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The impact of mutations in different proteins, including RET, GDNF and GFRA1 on the development of renal aplasia in humans is discussed. The analysis reveals that the RET and GDNF mutations significantly contribute towards the development of abnormal kidney in patients.

Background We investigated the association between lack of insurance and mortality, resource use, and medical comorbidities among pediatric trauma patients. Methods Our trauma database was queried for patients < 18 years old from 1989 through 2013. Data collected included demographics, injury severity score (ISS), and insurance status. Dependent variables included major medical comorbidities, hospital and ICU lengths of stay (LOS), and mortality. Logistic regression and tests of equivalence were used to analyze the data. Results A total of 3120 patients were included. The mortality among patients with insurance was 3.6% compared to 8.4% among those without insurance ( p = 0.0001, OR = 2.42, 95% CI = 1.53–3.82). This relationship remained statistically significant with adjustment via multivariable logistic regression ( p = 0.0001, OR = 2.83, 95% CI: 1.64–4.74). Hospital and ICU LOS were significantly greater among insured patients in severely and moderately injured samples, respectively. There was no correlation between insurance and medical comorbidities. The uninsured mortality rate was 12.9% from 1989 to 1997 compared to 3.9% in 2006–2013. Conclusion Lack of insurance was associated with mortality but not preexisting comorbidity. This relationship persisted over time despite an overall decline in mortality. Additionally, lack of insurance was associated with decreased hospital stay and ICU utilization. Level of evidence Treatment Study, Level III. [ABSTRACT FROM AUTHOR]

Background/Purpose Thoracoscopic surgery has been increasingly utilized in treating pediatric congenital lung malformations (CLM). Comparative studies evaluating 30-day outcomes between thoracoscopic and open resection of CLM are lacking. Methods There were 258 patients identified in pediatric NSQIP with a CLM and pulmonary resection in 2012–2013. Comparisons of patient characteristics and outcomes between surgical approaches were made using standard univariate statistics. In addition, a propensity score match was performed to evaluate outcomes in similar patient cohorts. Results One-hundred twelve patients (43.4%) received thoracoscopic resections and 146 patients (56.6%) received open resections. Patients undergoing open resections were more likely to be less than 5 months of age and have a comorbidity/preoperative condition (47.3% vs. 25.0%, p < 0.001). The extent of resection was a lobectomy in 84.8% of thoracoscopic and 92.5% of open resection patients. Median operative time was similar between both groups (thoracoscopic 172 vs. open 153.5 minutes). On univariate analysis, thoracoscopic resection was associated with decreased postoperative complications (9.8% vs. 25.3%, p = 0.001) and LOS (3 vs. 4 days, p < 0.001). However, after adjusting for similar patient and operative characteristics, no significant differences were encountered between techniques. Conclusions Thoracoscopic and open resection provide comparable 30-day outcomes and safety in the management of congenital lung malformations. [ABSTRACT FROM AUTHOR]

Background The benefit of Ladd's procedure for malrotation at a Children's Hospital (CH) has not previously been established. Our aim was to characterize the potential variations in management and outcomes between CH and Non-Children's Hospitals (NCH) in the treatment of malrotation with Ladd's procedure. Methods There were 2827 children identified with malrotation and complete information from the Kids' Inpatient Database (2003, 2006, 2009). Outcomes were compared between CH and NCH and evaluated with logistic and linear regressions. Additional propensity score matching was used to balance covariates between CH and NCH. Results There were 2261 (80.0%) children with malrotation undergoing Ladd's procedures treated at CH; 566 (20.0%) were treated at NCH. In multivariate analysis, CH was associated with a 39% lower odds of resection ( p = 0.004), with no differences observed for mortality, morbidity and LOS. Comparison of a propensity score matched cohort confirmed these findings, as well as demonstrated no significant differences in associated costs. Conclusions The majority of pediatric intestinal malrotation is managed at CH. While measured outcomes of mortality, morbidity, LOS, and costs were not different at NCH, CH was less likely to perform intestinal resection during Ladd's procedure. [ABSTRACT FROM AUTHOR]

Pulmonary hyalinizing granuloma (PHG) is a rare benign pulmonary nodular lesion of unknown etiology. We present a case of a 5-year-old boy who was found to have a chest mass while being evaluated for abdominal pain. He underwent a CXR and CT scan that showed popcorn calcifications in the right posterior mediastinum and within the hilum of right lung. These lesions were suspicious for benign calcified lymph nodes and follow-up chest CT after 3.5 months showed no interval changes in the calcified mediastinal masses. Extensive testing ruled out infectious diseases and malignancies. Given the unknown etiology of the lesions, he underwent VATS biopsy that demonstrated a nodular lesion characterized by a peripheral rim of fibrous tissue and central zone of necrosis and calcification, findings consistent with hyalinizing granuloma. PHG is extremely rare in pediatric age group. Although diagnosis of this condition is made by radiological and histopathological findings, it is important to rule out other causes of chest masses. Most of the patients usually have good prognosis with this rare disorder. [ABSTRACT FROM AUTHOR]

Background. Off-road motorized vehicle crashes are a common source of trauma among Alaska children. Injury morbidity is worse in Alaska Native children than non-Native children, but the reasons are unclear. Objective. To evaluate the differences in helmet use between the Native and the non-Native children, and to assess the impact of helmet use on injury patterns and outcomes. Design. This retrospective cohort study identified patients aged 17 or younger admitted after all-terrain vehicle, snowmobile or motorbike injury between 2001 and 2011 from the Alaska Trauma Registry. Helmeted and non-helmeted patients were compared with respect to demographics, central nervous system (CNS) injury and the overall risk of death or permanent disability. Logistic regression was used to evaluate predictors of helmet use and the effects of ethnicity and helmet use on outcomes. Results. Of the 921 injured children, 51% were Alaska Native and 49% were non-Native. Helmet use was lower among Native versus non-Native patients on unadjusted comparison (24% vs. 71%) and multivariable logistic regression (OR 0.17, 95% CI 0.11-0.27, pB0.0001). Prevalence of CNS injury was higher among Native children (39.7% vs. 30.4%, p=0.016). However, on logistic regression with adjustment for helmet use, Native ethnicity was not a significant predictor of CNS injury (OR 1.07, 95% CI 0.68-1.68, p=0.78), whereas helmet use was strongly protective against CNS injury (OR 0.28, 95% CI 0.18-0.44, p<0.0001) as well as death or permanent disability (OR 0.26, 95% CI 0.10-0.67, p=0.006). Conclusions. Helmet use is lower among Alaska Native children involved in off-road motorized vehicle crashes. These ethnic disparities in helmet use contribute to higher rates of CNS injury among Native children. Helmet use significantly improves overall outcome. Helmet promotion efforts should be expanded, especially in Native communities. [ABSTRACT FROM AUTHOR]

Background. Paediatric trauma system development in Alaska is complicated by a vast geographic coverage area, wide regional variations in environment and culture, and a lack of available published data. Objective. To provide a detailed description of paediatric trauma mechanisms, high-risk injury patterns and outcomes in Alaska. Design. This retrospective study included all children aged 17 years or younger in the State of Alaska Trauma Registry database admitted with traumatic injury between 2001 and 2011. Each injury record was reviewed individually and assigned a mechanism based on Centers for Disease Control E-codes. Geographic definitions were based on existing Emergency Medical Services regions. Mechanisms were compared by geographic region, patient demographics, injury characteristics and outcome. Subgroup analysis of fatal injuries was performed to identify causes of death. Results. Of 5,547 patients meeting inclusion criteria, the most common mechanisms of injury were falls (39%), motor vehicle collisions (10%) and all-terrain vehicle (ATV) accidents (9%). The overall case fatality rate was 2%. Mechanisms with the greatest risk of death were gunshot wounds (21%), pedestrians struck by motorized vehicles (9%) and motor vehicle collisions (5%). These 3 mechanisms accounted for 15% of injuries but 60% of deaths in the overall cohort. Injury patterns involving combined central nervous system (CNS) and torso injuries were unusual but especially lethal, occurring in 3% of patients but carrying a case fatality rate of 18%. Although the distribution of mechanisms was generally similar for each geographic region, ATV and snowmobile injuries were significantly more common in remote areas (23% remote vs. 7% non-remote, p<0.0001). Conclusions. Mechanisms of paediatric trauma in Alaska have widely varying impacts on outcome and show some variation by region. Highest-risk mechanisms include gunshot wounds and motorized vehicle-related accidents. Prevention efforts should give special attention to CNS injury prevention, ATV and snowmobile safety in remote areas, and optimization of management of multisystem trauma. Further studies should investigate predictors of outcome in greater detail. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Surgical organizations have begun to focus their efforts on providing humanitarian assistance in international communities. Most surgeons do not have previous international experience and lack an understanding of what is expected and what care they can provide. The unknown factors include case types, patient volume, postoperative care, and equipment. This abstract presents humanitarian assistance mission and highlights the importance of preparation, host nation involvement, and understanding the local politics of each country. Methods: In April to July 2009, the USNS (United States Naval Ship) Comfort deployed to provide humanitarian assistance to 7 countries through Central and South America. Data collected included numbers and types of procedures, rate of rejection of patients for operation, patient age, American Society of Anesthesiology (ASA) score, and length of procedure. Results: These data represent the total mission of Continuing Promise 2009 including a total of 1137 surgical procedures of which 340 were pediatric (<18 years old). The average number of pediatric cases for each country in 7 days was 48.3 ± 21.4, with a range of 24 to 84. The average age was 7.5 years (range, 1 month to 18 years). In partnership with host physicians, preoperative screening occurred over 2 to 3 days for every 7 operative days. We maintained a low threshold for rejection (rate of 43%; range, 21%-62%) and average ASA score of 1.3. Including all pediatric subspecialties, the most frequent procedures were inguinal (23%) and umbilical (14%) hernias. Although these were the most frequent procedure, the range and variety of cases varied widely. We had a very low early complication rate (1.2%), including 3 wound infections and 1 early hernia recurrence. Conclusions: Our data represent the largest collection to date on the pediatric surgical care of children in a humanitarian effort. Our experience can be used to identify the most likely types of cases in South and Central America and as a model for the safe and efficient treatment of children in a developing country. [Copyright &y& Elsevier]

Abstract: Background: Intraoperative laparoscopic determination of intestinal viability is currently limited to subjective visible cues. Adjunctive modalities are neither widely available nor practical. Three–charge coupled device (3-CCD) imaging directly correlates the amount of light detected by CCDs to tissue oxygenation. We hypothesize that application of 3-CCD image enhancement detects bowel ischemia in a pediatric laparoscopic appendectomy model. Methods: We recorded 10 laparoscopic appendectomies for appendicitis. Offline analysis involved selecting regions of interest (ROIs) in the appendix, adjacent colon, and nonappendiceal fat and calculating mean intensity values in selected images before and after division of the mesoappendix. The colon was used as a control, and the intensity values were normalized to fat. Results: As an indicator of decreased perfusion, the mean appendix ROI intensity values decreased over time (R 2 = 0.92) compared with the colon mean ROI intensity values, which remained stable. There was a statistically significant difference between fat-normalized intensity values for ischemic and nonischemic appendix after 1 minute. Conclusion: We have demonstrated proof of principle for the determination of bowel ischemia using 3-CCD image enhancement. By quantitatively identifying areas of ischemia, this technique has the potential to significantly change the management of ischemic bowel in the future. [Copyright &y& Elsevier]

Abstract: Background: On January 12, 2010, Haiti experienced the western hemisphere''s worst-ever natural disaster. Within 24 hours, the United States Naval Ship Comfort received orders to respond, and a group of more than 500 physicians, nurses, and staff undertook the largest and most rapid triage and treatment since the inception of hospital ships. Methods: These data represent pediatric surgical patients treated aboard the United States Naval Ship Comfort between January 19 and February 27, 2010. Prospective databases managed by patient administration, radiology, blood bank, laboratory services, and surgical services were combined to create an overall patient care database that was retrospectively reviewed for this analysis. Results: Two hundred thirty-seven pediatric surgical patients were treated, representing 27% of the total patient population. These patients underwent a total of 213 operations composed of 243 unique procedures. Orthopedic procedures represented 71% of the total caseload. Patients returned to the operating room up to 11 times and required up to 28 days for completion of surgical management. Conclusions: This represents the largest cohort of pediatric surgical patients in an earthquake response. Our analysis provides a model for anticipating surgical caseload, injury patterns, and duration of surgical course in preparing for future disaster response missions. Moreover, we propose a 3-phased response to disaster medicine that has not been previously described. [Copyright &y& Elsevier]

Although diseases of the thyroid and parathyroid glands are relatively uncommon in children, the implications of missed diagnoses can be severe. This review describes the embryology, anatomy, and physiology of the thyroid and parathyroid glands, and focuses on significant benign and malignant pathologies of these glands. [Copyright &y& Elsevier]

Abstract: Aim: The availability of large clinical databases allows for careful evaluation of surgical practices, indicators of quality improvement, and cost. We used a large clinical database to compare the effect of surgeon and hospital volume for the care of children with hypertrophic pyloric stenosis (HPS). Methods: Patients with International Classification of Diseases-9 codes for HPS and pyloromyotomy were selected from the 1994 to 2000 National Inpatient Samples database. Multiple and logistic regression models were used to evaluate the risk-adjusted association between provider volume and outcomes. Results: Postoperative complications occurred in 2.71% of patients. Patients operated on by low- and intermediate-volume surgeons were more likely to have complications compared with those operated on by high-volume surgeons (95% confidence interval [CI], 1.25-3.78 and 95% CI, 1.25-2.69, respectively). Patients operated at low-volume hospitals were 1.6 times more likely to have complications compared with those operated at intermediate- or high-volume hospitals (95% CI, 1.19-2.20). Procedures performed at high-volume hospitals were less expensive than those at intermediate-volume hospitals by a margin of $910 (95% CI, $443-$1377). Conclusions: These data represent the largest study to date on the epidemiology, complication rate, and cost for care for HPS. Patients treated by both high-volume surgeons and at high-volume hospitals have improved outcomes at less cost. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study was to examine the association between E-cadherin expression and markers of Wilms'' tumor aggression, including metastasis and recurrence. Methods: Forty Wilms'' tumor samples from the National Wilms'' Tumor Study Group underwent immunohistochemical staining for E-cadherin. Tumor stage at diagnosis, recurrence, and loss of heterozygosity at 16q status was known for each of the tumor samples. E-Cadherin cell staining was defined as high (>33%) or low (<33%), and values were assigned by a pathologist blinded to the tumor characteristics. Five stage IV tumors were ineligible for assay because of lack of a tubular component. To identify a mechanism of downregulation, we screened tumor DNA for genetic mutations in exons 1-16 using a combination of WAVE and sequence analysis. To assess the functional significance of the identified mutations, the authors compared amino acid homology across multiple species. Finally, they performed reverse transcriptase–polymerase chain reaction for those tumors with intronic single nucleotide polymorphisms (SNPs) to evaluate for mRNA splice variants. Results: Wilms'' tumors presenting with metastatic (stage IV) disease demonstrated decreased levels of E-cadherin expression compared with localized tumors (stage I) (Fisher''s Exact test, P < .01). In a search for the mechanism of the downregulation of E-cadherin, we identified 5 different mutations in 7 high stage tumors (7/15) and 1 mutation in a low stage tumor (1/20). The mutations occurred in amino acids that were conserved across multiple species. Additionally, 11 of 15 high stage tumors contained an intronic SNP located within 6 bp of the 5′ intronic splice junction immediately downstream of exon 1. However, examination of 5 of these tumors using reverse transcriptase–polymerase chain reaction showed that this intronic SNP does not appear to disrupt the assembly of full-length E-cadherin transcripts. Lastly, no correlation was identified between E-cadherin expression and recurrence of disease. Conclusions: In this study, the authors have found an association between decreased E-cadherin expression and metastatic Wilms'' tumor. Mutations identified may help identify a mechanism for downregulation. The functional significance of these mutations is supported by the conserved nature of the amino acids across multiple species. The authors believe these findings support the involvement of E-cadherin in the evolution of Wilms'' tumor. [Copyright &y& Elsevier]

Investigates whether changes in auditory function accompany increases in the body size of gekkonoid lizards. Study of middle-ear structure of adult and juvenile Eublepharis macularius and Oedura marmorata; Compound action potentials (CAPs) which were used as an indication of peripheral auditory function; Study of tympanic membrane velocity; Results, which indicated that significant changes occurred between the younger and older animals.

Introduction: Nonoperative management of hemodynamically stable patients with blunt splenic and/or hepatic injury has been widely accepted in the pediatric population. However, variability exists in the utilization and timing of repeat imaging to assess for delayed complications during index hospitalization. Recent level-IV evidence suggests that repeat imaging in children should be performed based on a patient's clinical status rather than on a routine basis. The aim of this study is to examine the rate of delayed complications and interventions in pediatric trauma patients with blunt splenic and/or hepatic injuries who undergo repeat imaging prompted either by a clinical change (CC) or non-clinical change (NCC). Methods: A 9-year (2011-2019), retrospective, dual-institution study was performed of children (0-17 years) with blunt splenic and/or hepatic injuries. Patients were grouped based on reason for repeat imaging: CC or NCC. The rate of organ-specific delayed complications and interventions was examined by reason for scan. Results: A total of 307 injuries were included in the study period (174 splenic, 113 hepatic, and 20 both). Of 194 splenic injuries, 30(15.5%) underwent repeat imaging (CC = 19; NCC = 11). Of 133 hepatic injuries, 27(20.3%) underwent repeat imaging (CC = 21; NCC = 6). There was no difference in the incidence of organ-specific delayed complications between the CC and NCC groups. Of the 4 patients with complications necessitating intervention, only one was identified based on NCC. Conclusions: Our data suggest routine repeat imaging is unnecessary in children with blunt splenic and/or hepatic injuries; therefore, practitioners may rely on a patient's clinical change. [ABSTRACT FROM AUTHOR]

Surgical training includes the development of technical and nontechnical skills. While technical skills are more easily quantified, nontechnical skills such as situation awareness (SA) are more difficult to measure and quantify. This study investigated the relationships between different SA elements and expertise. Twenty attending and resident surgeons rated their anticipation of an impending adverse event while watching 20 videos of laparoscopic cholecystectomies with and without adverse events. After watching each video, they assessed surgeon skills and self-assessed their anticipation ratings. All participants answered a general confidence questionnaire before and after the study. Videos with adverse events led to significantly higher anticipation of adverse events (P < 0.001), lower surgeon skill rating (P < 0.001), and higher self-assessment in their anticipation ratings (P < 0.001) across both participant groups. General confidence was significantly lower for residents than that for attending surgeons (P < 0.001). Compared with the residents, attendings exhibited stronger and more stable correlations between measurements of SA. When viewing videos with adverse events, attendings showed significantly higher correlation between anticipation of an impending adverse event and skill assessment of the surgeon (P = 0.005). This study investigated how different elements of SA and their relationships were influenced by experience. The results indicated that attendings had stronger and more stable correlations between SA elements than residents, demonstrating how measurement correlations could be meaningful and sensitive indicators of expertise and autonomy readiness. [ABSTRACT FROM AUTHOR]

Background: The benefit of targeting high ratio fresh frozen plasma (FFP)/red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP/RBC transfusion and the association with outcomes in children presenting in shock., Methods: A post hoc analysis of a 24-institution prospective observational study (April 2018 to September 2019) of injured children younger than 18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (≥1:2) ratio FFP/RBC. Nonparametric Kruskal-Wallis and χ 2 were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths., Results: Of 135 children with median (interquartile range) age 10 (5-14) years and weight 40 (20-64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (low-38%, high-46%, p = 0.34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = 0.01); however, hospital mortality was similar (low-24%, high-20%, p = 0.65) as was the risk of extended ventilator, intensive care unit, and hospital days (all p > 0.05)., Conclusion: Despite increased injury severity, patients who received a high ratio of FFP/RBC had comparable rates of mortality. These data suggest high ratio FFP/RBC resuscitation is not associated with worst outcomes in children who present in shock. Massive transfusion protocol activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The function of the ear depends in part on its absolute size and internal proportions. Thus, in both young individuals and small species, the middle ear is expected to be allometrically enlarged despite its smaller absolute size. Here we aim to compare the ontogenetic allometry of relevant middle-ear structures as observed within gecko (gekkonomorph lizards) species, with the evolutionary allometry observed interspecifically. These observations also provide middle-ear data for future evaluation of variation in auditory sensitivity. The material comprised 84 museum specimens of geckos, representing nine species of three gekkonomorph subfamilies. The results of dissections and measurements show that different reports notwithstanding, the middle-ear ossicular chain is indeed structured as described for geckos by Werner and Wever. Some sexual dimorphism is indicated, but this requires further study. During postnatal ontogeny, the allometric growth in the ratio of the columellar footplate area to body length differed between the intraspecific and interspecific levels, hence species differences in the middle ear do not merely result from animal size. The ratio of the tympanic membrane area to the columellar footplate area increased during ontogeny. In this, geckos resemble birds and probably also mammals. Similarly, when the comparison was among adults representing different species, the ratio of the tympanic membrane area to the columellar footplate area increased with body size. In this, however, the geckos differed from birds and mammals, in which this ratio varied taxonomically, irrespective of body size. It would thus seem that middle-ear proportions have evolved among geckos to produce small interspecific differences, but among amniote tetrapods they have evolved according to different principles in the classes reptiles, birds, and mammals.

We generated a line of transgenic mice using a yeast artificial chromosome containing the Ret mutation responsible for the multiple endocrine neoplasia type 2B syndrome (MEN 2B). The resulting animals did not develop any of the expected neoplasms associated with MEN 2B. Transgenic animals were then bred with animals lacking murine Ret (Ret(M)) to further evaluate the function of human mutated Ret (Ret(H)(2B)) in the murine context. Whereas mice lacking Ret(M) exhibit intestinal aganglionosis and the absence of kidneys with other genitourinary anomalies, expression of the Ret(H)(2B) transgene in Ret(M)-deficient mice allowed significant renal development with a partial rescue of the enteric nervous system. These Ret(H)(2B)-positive/Ret(M)-deficient mice exhibit normal Ret expression and survive longer than Ret(M)-deficient mice, but still die at 3 to 5 days of age with evidence of enterocolitis. We conclude that the normal expression of a human Ret proto-oncogene with the MEN 2B mutation does not cause any features of MEN 2B in mice. Although the gene is normally expressed in the appropriate target tissues, there is incomplete phenotypic rescue in mice lacking murine Ret. These results suggest important interspecies differences between humans and mice in the function of the Ret oncogene.

Background: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors., Methods: The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response., Results: Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis., Conclusions: The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.

Background: Activating mutations in the RET receptor tyrosine kinase are responsible for the development of medullary thyroid cancer (MTC) in persons with Multiple Endocrine Neoplasia type 2. We hypothesized that STI571 (Gleevec) would inhibit RET kinase and be a useful agent in the treatment of MTC., Materials and Methods: We determined the IC50 of STI571 for RET using an in vitro kinase assay and also examined the effects of STI571 on cellular proliferation and viability in TT cells, a human MTC cell line., Results: The average in vitro IC50 of STI571 for RET is 37 microM +/- 4 microM. Additionally, TT cells incubated with 10 microM STI571 for up to 8 days showed no apparent reduction in cell proliferation or viability. Higher concentrations of STI571, from 25 to 100 microM, induced necrosis of TT cells., Conclusion: The concentrations of STI571 required to significantly inhibit RET and to inhibit TT cell proliferation are not clinically achievable. We conclude that STI571 is not likely to be an effective treatment for MTC.

The identification of cells capable of neuronal differentiation has great potential for cellular therapies. We examined whether murine and human adipose-derived adult stem (ADAS) cells can be induced to undergo neuronal differentiation. We isolated ADAS cells from the adipose tissue of adult BalbC mice or from human liposuction tissue and induced neuronal differentiation with valproic acid, butylated hydroxyanisole, insulin, and hydrocortisone. As early as 1-3 h after neuronal induction, the phenotype of ADAS cells changed towards neuronal morphology. Following neuronal induction, muADAS cells displayed immunocytochemical staining for GFAP, nestin and NeuN and huADAS cells displayed staining for intermediate filament M, nestin, and NeuN. Following neuronal induction of murine and human ADAS cells, Western blot analysis confirmed GFAP, nestin, and NeuN protein expression. Pretreatment with EGF and basic FGF augmented the neuronal differentiation of huADAS cells. The neuronal differentiation of stromal cells from adipose tissue has broad biological and clinical implications., ((c) 2002 Elsevier Science (USA).)