Guidelines for the management of postoperative soiling in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately achieve functional and comfortable stooling, some will experience a variety of problems after pull-through surgery. The most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative soiling in children with Hirschsprung disease. The American Pediatric Surgical Association Hirschsprung Disease Interest Group engaged in a literature review and group discussions. Expert consensus was then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with soiling symptoms following pull-through for Hirschsprung disease. Causes of soiling after pull-through are broadly categorized as abnormalities in sensation, abnormalities in sphincter control, and "pseudo-incontinence." A stepwise algorithm for the diagnosis and management of soiling after a pull-through for Hirschsprung disease is presented; it is our hope that this rational approach will facilitate treatment and optimize outcomes.

Effect of multiple binge alcohol on diet-induced liver injury in a mouse model of obesity.

BACKGROUND: Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are highly prevalent liver diseases that may coexist and contribute significantly to liver disease-related mortality. Obesity is a common underlying risk factor for both disorders. There has been little research investigating the combined effects of high fat diet (HFD) and alcohol. Current mouse models of alcohol- or fat-rich diet alone do not lead to severe liver injury. There is a need to develop animal models recapitulating human settings of drinking and diet to study the mechanisms of liver injury progression. METHODS: C57BL6 male mice were fed either chow or HFD ad libitum for 12 weeks. A sub-set of mice from each group were also given alcohol (2 g kg(-)(1) body weight) twice a week via intra-gastric lavage. Animals were monitored progressively for weight gain and blood and livers were harvested at termination. The extent of liver injury was examined by histopathology as well as by liver and serum biochemistry. The expression of lipid metabolism, inflammation and fibrogenesis-related molecules was examined by quantitative reverse transcription PCR (Q-PCR) and immunofluorescence staining. RESULTS: HFD significantly increased total body weight, triglyceride and cholesterol, whereas alcohol increased liver weight. Alcohol+HFD in combination produced maximum hepatic steatosis, increased micro- and macro-vesicular lipid droplets, increased de novo lipogenesis (steroid response-element binding protein 1 (SREBP-1) and stearoyl-CoA desaturase-1 (SCD-1)) and proliferation peroxisome activated receptor alpha (PPARα), and decreased fatty acid ß-oxidation (Acyl-CoA oxidase 1 (ACOX1)). Alcohol+HFD treatment also increased the inflammation (CD45+, CD68+, F4/80+ cells; tumour necrosis factor-alpha (TNF-α), F4/80 mRNAs) and fibrogenesis (vimentin+ activated stellate cells, collagen 1 (Col1) production, transforming growth factor-beta (TGF-ß) and Col-1 mRNAs) in mice livers. CONCLUSIONS: We report a novel mouse model with more severe liver injury than either alcohol or HFD alone recapitulating the human setting of intermittent alcohol drinking and HFD.

DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress.

The antineoplastic drug hydroxyurea (HU), when used at subtoxic doses, induces prolonged replication stress and centrosome amplification. This causes genomic instability and increases the malignancy of the recurring tumor. The mechanism of centrosome amplification induced by prolonged replication stress, however, is still unclear. Here, we examined the involvement of ataxia telangiectasia, mutated (ATM), ataxia telangiectasia, mutated and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) and found that HU-induced centrosome amplification was inhibited by the depletion of DNA-PKcs, but not ATM and ATR. Inactivation of ATM/ATR in U2OS cells instead caused aneuploidy and cell death. We found DNA-PKcs depletion also abrogated ATM phosphorylation, indicating that ATM activation during prolonged replication stress depends on DNA-PK. Depletion of DNA-PK abrogated checkpoint kinase (Chk)2 activation and partially reduced Chk1 activation. Chk2 depletion blocked HU-induced centrosome amplification, indicating a function of Chk2 in centrosome amplification. We further found that Chk2 was phosphorylated at Thr68 on the mother centriole at late G2 and mitosis when unstressed and on all amplified centrioles induced by HU. In summary, we have elucidated that DNA-PK/Chk2 signaling induces centrosome amplification upon long-term HU treatment, therefore increasing our insight into tumor recurrence after initial chemotherapy.

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose-volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer.

OBJECTIVE: We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose-volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose-volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). METHODS: The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle(3) system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2-T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V(20 Gy) and V(30 Gy) of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. RESULTS: Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V(20) (Gy), and heart V(30) (Gy) in the DV-gEUD plan were lower than those in the DV plan (p<0.05). CONCLUSIONS: A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV.

A novel radioresistant mechanism of galectin-1 mediated by H-Ras-dependent pathways in cervical cancer cells.

Galectin-1 is a lectin recognized by galactoside-containing glycoproteins, and is involved in cancer progression and metastasis. The role of galectin-1 in radiosensitivity has not previously been investigated. Therefore, this study tests whether galectin-1 is involved in the radiosensitivity mediated by the H-Ras signaling pathway using cervical carcinoma cell lines. A knockdown of galectin-1 expression in HeLa cells decreased clonogenic survival following irradiation. The clonogenic survival increased in both HeLa and C33A cells with galectin-1 overexpression. The overexpression or knockdown of galectin-1 did not alter radiosensitivity, whereas H-Ras was silenced in both cell lines. Whereas K-Ras was knocked down, galectin-1 restored the radiosensitivity in HeLa cells and C33A cells. The knockdown of galectin-1 increased the high-dose radiation-induced cell death of HeLa cells transfected by constitutively active H-Ras. The knockdown of galectin-1 inhibited the radiation-induced phosphorylation of Raf-1 and ERK in HeLa cells. Overexpression of galectin-1 enhanced the phosphorylation of Raf-1 and ERK in C33A cells following irradiation. Galectin-1 decreased the DNA damage detected using comet assay and γ-H2AX in both cells following irradiation. These findings suggest that galectin-1 mediates radioresistance through the H-Ras-dependent pathway involved in DNA damage repair.

Prenatal gastrointestinal development in the pig and responses after preterm birth.

Despite clinical research and medical advances, care of the preterm infant remains a clinical challenge, with the immature gastrointestinal (GI) system limiting the types and amounts of nutrients that can be provided enterally to meet energy and nutrient requirements. Progress in understanding the relationship between dietary inputs and the developing GI system after preterm birth has been limited by ethical constraints of using preterm infants as experimental subjects and a lack of relevant animal models. We review development of the GI system of the pig during gestation, the similarities shared with human fetuses, and the responses to dietary stimuli. The GI systems of pigs and humans develop early in gestation, with growth and maturation accelerating during the final weeks prior to birth. As a consequence, deficits in GI digestive capacities are directly related to how early in gestation an infant or pig is delivered, thereby complicating attempts to provide adequate enteral nutrients for growth and development. Pigs differ from humans by being born with low activities of the brush border membrane carbohydrases necessary for hydrolysis of nonlactose carbohydrates. Fetuses of both species have impaired lipid digestion coinciding with lipid malabsorption after preterm birth. Protease activity, although present, may not be adequate and may limit growth potential. Undigested enteral inputs are available to the resident bacteria and the production of metabolites can influence health and nutrition. The preterm pig represents a relevant and translational animal model for understanding GI development and for identifying diet and regulatory factors that stimulate GI growth and maturation after preterm birth and thereby accelerate the transition from parenteral nutrition to full enteral nutrition.

Establishment and characterization of a new marine fish cell line derived from red-spotted grouper Epinephelus akaara.

A new marine fish cell line, EAGL, derived from the liver of red-spotted grouper Epinephelus akaara was established and characterized. The cells multiplied well in minimum essential medium (MEM) supplemented with 10% foetal bovine serum (FBS) at temperatures between 25 and 30° C. The growth rate of this cell line increased as the proportion of FBS increased from 5 to 20% at 25° C, with maximum growth at the concentration of 15 or 20% FBS. Morphologically, the cells were epithelial-like and the presence of pancytokeratin confirmed their epithelial origin. Chromosome analysis revealed that the modal chromosome number was 48. The susceptibility of the cell line to four fish viruses was tested. Significant cytopathic effect (CPE) was only observed in Singapore grouper iridovirus (SGIV)-infected cells, and the virus replication was further confirmed by immunofluorescence, electron microscopy and real-time reverse-transcription (RT)-PCR assay. When the cells were transfected with pEGFP-N3 plasmid, bright fluorescent signals were observed, suggesting that this cell line can be used for transgenic and genetic manipulation studies.

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: the reduction of radiation-induced trismus.

The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last follow-up. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT.

Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series.

Non-iatrogenic subcutaneous metastasis of hepatocellular carcinoma (HCC) is rare. The aim of this study was to determine the characteristics of such non-iatrogenic subcutaneous metastases and to review the results of radiation therapy. Patients with HCC who were referred for radiation therapy to a subcutaneous mass from 1 January 1998 to 31 December 2005 were reviewed. Iatrogenic cases were excluded. The patients' characteristics, the properties of the lesion, radiation treatment, treatment response, and survival were studied. 24 subcutaneous metastatic lesions in 21 patients were studied. The patients' mean age was 58.2 years. The average latency period for the occurrence of the metastases was 291 days. The scalp was the most frequent metastatic site. At least a partial response was achieved in 20 of 24 lesions (83.3%), with radiation doses ranging from 8 to 64 Gy. No severe sequelae were recorded. The overall 6-month survival was 43.4%. ECOG (Eastern Cooperative Oncology Group) performance status and radiation dose were statistically significant factors for local treatment response. Performance status was also an independent factor for survival. Radiation therapy of subcutaneous metastases of HCC can achieve satisfactory results, especially in patients with a good performance status.

Interaction of maternal atopy, CTLA-4 gene polymorphism and gender on antenatal immunoglobulin E production.

BACKGROUND: Genetic heritability and maternal atopy have been correlated to antenatal IgE production, but very few studies have studied gene-maternal atopy interaction on antenatal IgE production. This study investigated the interaction of CTLA-4 polymorphism with prenatal factors on the elevation of cord blood IgE (CBIgE). METHODS: Pregnant women were antenatally recruited for collection of prenatal environmental factors by a questionnaire. Umbilical cord blood samples were collected for CBIgE detection by fluorescence-linked enzyme assay and CTLA-4 polymorphism measurement by restriction fragment length polymorphism. RESULTS: A total of 1104 pregnant women initially participated in this cohort study, and 898 of them completed cord blood collection. 21.4% of the newborns had elevation of CBIgE (>or=0.5 kU/L). The CTLA-4+49A allele (P=0.021), maternal atopy (P<0.001) and gender (P=0.034), but not the CTLA-4+49G allele, -318C allele, -318T allele, parental smoking or paternal atopy, were significantly correlated with the CBIgE elevation in multivariate analysis. A dichotomous analysis of gene-maternal atopy interactions identified maternal atopy and CTLA-4+49A allele had an additive effect on the CBIgE elevation, especially prominent in male newborns; and in the absence of maternal atopy, CTLA-4+49GG genotype had a protective effect on CBIgE elevation in female newborns. CONCLUSIONS: Maternal but not paternal atopy has significant impacts on CBIgE elevation depending on gender and CTLA-4+49A/G polymorphism of newborns. Control of maternal atopy and modulation of CTLA-4 expression in the prenatal stage may be a target for the early prevention of perinatal allergy sensitization.

Three-dimensional conformal radiotherapy for the treatment of arteriovenous shunting in patients with hepatocellular carcinoma.

The objective of this study is to evaluate the efficacy of radiotherapy for the treatment of arteriovenous shunting (AVS) in patients with hepatocellular carcinoma (HCC). Between November 1997 and April 2005, 20 HCC patients with AVS were referred to our department for radiotherapy. The radiation was delivered with 10-15 MV X-ray given 5 days per week at 2 approximately 2.5 Gy per fraction. Total doses ranged from 45 to 64 Gy (median dose 60 Gy). The patients were followed up with color Doppler sonography. When non-invasive imaging suggested obliteration, X-ray angiography was performed to verify the results. Four of the 20 AVS proved to be completely obliterated at X-ray angiography in 1.9, 2.8, 1.8 and 2.9 months after radiotherapy. One of the remaining 16 showed obvious regression on Doppler sonography 0.5 months after radiotherapy, but X-ray angiography was not performed to verify the result. Radiation-related hepatic failure did not occur during the follow-up period. In conclusion, radiotherapy is a treatment alternative for AVS in HCC patients and gives patients with poor prognosis the chance to receive further transcatheter arterial embolization.

Characteristics and predictive factors of early-onset diarrhoea during pelvic irradiation.

This study reported characteristics and predictive factors of early-onset diarrhoea in patients receiving pelvic irradiation. We retrospectively reviewed 229 patients undergoing radiotherapy alone for cervical or uterine cancer. Oral barium was taken 90 min before simulation. According to contrast medium within small intestine only or colon in simulation films, we categorised patients as normal and rapid transit groups. Small or large volume of small-bowel was also evaluated according to barium distribution of simulation films. Whole-pelvic irradiation (39.6-45 Gy/22-25 fractions) was delivered to all patients initially. We recorded the onset of diarrhoea during pelvic irradiation. The rates of early-onset diarrhoea (<10 Gy) were compared between these two groups. The incidence of diarrhoea before 10 Gy was 7% and 17% (p = 0.138) in patients with normal and rapid transit, respectively. In multivariate analysis, interaction among rapid transit, prior abdomen operation and large small-bowel volume (p = 0.019) were noted for early-onset diarrhoea. Further subgroup analysis revealed that rapid transit (p = 0.046) was a significant factor in patients with both prior abdominal operation and large small-bowel volume. The incidence of early-onset diarrhoea was as high as 40% in this particular group. Patients experiencing early-onset diarrhoea had a higher incidence of moderate to severe diarrhoea (65%) than those without early-onset diarrhoea (23%) (p<0.001). In multivariate analysis, early-onset diarrhoea was the only factor of moderate to severe diarrhoea (p = 0.001). In conclusion, rapid small-bowel transit may be predisposed to early-onset diarrhoea during pelvic radiotherapy in patients with both prior abdominal operations and large small-bowel volume. Early-onset diarrhoea is considered as a predictive factor of diarrhoea of a higher grade.

Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns.

The purpose of this study was to evaluate the treatment results and failure patterns of lymphoepithelioma-like carcinoma (LELC) of salivary glands. From June 1987 to May 2001, nine patients with LELC of salivary glands were treated at our hospital. One patient was excluded due to the loss of clinical follow-up after surgery. For the remaining eight patients, the primary tumour sites were parotid glands (4 patients), submandibular glands (3), and the minor salivary glands in right cheek (1), respectively. Seven patients underwent surgical treatment and post-operative radiotherapy, while the other one patient was treated with surgery only. The total radiation dose to the salivary tumour bed ranged from 39.6 Gy to 67.6 Gy (mean dose: 58.3 Gy and median dose: 59 Gy). The treatment results and failure patterns were analysed. The survival time ranged from 21.4 months to 145.2 months (mean: 69.1 months, median: 54.5 months). At the end of follow-up, six patients were still alive and two died. One patient died of distant metastases 21.5 months after the surgical treatment of LELC. The other case died of intercurrent disease (pontine haemorrhage) 53 months after surgery. No patient had local or regional failure after the treatments. Distant failure was noted in two patients. The patients with LELC of salivary glands were shown to have favourable prognoses. No local or regional failure was noted. However, distant failure developed in two patients. The risk of distant metastasis should be carefully monitored, especially for those patients with more advanced neck node involvement.

Treatment outcomes and prognostic factors in patients with supratentorial low-grade gliomas.

Low-grade gliomas account for 10-15% of all adult primary intracranial tumours. Currently, there is no consensus on the treatment strategy for low-grade gliomas. This study was designed to evaluate the treatment outcomes, prognostic factors and radiation-related late complications, as well as to assess whether or not post-operative radiotherapy has benefit on local control and overall survival in this population. We retrospectively reviewed 93 consecutive adult patients with supratentorial low-grade gliomas diagnosed at our institution from July 1985 to December 1997. All patients underwent surgical intervention and 60 of them received post-operative radiotherapy. With a median follow-up of 110 months for surviving patients, the 5-year overall and progression-free survival rates were 57% and 47%, respectively. 46 patients experienced local progression of disease during the follow-up period. In multivariate analysis, age at diagnosis, extent of surgery and post-operative Karnofsky performance status showed independent prognostic significance for progression-free and overall survival rates. Post-operative radiotherapy had independent prognostic value for progression-free survival. This analysis has changed our practice and we suggest that aggressive surgical resection and post-operative radiotherapy might be considered for patients with low-grade gliomas. Further efforts should be made to optimize radiotherapy techniques and to integrate new therapeutic modalities.

Early-onset sigmoid colon perforation during concurrent chemoradiation in a patient with cervical cancer.

Radiation-induced colon perforation is a rare adverse effect caused by vascular and connective tissue injury to the rectosigmoid colon. It usually occurs a few months to years after radiotherapy for gynecological cancer. Herein, we present a patient who developed sigmoid colon perforation during concurrent chemoradiotherapy for cervical cancer. The patient was a 64-year-old clinical stage IIB woman who received concurrent chemoradiotherapy as a standard treatment. The chemotherapeutic protocol was cisplatin 50 mg/m(2) and 5-fluorouracil 4000 mg, starting together with radiotherapy. After the completion of external beam radiation for 4500 cGy, the patient developed sigmoid colon perforation presenting with fecal peritoneum and sepsis. An emergency end ileostomy with resection of entire sigmoid colon was performed and the patient was discharged 3 months later in good condition. Clinicians must be highly suspicious of serious bowel perforation, even if the full dose of radiation has not been completed. Whether or not the chemotherapy was the trigger factor is in need of further clarification.

Post-operative adjuvant thoracic radiotherapy for patients with completely resected non-small cell lung cancer with nodal involvement: outcome and prognostic factors.

The purpose of this study was to analyse the outcome and prognostic factors of non-small cell lung cancer (NSCLC) patients with nodal disease treated by complete tumour resection followed by radiotherapy alone. Between October 1990 and October 1999, 49 NSCLC patients with N1 or N2 stage were treated with complete resection of tumour followed by post-operative radiotherapy in our department. The radiation was delivered with 10 MV X-rays given 5 days per week at 1.8-2 Gy per fraction. Total doses ranged from 40 Gy to 64.8 Gy, with a median dose of 55.8 Gy. All patients had at least 30 months of follow-up. The 5 year overall survival rate (OS), local control rate (LC) and distant metastasis-free rate (DMF) were 34%, 52% and 29%, respectively. In multivariate analysis, stage and margin were found to influence OS. The total number of involved lymph nodes and positive margins were significant factors for LC. Only N stage was found to correlate with DMF. In conclusion, patients with multiple involved lymph nodes, advanced stage or positive surgical margins had a poor outcome even with post-operative radiotherapy. Based on these prognostic factors, new therapeutic regimens and modalities for NSCLC need to be further investigated.

Wilms' tumor and horseshoe kidneys: a case report and review of the literature.

The presence of Wilms' tumor with a horseshoe kidney is an unusual combined clinical presentation. It has been reported that the incidence of Wilms' tumor in patients with horseshoe kidneys is higher than that seen in the general population. The current report describes a 5-year-old boy who presented with a stage III Wilms' tumor in a horseshoe kidney. The patient was treated with neoadjuvant chemotherapy followed by surgical resection, adjuvant chemotherapy, and radiation. The patient is disease free 40 months after diagnosis. A review of all reported cases of Wilms' tumor with horseshoe kidneys in the English-language literature before July 2002 is presented.

Endomorphin-1 and -2 induce naloxone-precipitated withdrawal syndromes in rats.

In 1997, endomorphin-1 (EM-1) and -2 (EM-2) were identified as the most specific endogenous mu-opioid ligands. These two peptides have shown analgesic effects and many other opioid functions. In the present study, we attempt to investigate the possible ability of endomorphins to induce naloxone-precipitated withdrawal in comparison with that induced by morphine. Using the previously established scoring system in rats, 12 withdrawal signs (chewing, sniffing, grooming, wet-dog shakes, stretching, yawning, rearing, jumping, teeth grinding, ptosis, diarrhea, and penile erection) were observed and scored following naloxone (4 mg/kg, i.p.) challenge. Compared with the sham control, EM-1 and EM-2 (20 microg, i.c.v., b.i.d. for 5 days) both produced significant naloxone-induced withdrawal syndromes with similar severity to that induced by the same dose of morphine. There was no significant difference between EM-1, EM-2, and morphine-treated group for naloxone-induced withdrawal signs, except for grooming. EM-1 and EM-2 induced more grooming than that caused by morphine. Although EM-1 and EM-2 both led to the withdrawal, they displayed different potency for certain signs and suggest their distinct regulations. The present results indicate EM-1 and EM-2 could initiate certain mechanism involved opiate dependence.

Predictive factors for skin telangiectasia following post-mastectomy electron beam irradiation.

This study evaluated the predictive factors associated with skin telangiectasia following post-mastectomy electron beam irradiation of the chest wall and regional lymph nodes in patients with breast cancer. From July 1987 to December 1994, 120 women with stages II and III breast cancer received electron beam irradiation following modified radical mastectomy. Doses of 50-50.4 Gy per 25-28 fractions were given to the chest wall (with bolus), the internal mammary nodes, the supraclavicular nodes and the axillary lymph nodes using a 12 MeV or 15 MeV single portal electron beam. 19 patients received an additional 10-16 Gy boost to the surgical scar using a 9 MeV electron beam. Univariate and multivariate analyses for the development of skin telangiectasia showed 5- and 7-year actuarial rates of telangiectasia to be 59% and 72%, respectively. In univariate analysis, an additional surgical scar boost (p=0.023) as well as no treatment interruption (p=0.028) were associated with a significantly increased risk of skin telangiectasia. In multivariate analysis, the only significant independent factor for the development of skin telangiectasia was surgical scar boost (p=0.026); no treatment interruption showed a trend but did not achieve significance (p=0.051). Thus, patients given an additional boost to the surgical scar are more likely to develop skin telangiectasia. Shorter treatment courses may result in a higher probability of skin telangiectasia following electron beam irradiation.

Dansyl-PQRamide, a possible neuropeptide FF receptor antagonist, induces conditioned place preference.

Neuropeptide FF (NPFF) is an endogenous anti-opioid peptide. NPFF could potentiate the naloxone-precipitated morphine withdrawal syndromes in morphine-dependent rats, indicating the possible involvement of the endogenous NPFF system in opioid analgesia and dependence. The present study was performed to examine the effects of dansyl-PQRamide (dns-PQRa), a putative NPFF antagonist, on conditioned place preference (CPP), in addition, its interaction with the opioid system. Two CPP experiments were conducted. First, rats were treated with dns-PQRa (4-13 mg/kg, i.p.) and paired with the non-preferred compartment while the vehicle was paired with the preferred compartment. Second, similar to experiment 1 except naloxone (1 mg/kg, i.p.) was given 10 min prior to each dns-PQRa administration. The post-drug place preference was examined after 4 alternative pairings. Another group of animals after repetitive dns-PQRa treatments were analyzed for levels of neurotransmitters in discrete brain areas. Dns-PQRa (4-13 mg/kg, i.p.) induced a significant dose-dependent CPP. The dns-PQRa-induced CPP was completely blocked by pretreatment with 1 mg/kg i.p. naloxone, while naloxone alone did not induce any place aversion. The chronic dns-PQRa-treated (13 mg/kg, i.p., b.i.d.) rats caused a significant increase in 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the olfactory tubercle compared to the vehicle-treated controls. There was also an increase in the turnover of serotonin in the olfactory tubercle, nucleus accumbens and medial prefrontal cortex. These results suggest that blockade of the NPFF system produces rewarding, possibly via an inhibition of the anti-opioid action of NPFF. These results also reveal a close relationship between NPFF, drug rewarding and the dopaminergic and serotoninergic neurons in the mesolimbic system.