Retinoid signaling directs secondary lineage selection in pancreatic organogenesis

BACKGROUND/PURPOSE: Retinoid signaling plays an important role in many differentiation pathways. Retinoid signaling has been implicated in the induction of differentiation by pancreatic ductal cancer cell lines and in patients with pancreatic cancer. The authors wished to better understand the role of retinoid signaling in pancreatic development. METHODS: Embryonic pancreas was harvested from mice at serial gestational ages and immunohistochemical analysis was performed for retinoic acid receptors (RAR-alpha, RAR-beta, RAR-gamma), and retinoid X receptors (RXR-alpha, RXR-beta, and RXR-gamma). Also, early embryonic pancreases were cultured for 7 days with exogenous 9-cis retinoic acid (9cRA) or all-trans retinoic acid (atRA) and analyzed histologically and immunohistochemically. RESULTS: Retinoid receptors were expressed in a lineage-specific distribution, with stronger expression for many in the exocrine compartment. The receptors were not often expressed until late gestation. Exogenous 9cRA induced predominantly ducts instead of acini, plus more mature endocrine (islet) architecture. Exogenous atRA induced predominantly acini instead of ducts, with no apparent endocrine effect. CONCLUSIONS: Retinoids may have an important role in pancreatic differentiation, with a particular effect on secondary lineage selection between ductal and acinar phenotype. Because the control of ductal versus acinar differentiation has been implicated strongly in the pathogenesis of pancreatic ductal carcinoma, these results may lay the groundwork for studies in the mechanism of induced differentiation of pancreatic ductal cancer by retinoids.     

Effects of immunosuppression on the rejection of methylcholanthrene tumor isografts

The effect of immunosuppression with azathioprine, methylprednisolone, or both, on primary and secondary immune responses to a transplanted tumor was studied. The ability to reject a methylcholanthrene-induced squamous cell carcinoma of the prostate in Lewis rats was determined by rechallenge with tumor cells after amputation of the primary transplant. Oral azathioprine (20 mg/ kg/day) increased the incidence of tumors in a primary challenge, but did not affect the ability of immunized rats to reject subsequent tumor isografts. Similar results were obtained with 2 mg/kg/ day intraperitoneal (IP) azathioprine, 2 mg/kg/day IP methylprednisolone, and the combination of 2 mg/kg/day IP methylprednisolone and 10 mg/kg/day IP azathioprine. It appears that immunosuppression by azathioprine affects the proliferation of sensitized cells during the immunological response to antigens of this specific tumor. Immunosuppression does not appear to alter substantially the processing of tumor-specific antigens or the cytotoxic effectiveness of the immune system. This data is reassuring to the concern of whether transplantation in patients previously cured of cancer is safe.     

Extracellular control of pancreatic differentiation

Our understanding of basic mechanisms of differentiation has evolved rapidly in the last two decades. Spurred by advances in molecular biology and other research technologies, these advances have become of heightened importance with the recent advent of the possibility of engineering different types of stem cells into needed cell and tissue sources. As pediatric surgeons, we have the potential to play a key role in interfacing between the basic science necessary to understand differentiation processes, and its application at the bedside. In this brief article, we outline our in-depth analysis of mechanisms of basic differentiation of pancreatic precursor cells in an effort to better understand ways in which we can engineer a stem cell pool to form mature pancreatic cells.     

An effective pyloromyotomy length in infants undergoing laparoscopic pyloromyotomy

BACKGROUND: Traditional management of pyloric stenosis has consisted of open pyloromyotomy during which the surgeon is able to palpate and determine whether the hypertrophied pylorus has been completely divided. During the last decade, laparoscopic pyloromyotomy has become an increasingly popular approach for this condition. The purpose of this study was to determine whether there is an effective pyloromyotomy length that will allow the surgeon to feel confident that a complete pyloromyotomy was performed with the laparoscopic approach. METHODS: All infants undergoing laparoscopic pyloromyotomy from October 1999 through October 2003 at a single institution were retrospectively studied. Clinical variables collected included the patient's age, gender, electrolyte status on admission, the elapsed time from admission to operation, ultrasonographic dimensions of the hypertrophied pylorus, operative time, the length of the pyloromyotomy performed, the time to initial and to full feedings, and the duration of the postoperative hospitalization. RESULTS: One hundred seventy-one patients comprised the study group. The age (mean +/- standard deviation) at the time of operation was 5.2 +/- 2.8 weeks. The mean preoperative ultrasonic measurements for both pyloric thickness and pyloric length were 4.3 +/- 0.7 mm and 19.5 +/- 2.8 mm, respectively. The average pyloromyotomy incision length for this entire group was 1.9 +/- 0.21 cm. The mean operative time was 23.5 +/- 8.3 minutes. There were no mucosal perforations, no conversions to an open procedure, and no evidence for an incomplete pyloromyotomy. CONCLUSIONS: Laparoscopic pyloromyotomy is a safe and effective technique for infants with pyloric stenosis. A pyloromyotomy incision length of approximately 2 cm appears to be an effective measure of a complete pyloromyotomy.     

Thyroglossal duct infections and surgical outcomes

Purpose

Thyroglossal duct cysts (TGDC) are the most common head and neck congenital anomalies in children and often present as infected neck masses. The authors reviewed their experience with TGDC to determine if preoperative infection was related to postoperative complications, including recurrence and postoperative infection.

Methods

The medical records of 99 patients undergoing excision of TGDC from January 1991 to July 2002 were reviewed. Factors thought to be associated with recurrence (age, history of infection, drainage, abscess, and operative procedure) were analyzed.

Results

Ninety-nine patients made up the study group. The mean age at operation was 5.0 years (range, 6 months to 16 years) with a male to female ratio of 1.6:1. TGDC recurred in 12.1% (12 of 99) of these patients. There was no gender difference for those with and without recurrence. The presence of an abscess or cellulitis preoperatively (22 of 99 patients) did not correlate with recurrence (NS). In addition, postoperative infection occurred in 13 of 99 patients and also was independent of preoperative infection. However, postoperative infection clearly was associated with an increased risk of TGDC recurrence. Seven of 87 patients without recurrence had a postoperative infection, whereas 6 of 12 of those who had a recurrence had a postoperative infection (P < .001). The mean follow-up was 3.7 years and was comparable for the 2 groups (recurrence v. resolution). Twelve patients successfully underwent a second procedure for recurrence.

Conclusions

In this large series of TGDC, preoperative infection occurred in approximately 1 of 5 patients and was not predictive of recurrence. Although postoperative infection did not correlate with the presence of preoperative infection, it was clearly associated with a statistically significant incidence of recurrent disease.     

Organogenesis Particularly Relevant to Fetal Surgery

In utero surgical intervention is an exciting frontier in medicine. Fetal surgeons strive to treat congenital anomalies definitively while organogenesis is still occurring. Many of these anomalies pose such a threat to the viability of the affected fetus that waiting until after the child is born to treat them is frequently not satisfying and too often unsuccessful. We review the embryology of selected systems that have associated aberrancies of development for which fetal surgery is particularly applicable. The surgeon can more effectively launch an assault against congenital anomalies when armed with a solid appreciation of normal development. Recognizing the critical period for the development of a system allows him or her to formulate the optimal time and mode of intervention.     

维生素K3粉末降解动力学

在温度为50～90℃,相对湿度为50～93%范围内,维生素K₃的变色速率方程为—dR/dt=k_RR,降解速率方程为d(C_o—c)/dt=k_C(c_o—c)^1/2,光解速率方程为—dR/dt=k_P(R_o—R)^-1。k_R和_C与热力学温度T和相对湿度RH的关系通式为k=k′exp(—E_A/RT)exp(m′RH)。在实验温度和湿度范围内,变色和降解的表观活化能平均值分别为105.51和130.72 kJ/mol。     

No-incision pubovaginal suspension for stress incontinence

We describe a modified needle suspension for urinary incontinence that eliminates all incisions. The anterior vaginal wall is suspended from the rectus fascia with 2 heavy nonabsorbable monofilament mattress sutures. The sutures pass down through and back up through the full thickness of the vaginal wall, and are tied suprapubically to bury the knot into the fat in the suprapubic puncture site. The technique is based on our laboratory observation that in rats and guinea pigs monofilament mattress sutures that are tied under tension to include the outside abdominal skin will cut through the skin, and become internalized and accepted without any residual inflammation if the knot is buried initially. The simplified technique makes routine use of outpatient surgery and allows for the use of local anesthesia only in selected patients. At 2 1/2 years the continence rate in the first 38 patients exceeded 87 per cent. There were no failures among the last 14 patients after the technique was modified to include an extra full thickness pass of the mattress suture through the vaginal wall. There have been no significant complications.