay in Patients with Acute Testicular Torsion: Do Demographics or Interhospital Transfer Matter? Journal of Urology Bayne A, Madden-Fuentes RJ, Cisek LJ, Gonzlaes ET Jr., Reavis KM, Roth DR, Hsieh MH 2010; in press
  • Transurethral Induction of Mouse Urinary Tract Infection Journal of Visualized Experiments Thai KH, Thathireddy A, Hsieh MH 2010; 42 (e2070): DOI: 10.3791/2070
  • Trends in prenatal sonography use and subsequent urologic diagnoses and abortions in the United States JOURNAL OF PEDIATRIC UROLOGY Hsieh, M. H., Lai, J., Saigal, C. S. 2009; 5 (6): 490-494


    Prenatal sonography has enabled fetal diagnosis of urologic conditions and is now commonly used in the US. The impact of this technology on the incidence of pediatric urological diagnoses is unknown. We sought to assess trends in prenatal sonography and resulting urologic diagnoses and/or abortions.Using administrative codes in Ingenix, a claims database of individuals with employer-based insurance, we identified women undergoing prenatal ultrasounds (1998-2005). These were linked to claims for subsequent abortions, live births, and postnatal urologic diagnoses in resulting offspring.99.07% of women underwent ultrasound and childbirth. Ultrasound use among women whose pregnancies proceeded to birth increased from 90,568 to 96,866 per 100,000 mother-infant pairs from 1998 to 2005. Of women who did or did not undergo ultrasounds, 1.25% and 0.66% had infants with urologic diagnoses, respectively. The rates of prenatal ultrasound-detected urinary tract anomalies increased from 1032.26 per 100,000 live births in 1999 to 1225.71 per 100,000 live births in 2005.Prenatal ultrasound is widely used, but increased utilization of this diagnostic modality did not seem to be associated with abortions. The rate of pediatric urologic diagnoses in infants who had received prenatal ultrasound did not rise significantly over time.

    View details for DOI 10.1016/j.jpurol.2009.07.002

    View details for Web of Science ID 000208054400013

    View details for PubMedID 19664960

  • Editorial comment. journal of urology Hsieh, M. H. 2009; 182 (4): 1687-?

    View details for DOI 10.1016/j.juro.2009.03.124

    View details for PubMedID 19692070

  • Meta-analysis: does lidocaine gel before flexible cystoscopy provide pain relief? BJU INTERNATIONAL Aaronson, D. S., Walsh, T. J., Smith, J. F., Davies, B. J., Hsieh, M. H., Konety, B. R. 2009; 104 (4): 506-509


    To consolidate previous reports and conduct a meta-analysis to draw further conclusions on the efficacy of the instillation of lidocaine gel before flexible cystoscopy, as it has had varying efficacy in several randomized controlled studies.We reviewed previous reports cited in PubMed, Biosis and the Cochrane Library, identified by a professional librarian searching for English language-only randomized controlled studies involving the keywords, lidocaine, cystoscopy, gel and pain, yielding 14 studies. Ten studies were excluded as they provided no comparison with appropriate control groups or contained insufficient data for analysis. Attempts to contact the authors of these studies yielded no additional data. A meta-analysis was conducted using a random-effects model.Four studies were included in the analysis, two double-blind and two single-blind, totalling 411 male patients. Three of the studies found no statistical improvement and one study found a statistically significant improvement in pain relief using lidocaine gel. Studies varied on the quantity of gel instilled and on the dwell time of gel before cystoscopy. The meta-analysis found that subjects who received anaesthetic-impregnated gel were 1.7 times more likely not to experience moderate to severe pain (<2, 3 or 30, based on the scale used; odds ratio 1.7, 95% confidence interval 1.1-2.8) than subjects who did not have intraurethral instillation of gel.These data suggest that intraurethral instillation of lidocaine gel vs plain lubricating gel reduces the likelihood of moderate to severe pain during flexible cystoscopy.

    View details for DOI 10.1111/j.1464-410X.2009.08417.x

    View details for Web of Science ID 000268217200013

    View details for PubMedID 19239453

  • Urologic Diagnoses Among Infants Hospitalized for Urinary Tract Infection UROLOGY Hsieh, M. H., Madden-Fuentes, R. J., Roth, D. R. 2009; 74 (1): 100-103


    To determine the prevalence of urologic disease among infants hospitalized for urinary tract infections (UTIs) at our institution. The prevalence of urologic anomalies among infants (<400 days old) hospitalized for UTIs has not been previously reported.We retrospectively examined the records of all infants hospitalized for UTI at our institution, a free-standing children's hospital in the United States, for a 10-year period. Race, sex, and subsequent urologic diagnosis (using codes from the 9(th) edition of the International Classification of Diseases [ICD-9] were tabulated. Individual charts were reviewed to confirm documentation and workup of UTI.We identified 914 infants hospitalized at our institution from January 1996 to December 2007, with an ICD-9-coded diagnosis of UTI. Of these 914 infants, 258 were subsequently given a urologic diagnosis. However, only 130 of these patients had well-documented UTI (14.2% of 914 children). Of this cohort, 55.4% were boys. The most common diagnoses were hydronephrosis (37.7%), vesicoureteral reflux (69.2%), and obstructive uropathy (23.1%).Our data have indicated that > or =14% of all infants hospitalized for UTI have urologic anomalies. Vesicoureteral reflux, obstructive uropathy, and hydronephrosis are common diagnoses. We therefore conclude that infants admitted with a diagnosis of UTI should undergo screening for anatomic abnormalities.

    View details for DOI 10.1016/j.urology.2009.02.012

    View details for Web of Science ID 000267802100023

    View details for PubMedID 19406456

  • Bladder Injuries During Laparoscopic Orchiopexy: Incidence and Lessons Learned JOURNAL OF UROLOGY Hsieh, M. H., Bayne, A., Cisek, L. J., Jones, E. A., Roth, D. R. 2009; 182 (1): 280-284


    Laparoscopic orchiopexy is a safe operation. However, the bladder can be injured during creation of the transperitoneal tunnel for the cryptorchid testis. We reviewed our experience with this complication.We searched the operative notes of patients who had undergone laparoscopic orchiopexy between August 15, 2002 and October 1, 2008, and identified bladder injuries and their treatment.A total of 93 patients underwent laparoscopic orchiopexies for 101 undescended testes during the study interval, with 3 procedures resulting in bladder injuries. The 3 operations varied with regard to whether the injury was recognized intraoperatively or postoperatively, and repaired in an open or laparoscopic fashion.Bladder injury during laparoscopic orchiopexy is a rare but serious complication that can be managed by an open or laparoscopic approach. We recommend placement of a urethral catheter and syringe assisted drainage of all urine from the bladder at the beginning of the operation, careful perivesical dissection particularly in children with prior inguinal surgery, filling and emptying of the bladder during the procedure, and maintaining a high index of suspicion especially when hematuria is observed.

    View details for DOI 10.1016/j.juro.2009.02.134

    View details for Web of Science ID 000266949800118

    View details for PubMedID 19450839

  • Economic Analysis of Infant vs Postpubertal Orchiopexy to Prevent Testicular Cancer UROLOGY Hsieh, M. H., Roth, D. R., Meng, M. V. 2009; 73 (4): 776-781


    To use decision analysis to determine the economic benefits of early vs late orchiopexy, specifically with respect to testicular cancer development and management. Studies have suggested that prepubertal orchiopexy might confer additional protection from the development of testicular cancer compared with postpubertal orchiopexy. Infant surgery is often performed by pediatric subspecialists and hence might be more costly. Although rare, testicular cancer can require significant medical expenditures.We examined the resource index (RI) (physician charges and hospital costs) from the medical establishment's perspective. Economic modeling was performed to determine whether early or late orchiopexy minimized the RI. The stage- and histologic-specific costs of subsequent testicular cancer were incorporated into our models. The variables were tested over realistic ranges in the sensitivity analysis to determine the threshold values.In the base case analysis, the RI for infant and postpubertal orchiopexy was $7500 and $10,928 per patient, respectively. The sensitivity analysis demonstrated that the costs for operating room time, physicians' fees, operative times, and baseline cancer risk were important parameters. However, only the surgeons' fees demonstrated threshold values. The RI for treating cancer and the cancer risk reduction after early orchiopexy did not significantly affect our models.Our models of orchiopexy for prevention of testicular cancer showed that infant orchiopexy is less costly than later surgery, provided that the surgeons' fees are not excessive. It appears that early surgery might significantly reduce the treatment costs of testicular cancer for cryptorchid boys and supports the current standard of care in the United States.

    View details for DOI 10.1016/j.urology.2008.10.059

    View details for Web of Science ID 000265110400027

    View details for PubMedID 19193413

  • 46,XX SRY-Negative True Hermaphrodite Siblings UROLOGY Dorsey, F. Y., Hsieh, M. H., Roth, D. R. 2009; 73 (3): 529-531


    The sex-determining region on the Y chromosome (SRY) gene guides male sexual development. However, individuals with sex reversal syndrome (46,XX males and 46,XX true hermaphrodites) lack the SRY gene and yet can still develop testes. We present 2 siblings with XX true hermaphroditism. Most cases of sex reversal syndrome are sporadic; however, reports have been published of familial occurrence, suggesting that 46,XX maleness and 46,XX true hermaphroditism are actually different manifestations of the same disorder of gonadal development, likely an autosomal dominant mutation with variable penetrance or an X-linked mutation.

    View details for DOI 10.1016/j.urology.2008.09.050

    View details for Web of Science ID 000264442000027

    View details for PubMedID 19038427

  • Obesity Does Not Decrease the Accuracy of Testicular Examination in Anesthetized Boys With Cryptorchidism JOURNAL OF UROLOGY Breyer, B. N., Disandro, M., Baskin, L. S., Hsieh, M. H. 2009; 181 (2): 830-834


    Given that the prevalence of childhood obesity is increasing in the United States, we tested the timely hypothesis that obesity hinders physical examination based localization of the cryptorchid testis.Body mass index and percentiles of weight for height and body mass index for age were calculated for boys undergoing surgery for cryptorchidism at the University of California San Francisco Children's Hospital and Children's Hospital of Oakland. Two definitions of obesity were examined, ie greater than 85% or greater than 95% for either percentile. Patients were examined in the office and under general anesthesia before the skin incision. Intraoperative testicular location was recorded for each patient. The numbers of correct and incorrect preoperative determinations of testicular location were stratified by weight classification. Results were analyzed using contingency tables and Fisher's exact test.A total of 161 boys were recruited, accounting for 171 testes. The predictive value of palpating a suspected testis preoperatively with patients under anesthesia was greater than 95% for all weight classifications (p <0.0001). The predictive value of not palpating a testis preoperatively under anesthesia was greater than 56% for obese boys and greater than 42% for nonobese boys (p <0.0001). The concordance rates between examinations in the office and those performed under anesthesia were 90.9% and 82.7% for obese and nonobese boys, respectively (p = 0.51). The predictive value of not palpating a suspected cryptorchid testis in the office was higher in nonobese boys than in obese boys (81% vs 22%, p <0.0001).In our series childhood obesity did not make preoperative testicular examinations under anesthesia less accurate. However, office examinations may be more accurate in nonobese boys.

    View details for DOI 10.1016/j.juro.2008.10.046

    View details for Web of Science ID 000262419900194

    View details for PubMedID 19095266

  • OEIS Complex Associated with Chromosome 1p36 Deletion: A Case Report and Review of the Literature American Journal of Medical Genetics: Part A El-Hattab AW, Skorupski JC, Hsieh MH, Breman AM, Patel A, Cheung SW, Craigen WJ 2009; In press
  • Invasive Neuroendocrine Tumor of the Kidney: a Case Report Rare Tumors Olweny EO, Hsieh MH, Buckley JC, McAninch JW 2009; 1 (2): 41-42
  • Increasing Incidence of Neuroblastoma and Higher Associated Mortality of Children From Nonmetropolitan Areas: Analysis of the Surveillance, Epidemiology and End Results Database J Pediatr Hematol Oncol Hsieh MH, Meng MV, Walsh TJ, Matthay KK, Baskin LS 2009; in press
  • The human microbiome and probiotics: implications for pediatrics. Current problems in pediatric and adolescent health care Hsieh, M. H., Versalovic, J. 2008; 38 (10): 309-327

    View details for DOI 10.1016/j.cppeds.2008.09.001

    View details for PubMedID 18992706

  • 3-dimensional neuroanatomy of the human fetal pelvis: Anatomical support for partial urogenital mobilization in the treatment of urogenital sinus JOURNAL OF UROLOGY Kalfa, N., Liu, B., Cao, M., Vilella, M., Hsieh, M., Baskin, L. S. 2008; 180 (4): 1709-1714


    Retrospective reviews suggest that the functional outcomes of surgery of the urogenital sinus have often been unsatisfactory and to our knowledge the long-term results of newer surgical techniques have yet to be evaluated. A precise understanding of pelvic fetal neuroanatomy is germane for optimizing surgical correction of the urogenital sinus.The pelves of 10 human female fetuses were serially sectioned. Masson's trichrome staining and immunochemistry for the neuronal marker S100 (Dako Corp., Carpinteria, California) along with anatomical computer reconstruction allowed 3-dimensional analysis of the nerves in relation to the pelvic structures as an animated motion picture.Two types of neuronal structures were identified. 1) A dense perivisceral foil of branching nerves closely surrounded the pelvic organs. The localization of most nerves was on the external faces of the viscera with a limited fraction in the rectovaginal and urethrovaginal septa. This innervation was from the anterior cephalad periurethral area to the posterior caudal perirectal area. 2) A significant amount of nerves surrounded the cephalad urethra on its anterior and posterior faces.Based on these anatomical data during surgical repair of a urogenital sinus we would advocate minimal mobilization of the lateral faces of the vagina, avoiding dissection of the proximal urethra above the pubic bone and electing a vaginal flap in severe cases.

    View details for DOI 10.1016/j.juro.2008.03.089

    View details for Web of Science ID 000259382400077

    View details for PubMedID 18708223

  • Outcomes and cost analysis of pyeloplasty for antenatally diagnosed ureteropelvic junction obstruction using Markov models UROLOGY Hsieh, M. H., Meng, M. V., Baskin, L. S. 2008; 72 (4): 794-799


    The optimal timing of pyeloplasty for children diagnosed with ureteropelvic junction obstruction (UPJO) after workup for antenatal hydronephrosis is disputed. We sought to examine the potential costs and clinical outcomes of treatment protocols featuring different indications for pediatric pyeloplasty using Markov models.Cost and outcomes analysis using Markov modeling was performed for three treatment algorithms: medical management, immediate pyeloplasty (during the first year of life), and pyeloplasty after no improvement on imaging. The costs were determined from the perspective of the medical institution. The variables tracked during Markov model simulation included age at resolution of UPJO, the proportion of patients with worsened hydronephrosis, the number of pyeloplasties, the number of pyelonephritis episodes, and costs. Sensitivity analyses were performed to determine which elements affected the model and to determine threshold values.Immediate pyeloplasty and pyeloplasty after no improvement on imaging resulted in rapid resolution of UPJO (mean age at resolution younger than 2 years) with lower rates of worsened hydronephrosis and pyelonephritis compared with observation alone. For the surgical protocols, the costs per resolved case of UPJO were greater than those for medical management alone at the probability values tested in the Markov models. The sensitivity analysis of all variables over realistic ranges demonstrated that the costs of surgery, annual antibiotics and imaging, and the rate of pyelonephritis were critical in determining the costs.Pediatric urologists should include practice-specific features such as the costs of surgery, annual antibiotics and imaging, and pyelonephritis rates when considering efficacious, yet less costly, treatment protocols for UPJO.

    View details for DOI 10.1016/j.urology.2007.12.093

    View details for Web of Science ID 000259845600021

    View details for PubMedID 18674802

  • Medical malpractice in American urology: 22-year national review of the impact of caps and implications for contemporary practice JOURNAL OF UROLOGY Hsieh, M. H., Tan, A. G., Meng, M. V. 2008; 179 (5): 1944-1949


    Of the economic pressures on physicians practicing in the United States medical malpractice and associated costs are a major component. State tort reform in the form of caps on noneconomic awards has been pursued to control insurance premiums and improve patient access to care. We comprehensively examined jury verdicts involving urologists and determined the nature of these cases and their relationship to changes in tort reform.We searched the LexisNexis database for all malpractice cases involving urologists using the search terms urologist and malpractice. The query included all cases between 1984 and 2005, which were categorized by state, year, amount and the nature of the injury.We identified 322 jury verdict cases, of which 175 (54%) were in favor of the defendant. In states with caps the median verdict settlement within or outside the periods of caps was $350,000 and $150,000, respectively. States without caps had a median verdict or settlement of $491,500. However, the number of suits and the size of the verdict/settlement in states with and without caps during this period did not appear to be related to tort reform. Common clinical situations, such as prostate cancer and transurethral prostate resection, accounted for most suits.Although the concept and goals of malpractice caps seem desirable, there is little evidence that decreased physician premiums and improved access to care have been achieved via tort reform. Thus, while state and national legislative efforts to limit the economic burden on urologists continue, the specialty of urology must look to other approaches to improve the situation.

    View details for DOI 10.1016/j.juro.2008.01.061

    View details for Web of Science ID 000255005300076

    View details for PubMedID 18355843

  • Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Current urology reports Hsieh, M. H., Breyer, B. N., Eisenberg, M. L., Baskin, L. S. 2008; 9 (2): 137-142


    Endocrine disruptors, such as environmental compounds with endocrine-altering properties, may cause hypospadias and cryptorchidism in several species, including humans. Anogenital distance is sexually dimorphic in many mammals, with males having longer anogenital distance on average than females. Animal models of proposed endocrine disruptors have associated prenatal exposure with hypospadias, cryptorchidism, and reduced anogenital distance. Human studies have correlated shorter anogenital distance to in utero exposure to putative endocrine disruptors. We review preliminary data suggesting that anogenital distance is reduced in boys with hypospadia and cryptorchidism. Hence, human hypospadias and cryptorchidism may be associated with reduced anogenital distance as a result of endocrine disruption.

    View details for PubMedID 18419998

  • Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation DIFFERENTIATION Shiroyanagi, Y., Liu, B., Cao, M., Agras, K., Li, J., Hsieh, M. H., Willingham, E. J., Baskin, L. S. 2007; 75 (10): 968-977


    During bladder development, primitive mesenchyme differentiates into smooth muscle (SM) under the influence of urothelium. The gene(s) responsible for this process have not been elucidated. We propose that the Sonic hedgehog (Shh) signaling pathway is critical in bladder SM formation. Herein, we examine the role of the Shh-signaling pathway during SM differentiation in the embryonic mouse bladder. Genes in the Shh pathway and SM expression in mouse embryonic (E) bladders (E12.5, 13.5, and 14.5) were examined by immunohistochemistry (IHC), in situ hybridization, and reverse transcription polymerase chain reaction (RT-PCR). To examine the effects of disrupting Shh signaling, bladder tissues were isolated at E12.5 and E14.5, that is, before and after bladder SM induction. The embryonic bladders were cultured on membranes floating on medium with and without 10 muM of cyclopamine, an Shh inhibitor. After 3 days, SM expression was examined by assessing the following: SM alpha-actin (SMAA), SM gamma-actin (SMGA), SM-myosin heavy chain (SM-MHC), Patched, GLI1, bone morphogenic protein 4 (BMP4), and proliferating cell nuclear antigen (PCNA) by IHC and RT-PCR. SM-related genes and proteins were not expressed in E12.5 mouse embryonic bladder before SM differentiation, but were expressed by E13.5 when SM differentiation was initiated. Shh was expressed in the urothelium in E12.5 bladders. Shh-related gene expression at E12.5 was significantly higher than at E14.5. In cyclopamine-exposed cultures of E12.5 tissue, SMAA, SMGA, GLI1, and BMP4 gene expression was significantly decreased compared with controls, but PCNA gene expression did not change. In cyclopamine-exposed E14.5 cultures, SMGA and SM-MHC gene expression did not change compared with controls. Using an in vitro embryonic bladder culture model, we were able to define the kinetics of SM- and Shh-related gene expression. Cyclopamine inhibited detrusor SM actin induction, but did not inhibit SM-MHC induction. SMAA and SMGA genes appear to be induced by Shh-signaling pathways, but the SM-MHC gene is not. Based on Shh expression by urothelium and the effects of Shh inhibition on bladder SM induction, we hypothesize that urothelial-derived Shh orchestrates induction of SM in the fetal mouse bladder.

    View details for DOI 10.1111/j.1432-0436.2007.00187.x

    View details for Web of Science ID 000251385500008

    View details for PubMedID 17490411

  • Decision analysis and Markov modeling in urology JOURNAL OF UROLOGY Hsieh, M. H., Meng, M. V. 2007; 178 (5): 1867-1874


    The process of decision making in medicine has become increasingly complex. This has developed as the result of increasing amounts of data, often without direct information or answers regarding a specific clinical problem. The use of mathematical models has grown and they are commonly used in all areas. We describe and discuss the application of decision analysis and Markov modeling in urology.We define decision analysis and Markov models, providing a background and primer to educate the urologist. In addition, we performed a complete MEDLINE database search for all decision analyses in all disciplines of urology, serving as a reference summarizing the current status of the literature.The review provides urologists with the ability to critically evaluate studies involving decision analysis and Markov models. We identified 107 publications using decision analysis or Markov modeling in urology. A total of 36 studies used Markov models, whereas the remainder used standard decision analytical models. All areas of urology, including oncology, pediatrics, andrology, endourology, reconstruction, transplantation and erectile dysfunction, were represented.Decision analysis and Markov modeling are widely used approaches in the urological literature. Understanding the fundamentals of these tools is critical to the practicing urologist.

    View details for DOI 10.1016/j.juro.2007.07.006

    View details for Web of Science ID 000250187000008

    View details for PubMedID 17868735

  • Markov modeling of vasectomy reversal and ART for infertility: how do obstructive interval and female partner age influence cost effectiveness? FERTILITY AND STERILITY Hsieh, M. H., Meng, M. V., Turek, P. J. 2007; 88 (4): 840-846


    To apply Markov models to assess the cost effectiveness of the relative impact of obstructive interval and female partner age on fertility using either assisted reproductive technology (ART) or vasectomy reversal, and elucidate the impact of these variables on fertility.Markov models based on review of published literature and available ART outcome data.University-based clinical practice.Simulation runs of 50,000 patients for each analysis.Varying vasectomy obstructive interval and maternal age.Cost effectiveness, willingness to pay (WTP), and net health benefit.Base case analysis showed ART yields a higher pregnancy rate and higher cost than vasectomy reversal. Sensitivity analysis showed female age has a greater effect on cost effectiveness than obstructive interval. At a WTP < $65,000, vasectomy reversal is more cost effective than ART. With increasing WTP, ART is more cost effective over wider windows of female age.Markov modeling of fertility after vasectomy suggests female age has more impact than vasectomy obstructive interval on cost effectiveness.

    View details for DOI 10.1016/j.fertnstert.2006.11.199

    View details for Web of Science ID 000250192800012

    View details for PubMedID 17544418

  • In utero exposure to benzophenone-2 causes hypospadias through an estrogen receptor dependent mechanism JOURNAL OF UROLOGY Hsieh, M. H., Grantham, E. C., Liu, B., Macapagal, R., Willingham, E., Baskin, L. S. 2007; 178 (4): 1637-1642


    Additives such as benzophenone-2 are commonly used in cosmetic products and food container plastics to filter out ultraviolet light. In pregnant women exposure may result in transplacental transfer of benzophenone-2 to fetuses. Benzophenone-2 is estrogenic in vitro and in the rat uterotropic assay. Estradiol causes hypospadias in mice and estrogen-like compounds are also postulated to cause hypospadias. We determined whether hypospadias would develop in male mice exposed to benzophenone-2 in utero and whether this outcome depended on estrogen receptor pathways.Timed pregnant C57BL/6 mice were administered benzophenone-2 (6.25 mg) or control vehicle by oral gavage from gestational days 12 through 17 and they were sacrificed on day 18. Fetuses were weighed and sexed, anogenital distance was measured and genital tubercles were harvested for paraffin sections or quantitative reverse transcriptase-polymerase chain reaction analysis of genes purportedly involved in genital tubercle development.Eight of 57 benzophenone-2 treated male fetuses (14%) whose genital tubercles were examined histologically had hypospadias (p = 0.0064). Co-administration of benzophenone-2 with the estrogen receptor antagonist EM-800 resulted in normal genital tubercles, ie no hypospadias, in 26 of 26 mice. Likewise no EM-800 or control treated male genital tubercles showed hypospadias. Benzophenone-2 treated male mice had no changes in body mass adjusted anogenital distance relative to controls. Reverse transcriptase-polymerase chain reaction revealed that genital tubercles of benzophenone-2 treated male mice expressed higher levels of estrogen receptor-beta relative to male controls (p = 0.04).These findings suggest that benzophenone-2 may cause hypospadias via signaling through the estrogen receptor. Further study of human benzophenone-2 exposure and its effects is needed to support this hypothesis.

    View details for DOI 10.1016/j.juro.2007.03.190

    View details for Web of Science ID 000249568400024

    View details for PubMedID 17707034

  • Cost-utility analysis of treatment algorithms for moderate grade vesicoureteral reflux using Markov models JOURNAL OF UROLOGY Hsieh, M. H., Swana, H. S., Baskin, L. S., Meng, M. V. 2007; 177 (2): 703-709


    The optimal treatment algorithm for vesicoureteral reflux remains controversial. Previous decision analyses have attempted to determine the best approach solely from the cost or cure perspective but have not combined the goals of minimizing treatment and disease burden. We incorporated these considerations into a contemporary, comprehensive analysis of treatment for vesicoureteral reflux.We examined costs from the perspective of the medical institution, and utility from the perspective of parents of children with grades II and III vesicoureteral reflux. Cost-utility analysis using Markov modeling was performed to ascertain which of 5 treatment algorithms best minimized morbidity and cost. A higher utility value was based on minimizing treatment and disease burden. Measures of treatment and disease burden included duration of suppressive antibiotics, number of invasive studies, pyelonephritis episodes, endoscopic treatments and open operations. All variables were varied spanning realistic ranges during sensitivity analyses to determine threshold values.The protocol of no antibiotics or followup imaging yielded the best cost-utility for vesicoureteral reflux grades II and III. Sensitivity analysis of variables spanning realistic ranges demonstrated that utility penalties for invasive imaging and outpatient pyelonephritis were particularly important in determining the highest utility protocols, with threshold values ranging from -0.5 to -0.8.In our models of treatment for vesicoureteral reflux a noninterventional approach constitutes the highest utility and least costly treatment for moderate grade reflux. Given the relative dearth of randomized trials, these analyses provide guidelines for current management of vesicoureteral reflux.

    View details for DOI 10.1016/j.juro.2006.10.002

    View details for Web of Science ID 000243453900060

    View details for PubMedID 17222660

  • The effects of detethering on the urodynamics profile in children with a tetheredcord JOURNAL OF NEUROSURGERY Hsieh, M. H., Perry, V., Gupta, N., Pearson, C., Nguyen, H. T. 2006; 105 (5): 391-395


    Tethering of the spinal cord is a pathological fixation of the cord in the vertebral column that can result in neurogenic bladder dysfunction and other neurological problems. It occurs in patients with closed spinal dysraphisms and those in whom postoperative scarring develops following spina bifida closure procedures. The authors of this study sought to determine the effects of detethering on the urodynamic profile of children with a tethered cord.The authors retrospectively reviewed the records of children who underwent surgical release of a tethered cord at a single institution between 2001 and 2003. They identified 17 children (nine girls and eight boys) who had undergone both preoperative and postoperative urodynamic evaluation. Preoperatively, 10 (59%) of the children with a tethered cord had abnormal urodynamic study (UDS) results. Only two (20%) of these patients had urological symptoms. All seven patients with normal preoperative UDS results had normal UDS results after detethering. In addition, in five (50%) of the 10 children with abnormal preoperative UDS results, the postoperative UDS demonstrated improved or normal urodynamics.Because more than half of the children who underwent detethering were found to have abnormal preoperative UDS results, preoperative urodynamic evaluation should be performed in all cases in which detethering is considered. With regard to voiding function, detethering is relatively safe for children with normal preoperative UDS results. In children with abnormal preoperative UDS results, detethering may lead to improvement or even normalization of voiding, especially if the procedure is performed prior to 1 year of age. Finally, children with anorectal anomalies and a tethered cord may represent a subset of patients who are particularly likely to experience urodynamic improvement after detethering.

    View details for Web of Science ID 000241800600012

    View details for PubMedID 17328264

  • JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells. Nephron. Experimental nephrology Nguyen, H. T., Hsieh, M. H., Gaborro, A., Tinloy, B., Phillips, C., Adam, R. M. 2006; 102 (2): e49-61


    In renal epithelial cells, mechanical forces produced from urinary obstruction serve as potential mediators of apoptosis by activating specific intracellular signaling pathways. In this study, we sought to further define the role of JNK and p38 SAPK-2 pathway and caspase activation in stretch-induced apoptosis.Immortalized cell lines derived from the various components of the nephron were subjected to cyclical stretch and their differential apoptotic response was assessed. Pharmacologic inhibitors and Western blot analysis were used to assess the involvement of the MAPK pathways. Caspases' activity was assessed with ELISA and by Western blot analysis.Stretch-induced apoptosis was dependent upon the cell phenotype and the degree of stretch. In NRK-52E cells, it was mediated through both JNK and p38 SAPK-2 pathways, and inhibition of either pathway reduced the degree of stretch-induced apoptosis. Stretched cells showed increased activity of caspase-3 and -9 but not -2 or -8. Stretch-induced apoptosis was modulated by inhibition of caspase-3 and to a lesser extent by caspase-9.These findings suggest that stretch induces apoptosis in renal epithelial cells through the specific activation of JNK/SAPK and p38 SAPK-2 pathways and is dependent on the activation of caspase-3 and -9.

    View details for PubMedID 16179830

  • JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and-9 in NRK-52E renal epithelial cells NEPHRON EXPERIMENTAL NEPHROLOGY Nguyen, H. T., Hsieh, M. H., Gaborro, A., Tinloy, B., Phillips, C., Adam, R. M. 2006; 102 (2): 49-61

    View details for DOI 10.1159/000088401

    View details for Web of Science ID 000233364600002

  • Failed percutaneous balloon dilation for renal access: Incidence and risk factors UROLOGY Joel, A. B., Rubenstein, J. N., Hsieh, M. H., Chi, T., Meng, M. V., Stoller, M. L. 2005; 66 (1): 29-32


    To present our experience using balloon dilation and discuss secondary techniques to establish a percutaneous tract when balloon dilation fails. Balloon dilation is a safe and effective method to achieve percutaneous renal access, but it is not uniformly successful. Also, the failure rate and risk factors have not been well documented.We retrospectively reviewed our last 99 consecutive percutaneous renal procedures using a balloon system as our initial dilation modality. In all cases, the urologist achieved needle access. We determined the balloon failure rate, relationship to prior renal surgery and other patient-related factors, and success rate using secondary techniques of tract dilation.The balloon did not adequately dilate a tract in 17 (17% failure rate) of 99 cases. The risk factors for failure included a history of prior ipsilateral renal surgery (25% failure rate versus 8% without surgery) and subcostal compared with supracostal puncture (18% versus 9% failure rate). The failure rate was not increased when stratified by laterality, stone composition, stone size and location, or history of ipsilateral renal infection. Amplatz dilators were used in 16 refractory cases and were successful in 15. Metal Alken dilators were successfully used in 2 patients.The balloon dilation system is commonly used as the primary modality to establish percutaneous renal access. Although safe and effective (83%), the success rate drops dramatically in patients with prior ipsilateral renal surgery. Knowledge and skill with alternative dilation systems, such as Amplatz or metal Alken dilators, are necessary to successfully gain entry into all renal collecting systems.

    View details for DOI 10.1016/j.urology.2005.02.018

    View details for Web of Science ID 000232157500007

    View details for PubMedID 15992884

  • Molecular mechanism of apoptosis induced by mechanical forces INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 245 Hsieh, M. H., Nguyen, H. T. 2005; 245: 45-90


    In all biological systems, a balance between cell proliferation/growth and death is required for normal development as well as for adaptation to a changing environment. To affect their fate, it is essential for cells to integrate signals from the environment. Recently, it has been recognized that physical forces such as stretch, strain, and tension play a critical role in regulating this process. Despite intensive investigation, the pathways by which mechanical signals are converted to biochemical responses is yet to be completely understood. In this review, we will examine our current understanding of how mechanical forces induce apoptosis in a variety of biological systems. Rather than being a degenerative event, physical forces act through specific receptor-like molecules such as integrins, focal adhesion proteins, and the cytoskeleton. These molecules in turn activate a limited number of protein kinase pathways (p38 MAPK and JNK/SAPK), which amplify the signal and activate enzymes (caspases) that promote apoptosis. Physical forces concurrently activate other signaling pathways such as PIK-3 and Erk 1/2 MAPK, which modulate the apoptotic response. The cell phenotype and the character of the physical stimuli determine which pathways are activated and, consequently, allow for variability in response to a specific stimulus in different cell types.

    View details for DOI 10.1016/S0074-7696(05)45003-2

    View details for Web of Science ID 000233561000003

    View details for PubMedID 16125545

  • Complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of LLME-treated, MHC-sensitized donor lymphocytes EXPERIMENTAL HEMATOLOGY Hayashi, S., Hsieh, M., Peranteau, W. H., Ashizuka, S., Flake, A. W. 2004; 32 (3): 290-299


    In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT.BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell-depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-leucine methyl ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD.Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival.This study represents "proof in principle" that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

    View details for DOI 10.1016/j.exphem.2003.12.008

    View details for Web of Science ID 000220965600008

    View details for PubMedID 15003315

  • High-level allogeneic chimerism achieved by prenatal tolerance induction and postnatal nonmyeloablative bone marrow transplantation BLOOD Peranteau, W. H., Hayashi, S., Hsieh, M., Shaaban, A. F., Flake, A. W. 2002; 100 (6): 2225-2234


    Clinical application of allogeneic bone marrow transplantation (BMT) has been limited by toxicity related to cytoreductive conditioning and immune response. In utero hematopoietic stem cell transplantation (IUHSCT) is a nonablative approach that achieves mixed chimerism and donor-specific tolerance but has been limited by minimal engraftment. We hypothesized that mixed chimerism achieved by IUHSCT could be enhanced after birth by nonmyeloablative total body irradiation (TBI) followed by same-donor BMT. To test this hypothesis, mixed chimerism was created by IUHSCT in a major histocompatibility complex-mismatched strain combination. After birth, chimeric animals received nonmyeloablative TBI followed by transplantation of donor congenic bone marrow cells. Our results show that: (1) low-level chimerism after IUHSCT can be enhanced to high-level chimerism by this strategy; (2) enhancement of chimerism is dependent on dose of TBI; (3) the mechanism of TBI enhancement is via a transient competitive advantage for nonirradiated hematopoietic stem cells; (4) engraftment observed in the tolerant, fully allogeneic IUHSC transplant recipient is equivalent to a congenic recipient; and (5) host-reactive donor lymphocytes are deleted with no evidence of graft-versus-host disease. This study supports the concept of prenatal tolerance induction to facilitate nonmyeloablative postnatal strategies for cellular therapy. If clinically applicable, such an approach could dramatically expand the application of IUHSCT.

    View details for DOI 10.1182/blood-2002-01-0166

    View details for Web of Science ID 000177884800040

    View details for PubMedID 12200389

  • Leucyl-leucine methyl ester-treated haploidentical donor lymphocyte infusions can mediate graft-versus-leukemia activity with minimal graft-versus-host disease risk BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Hsieh, M. H., Varadi, G., Flomenberg, N., Korngold, R. 2002; 8 (6): 303-315


    L-leucyl-L-leucine methyl ester (LLME) prevents GVHD in several animal models by depleting dipeptidyl peptidase I (DPPI)-expressing cytotoxic cellular subsets. However, clinical application has been hampered by difficulties in stem cell engraftment following treatment of donor bone marrow inocula with LLME at the concentrations necessary to purge DPPI-expressing T-cells. Noting that T-cells can mediate graft-versus-leukemia (GVL) responses via both perforin (usually co-expressed in cytotoxic granules with DPPI) and Fas ligand pathways in a murine model, we hypothesized that LLME might be useful for treatment of delayed DLIs for potential GVL activity with a decreased risk of GVHD induction. In regard to the clinical setting, the ex vivo use of LLME for this purpose would circumvent any toxicity issues for donor stem cells, because by that time patients would have already achieved successful engraftment. For our preclinical studies, we used the haploidentical C57BL/6 (B6) (H2b) --> ((B6 x DBA/2)F1 (H(2b/d)) murine model with lethally irradiated hosts that had received transplants of T-cell-depleted bone marrow cells and were challenged with the MMD2-8 myeloid leukemia line (H2d) of DBA/2 origin. A DLI of LLME-treated donor splenocytes, from B6 mice presensitized to recipient alloantigens, was administered in varying doses 14 days post-marrow transplantation, and the potential for both GVHD and GVL activity was assessed. All mice that received any dose of LLME-treated DLI survived indefinitely, without evidence of cachexia nor B-cell hypoplasia, in contrast to the severe and lethal GVHD induced by mock-treated DLI. Histological analysis largely correlated with the symptomatic findings and revealed no GVHD-like lesions in the spleens of LLME-treated DLI recipients, although some mice displayed various degrees of hepatic mononuclear infiltration. Most notably, mice given LLME-treated DLI also experienced DLI dose-dependent increases in survival against the challenge with the MMD2-8 leukemia. LLME-treated splenocytes remained immunocompetent, as these cells could proliferate in response to mitogens and to restimulation with ovalbumin when used as a recall antigen. In conclusion, LLME-treated DLI possesses immune potential and, in particular, GVL activity without inducing clinically evident GVHD.

    View details for Web of Science ID 000176658800003

    View details for PubMedID 12108916

  • Differential use of FasL- and perforin-mediated cytolytic mechanisms by T-cell subsets involved in graft-versus-myeloid leukemia responses BLOOD Hsieh, M. H., Korngold, R. 2000; 96 (3): 1047-1055


    In graft-versus-leukemia (GVL) responses, the cellular subsets and effector mechanisms responsible for cytotoxicity against leukemic cells in vivo remain poorly characterized. A murine model of syngeneic GVL that features CD4(+) and CD8(+) T-cell responses against the MMB3.19 myeloid leukemia cell line has been previously described. MMB3.19 expresses high levels of functional Fas and tumor necrosis factor (TNF) receptors that do not transduce proapoptotic signals. Through the use of perforin- and Fas ligand (FasL)-deficient mice, it was demonstrated that CD4(+) T cells mediate anti-MMB3.19 effects in vivo primarily through the use of FasL and secondarily through perforin mechanisms. Conversely, CD8(+) T cells induce GVL effects primarily through the use of perforin and minimally through FasL mechanisms. Although the in vivo observations of CD8(+) T cells were reflective of their in vitro cytotoxic T lymphocyte (CTL) activity, for CD4(+) T cells, in vitro responses were dominated by the perforin pathway. In addition, the diminished capacity of T cells from perforin- and FasL-deficient mice to lyse MMB3.19 target cells appeared directly related to their deficient cytotoxic functions rather than to defects in activation because these cells were fully capable of mounting proliferative responses to the tumor cells. These findings demonstrate that GVL responses of T-cell subsets can involve preferential use of different cytotoxic mechanisms. In particular, these findings identify a role for both FasL-employing CD4(+) CTLs and the more novel perforin-utilizing CD4(+) T-cell subset in responses against a myeloid leukemia.

    View details for Web of Science ID 000088394000037

    View details for PubMedID 10910921

  • T-cell subsets mediate graft-versus-myeloid leukemia responses via different cytotoxic mechanisms BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Hsieh, M. H., Patterson, A. E., Korngold, R. 2000; 6 (3): 231-240


    Analysis of the cytotoxic effector mechanisms by which T-cell subsets mediate graft-versus-leukemia (GVL) activity is complicated by systems that use unfractionated T cells and leukemias that express alloantigens in addition to tumor-specific antigens. In this study, we used MMB1.10, a myeloid leukemia of C57Bl/6 (B6) origin, to examine the cytolytic pathways employed by syngeneic GVL-mediating, and therefore tumor antigen-specific, T-cell subsets. Wright-Giemsa staining and flow cytometric analysis indicated that MMB1.10 cells exhibited the morphology and markers most consistent with a monocytic-myeloid origin. Although reverse transcription-polymerase chain reaction analysis revealed that MMB1.10 cells expressed tumor necrosis factor (TNF) receptor types I and H, in vitro assays suggested that these cells were resistant to TNF-alpha-mediated cytotoxicity. For study of in vivo GVL responses, mice were challenged with MMBl.10 cells, lethally irradiated, and administered anti-Thy-1-treated (T-cell-depleted) bone marrow (ATBM) either alone or in combination with T-cell subsets from MMB1.10-presensitized mice. In regard to CD4+ donor T cells, 4 x 10(6) MMB1.10-presensitized wild-type (wt) cells exhibited increased GVL responses and survival values relative to tumor-challenged recipients of ATBM only. CD4 T cells from either perforin-deficient (pfp0) or Fas ligand (FasL)-deficient (gld) mice exhibited a lower level of GVL activity but did not produce any long-term survivors. Recipients of 5 x 10(6) wt B6 CD8+ T cells had significantly improved survival relative to tumor-challenged mice that received ATBM only. The same dose of gld CD8+ T cells exhibited a reduced but significant level of GVL activity, whereas cells from mice that were perforin-deficient or cytotoxicity doubly deficient (cdd) (ie, lacking perforin and FasL) exhibited no discernable GVL activity. Doubling the gld CD8+ T-cell dose to 10(7) cells resulted in further improved survival of recipients. We conclude that GVL effects mediated by CD4+ T cells can depend on either perforin- or FasL-mediated mechanisms, whereas the CD8+ T-cell subset is heavily dependent on perforin-mediated cytotoxicity.

    View details for Web of Science ID 000090022300003

    View details for PubMedID 10871148



    In all tissues that have been studied to date, dendritic leucocytes constitute only a small proportion of total cells and are difficult both to isolate and purify. This study reports on a method for the propagation of large numbers of dendritic cells (DC) from mouse spleen using granulocyte-macrophage colony-stimulating factor (GM-CSF) and their characteristics. Within a few days of liquid culture in GM-CSF, B10 BR (H-2k, I-E+) mouse splenocytes formed loosely adherent myeloid cell clusters. Mononuclear progeny released from these clusters at and beyond 4 days exhibited distinct dendritic morphology and strongly expressed leucocyte common antigen (CD45), CD11b, heat-stable antigen, Pgp-1 (CD44) and intercellular adhesion molecule-1 (ICAM-1; CD54). The intensity of expression of the DC-restricted markers NLDC 145 and 33D1, the macrophage marker F4/80, and Fc gamma RII (CDw32) was low to moderate, whereas the cells were negative for CD3, CD45RA and NK1.1. High and moderate levels, respectively, of cell surface staining for major histocompatibility complex (MHC) class II (I-Ek) and the B7 antigens (counter-receptors of CTLA4, a structural homologue of CD28) were associated with potent stimulation of unprimed, allogeneic T cells (B10; H-2b, I-E-). DC propagated in a similar fashion from DBA/2 mouse spleen proved to be strong antigen-presenting cells (APC) for MHC-restricted, syngeneic T-helper type 2 (Th2) cell clones specifically responsive to sperm whale myoglobin. Footpad or intravenous injection of GM-CSF-stimulated B10.BR spleen-derived DC into B10 (H-2b, I-E-) recipients resulted in homing of the allogeneic cells to T-cell-dependent areas of lymph nodes and spleen, where they strongly expressed donor MHC class II antigen 1-2 days later. These findings indicate that cells can be propagated from fresh splenocyte suspensions that exhibit distinctive features of DC, namely morphology, motility, cell-surface phenotype, potent allogeneic and syngeneic APC function and in vivo homing ability. Propagation of DC in this manner from progenitors present in lymphoid tissue provides an alternative and relatively convenient source of high numbers of these otherwise difficult to isolate but functionally important APC.

    View details for Web of Science ID A1995PZ44600020

    View details for PubMedID 7890296


    View details for Web of Science ID A1994NY30800027

    View details for PubMedID 7961212



    The checkerboard dilution test is widely used for evaluation of in vitro synergy for multiple drugs, although problems in performance, standardization, and interpretation have been noted. A major problem inherent in this commonly used method is the use of twofold dilutions for the antibiotic concentrations. We evaluated an alternative method proposed by Horrevorts and colleagues that preserved the twofold dilution scheme. Giant checkerboards were constructed from a series of component checkerboards using rifampin and minocycline against Staphylococcus aureus. We found that this method improved the stability of the fractional inhibitory concentration (FIC) indices, but required substantially more labor and generated other problems. FIC interpretation and calculation remained compromised by the twofold dilution scheme. We have analyzed the theoretical basis of the checkerboard and its FIC calculation and conclude that the twofold dilution with its exponential increase in dilutions makes this method of synergy evaluation inherently unstable. The principle of examining growth at multiple dilutions of combined antibiotics is valid for assessment of synergy, but newer methods need to be devised.

    View details for Web of Science ID A1993LA04200010

    View details for PubMedID 8495592



    To elucidate the epidemiology of widespread ciprofloxacin resistance in our Veterans Affairs medical center using whole cell DNA analysis.In vitro study of ciprofloxacin resistant and susceptible Enterobacteriaceae isolated during the course of a clinical epidemiologic study of quinolone resistance.Veterans Affairs Medical Center with acute care and long-term care divisions.We examined 40 ciprofloxacin-resistant strains of Serratia marcescens, Proteus mirabilis, and Providencia stuartii using restriction endonuclease analysis of whole cell DNA and compared them with concomitantly isolated ciprofloxacin sensitive strains. We sought to determine whether resistant strains were identical to susceptible strains, indicating in vivo emergence of resistant strains from susceptible strains, and whether resistant strains were shared among patients. All 26 ciprofloxacin-resistant S marcescens isolates shared a single ecoRI restriction pattern. Multiple patterns were seen in the ciprofloxacin-susceptible S marcescens isolates; however, several isolates had a pattern matching that of the resistant isolates. Similar results were seen among the P mirabilis isolates. Three different ecoRI patterns were found among the ciprofloxacin-resistant P stuartii isolates; none matched those found among the susceptible isolates. The frequency of spontaneous emergence of ciprofloxacin resistance in susceptible S marcescens strains with restriction pattern matching that of the resistant strains was significantly higher than that of nonmatching strains.Ciprofloxacin-resistant strains of Enterobacteriaceae became widespread within a short period of time. Resistant strains of S marcescens and P mirabilis arose from endemic susceptible strains. The resistant strain of S marcescens appeared to arise from a susceptible strain with a relatively high frequency of spontaneous ciprofloxacin resistance.

    View details for Web of Science ID A1992KD22800009

    View details for PubMedID 1337751

Conference Proceedings

  • Robot-Guided Sheaths (RoGS) for Percutaneous Access to the Pediatric Kidney: Patient-Specific Design and Preliminary Results Morimoto, T. K., Hsieh, M. H., Okamura, A. 2013

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