Aversion-induced drug taking and escape behavior involve similar nucleus accumbens core dopamine signaling signatures.

Dopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine self-administration sessions in which an acutely aversive 90 dB white noise was intermittently presented. In a separate group of rats, aversion-induced changes in dopamine were measured in an escape design in which operant responses terminated aversive white noise. Aversive white noise significantly reduced NAcC dopamine and increased cocaine self-administration in both male and female rats. The same relationship was observed in the escape design, in which white noise reduced dopamine and promoted escape attempts. In both designs, the magnitude of the dopamine reduction predicted behavioral performance. While prior research demonstrated that pharmacologically reduced dopamine signaling can promote intake, this report demonstrates that this physiological mechanism is naturally engaged by aversive environmental stimuli and generalizable to non-drug contexts. These findings illustrate a common physiological signature in response to aversion that may promote both adaptive and maladaptive behavior.

Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line.

In human tumor cells, experimental and clinical evidence indicates that some factors involved in signal transduction and cell growth can also modulate the response to chemotherapeutic treatment. The aim of the present study was to investigate the role of folic acid (FA) as a modulator of carboplatin (CBDCA) activity. Genotoxicity and cytotoxicity induced by CBDCA alone and in combination with FA were assessed in cultured HeLa cells. We used comet assay, mitotic index analysis, MTT and NR assays, cytokinesis-block micronucleus cytome assay and annexin V-IP as different cytotoxicity and genotoxicity approaches for human cervical carcinoma cell line studies. The results showed that addition of 900nM FA together with 40.4mM CBDCA enhanced the activity of the platinum compound, increasing its effect on cell death by nearly 20%, as evidenced by the MTT and NR assays. Moreover, not only higher levels of DNA and chromosomal damage were reached but also the number of necrotic and apoptotic cells were significantly increased when cell cultures were treated with the combined procedure. This situation opens the possibility to explore the use of FA in platinum-based chemotherapy protocols to reduce the platinum doses for patient treatment and decrease the chance of developing the known side effects without losing biological activity.

Mammography before post-operative radiotherapy in conservatively managed breast cancer patients: is it useful?

OBJECTIVE: The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast. METHODS: Patients with invasive breast cancer referred to the Radiotherapy Unit of the Università Cattolica del Sacro Cuore, in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation. RESULTS: 201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In two of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients. CONCLUSIONS: No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total dose of 50 Gy would have been inadequate. Given the low cost of mammography, further investigation about its role in pre-radiotherapy evaluation is warranted.

Adjunctive antipsychotic treatment of adolescents with bipolar psychosis.

BACKGROUND: A combination of an antipsychotic medication and a mood stabilizer is often used for initial treatment of acute psychotic mania. However, the optimal duration of this adjunctive antipsychotic medication is unknown. METHOD: As part of a lithium efficacy study, acutely manic adolescents with psychotic features were given open combination treatment with lithium and an adjunctive antipsychotic medication. If the psychosis resolved, the antipsychotic medication dose was gradually tapered and discontinued after 4 weeks of therapeutic lithium levels. The subject was then given a trial of maintenance lithium monotherapy for up to 4 weeks. RESULTS: Significant improvement was seen in 64% of the sample with psychotic features after 4 weeks of combination treatment. However, few maintained their response after discontinuation of the antipsychotic medication. Successful discontinuation of antipsychotic medication in this sample was associated with first episode, shorter duration of psychosis, and the presence of thought disorder at baseline. CONCLUSIONS: Adjunctive antipsychotic medication needs to be maintained for longer than 4 weeks in the vast majority of adolescents with psychotic mania, even though the manic and psychotic symptoms have resolved and lithium treatment is maintained. Future studies to determine the optimal duration of adjunctive antipsychotic medication treatment are warranted.

[Video-thoracoscopic sympathectomy in the treatment of Raynaud's disease and palmar hyperhidrosis]. / La simpaticectomia videotoracoscopica nel trattamento del morbo di Raynaud e dell'iperidrosi palmare.

BACKGROUND AND AIM: Raynaud's syndrome is a clinical entity characterised by episodic vascular spasm, digital ischemia in response to cold or emotional stimuli and hyperhidrosis. Many patients suffering from Raynaud's syndrome are successfully treated using medical therapy alone. Those patients who do not respond to medical treatment undergo surgery but the indications continue to be a source of controversy. A modern approach to thoracic sympathectomy requires a video-assisted technique. The aim of this study is to attempt to use mini-invasive type surgery to treat Raynaud's disease and hyperhidrosis in order to evaluate the real efficacy of thoracic sympathectomy in a large number of patients. The results of this method were compared for the two different pathologies in question. METHODS: The methodology used by this study is based on instrumental and clinical tests performed before and after surgery on treated patients using a comparative criterion and with a minimum 5-year follow-up. The pre- and postoperative diagnostic tests were performed by the vascular surgery laboratory and using a C.W. Doppler and a reflected light photoplethysmograph. Capillaroscopy and laboratory evaluations relating to secondary Raynaud's disease were carried out by internist type structures. The patients enrolled in the study responded to the following criteria: primary Raynaud's disease, palmar hyperhidrosis and associated syndromes. The population came from a mixed sociodemographic background, albeit within a strictly regional zone (Sardinia). A total of 42 patients were studied. The surgical technique used consisted of the ablation of thoracic ganglia from the 2nd to the 4th. RESULTS: The results showed a resolution of symptoms in 95% of patients treated for hyperhidrosis, whereas a 50% recidivation rate was observed in patients with Raynaud's disease alone, although symptoms were less intense. The results for Raynaud's disease were more disappointing, but it is important to remember that surgery is the ultimate choice for cases with advanced lesions which do not respond to medical treatment. Under these circumstances, the possibility of halting the evolution of the pathology represents an auspicious achievement. CONCLUSIONS: The authors affirm that mini-invasive surgical treatment of hyperhidrosis was resolutive during a mean follow-up of 3 years. It therefore represents a valid method which causes minimum esthetic damage to the patient and the greatest functional benefit. The postoperative period is short (about 3 days) and free of major complications. There is virtually no post-surgical pain.

[Videolaparoscopic treatment of biliary lithiasis. Evolution of our experience]. / Trattamento videolaparoscopico della litiasi biliare. Evoluzione della nostra esperienza.

Videolaparoscopic cholecystectomy is considered the treatment of choice for simple cholelithiasis. Now many surgeons consider the laparscopic procedure usable also in the complicated biliary lithiasis like acute cholecystitis and choledocholithiasis. The authors report their recent experience of the laparoscopic treatment of biliary lithiasis, regarding 221 non-selected patients (69% symptomatic cholelithiasis, 20% chronic cholecystitis, 4.5% acute cholecystitis, 4.5% coledocolithiasis, 2% hydrops). The diagnostic-therapeutic protocol and the results are described and compared with the beginning of their experience, when they treated only symptomatic gallbladder stone disease, and with the reports of the literature. The authors concluded that the laparoscopic procedure is a good chance for the surgeon in the treatment of all cases of benign biliary disease. But, in particular for patients with choledocholithiasis, he has be able to know all the diagnostic and therapeutic possibilities, to choose the best in every single case.

Are childhood psychiatric histories of bipolar adolescents associated with family history, psychosis, and response to lithium treatment?

OBJECTIVE: To examine if childhood psychiatric diagnoses are associated with family history, psychosis, age, and lithium response. METHOD: Associations among variables, and their contributions to explaining lithium response were examined in 48 bipolar adolescents enrolled in a study of lithium. RESULTS: Presence of a childhood diagnosis was not associated with family psychiatric history or lithium response. Subjects with psychotic features, however, were less likely to have a childhood psychiatric diagnosis, were older, and had a poorer response rate to lithium than subjects without psychosis. DISCUSSION: Heterogeneity within bipolar adolescents may be based on clinical features such as psychosis rather than childhood or family history alone.

[Minimally invasive surgery and neoplasms of the inferior third of the rectum: personal technique]. / Chirurgia miniinvasiva e neoplasie del terzo inferiore del retto: tecnica personale.

In the last decade minimally invasive surgery has gained an increasing success and was firstly applied to the treatment of benign pathologies, and recently to the malignant ones. The Authors report two cases of inferior rectal neoplasm treated with Miles operation through a video-laparoscopic-perineal approach. The abdominal phase of the operation was performed only through 5 small laparoscopic incisions. The perineal phase and the stoma were performed using traditional technique. The method appears feasible and oncologically correct; however, further trials are needed to evaluate long-term results.

[Laparoscopic cholecystectomy. Our experience]. / La colecistectomia laparoscopica. Nostra esperienza.

This study analysed 90 cases of symptomatic cholelithiasis treated with laparoscopic cholecystectomy. 27% of the cases studied suffered from microlithiasis, 44% from multiple calculosis with calculi measuring 1 to 2 cm in diameter, 25% from single calculi measuring up to 4 cm in diameter, and 4% from a benign proliferative pathology of the cholecystic wall. Calculosis of the main biliary tract was also found in 3 patients and was treated by preoperative endoscopic papillosphincterotomy. In addition to routine tests and ultrasonography, endovenous cholangiography, or retrograde cholangiography (ERCP) in cases of suspected calculosis of the biliary tract, was always performed prior to surgery. Mean operating time was 60 min. Two procedures were converted into laparotomy due to laceration of the cystic artery. In one case laparotomy was performed on day two due to choleperitoneum following a lesion of the cystic duct. Pneumoperitoneum could not be performed in three cases. Mean hospital stay was 48 hours. No other intra- or postoperative complications were reported. These results support the opinion that laparoscopic cholecystectomy is a safe method, with few limitations and represents the treatment of choice in the therapy of symptomatic cholelithiasis.

[Lipiodol chemoembolization in the treatment of hepatic carcinoma. Our experience]. / La chemioembolizzazione con Lipiodol nel trattamento del carcinoma epatico. Nostra esperienza.

Of the alternative methods of treatment to surgery in the treatment of liver cancer, chemoembolization with Lipiodol appears to have obtained encouraging results. After a preoperative study to confirm the diagnosis and staging of the tumour, lipiodolisation is performed: a mix of Adriamycin, Iopamidol and Lipiodol is injected using selective catheterism of the hepatic artery; gelfoam is then added. Lipiodol selectively localises in the hepatocarcinoma and has a distal embolising effect on the vessels of the tumour, thus necrotising it, acting as a carrier for chemotherapy. Since july 1990 a total of 15 hepatocarcinoma have been observed: 6 in healthy livers and 9 in cirrhotic livers; 3 patients recovered after radical surgery, 1 patient underwent associated surgery and chemoembolization, whereas in 11 the only therapy was chemoembolization, at six monthly intervals. Lipiodolisation enabled a better diagnosis to be made and was found to be a valuable therapeutic aid both when used alone in Inoperable patients and in association with non-radical surgery.

[Intraoperative pancreatic echography]. / L'ecografia pancreatica intraoperatoria.

The US intraoperative diagnostic procedure is useful either for the higher sensitivity rate or for the surgical decision making. The Authors' intraoperative diagnostic experience in pancreatic diseases is reported: 23 exocrine and endocrine neoplasms, 3 chronic pancreatitis and 8 acute pancreatitis cases are discussed.

[Carcinoid tumor in Meckel's diverticulum]. / Il carcinoide del diverticolo di Meckel.

The accidental finding of a carcinoid tumour in Meckel's diverticulum, a very uncommon event, triggered a physiopathological and clinical analysis of this very interesting but very rare association. The value of systematic identification and removal of the diverticulum during laparotomy is underlined.

[Circadian variations of bronchoconstriction in asthmatic children]. / Variazioni circadiane della broncoostruzione nel bambino asmatico.

In order to determine the magnitude of circadian variations in bronchoconstriction, we examined modifications of the spirometry observed during the 24-hr in a group of asthmatic (31 males, mean age = 8 years, 6 months). Particular attention was paid to the forced expiratory volume in 1 sec. (FEV1) and the forced vital capacity (FVC). We were thus able to compare in single patients 43 spirometry pairs between morning (between 8 and 10 am) and early afternoon (between 1 and 4 pm), 46 pairs between morning and evening (between 6 and 10 pm) and 54 between 2 consecutive mornings. The results of this study, substantially similar for the FEV1 and the FVC, show that the mean values obtained at different hours during the day and in two consecutive mornings were almost superimposable. On the other hand, the mean values and the standard deviations of the differences between two determinations in single patients are high. The percentage of patients who present significant modifications (greater than 10%) of FEV1 or of FVC at different hours of the day is also quite high. Moreover these variations seem directly related to the baseline spirometric value. Although the literature frequently outlines the existence of a circadian rhythm in the modifications or airways patency (maximum bronchoconstriction in the morning and minimum in the evening), in the asthmatic, however, the fast variations in the bronchial tone can be such as to mask this cyclic rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Impotence associated with pudendal arteriovenous malformation.

Three young men with impotence due to a pudendal arteriovenous malformation had a common selective pudendal arteriographic finding of early passage of contrast medium from the bulbar artery region into the venous drainage of the pelvis. Perineal exploration revealed the malformation and correction resulted in significant restoration of erectile capacity. This entity may be a frequent occurrence in young men that may become apparent only when trauma or disease affects the contralateral pudendal artery or its branches.

Treatment of asymptomatic metastatic cancer to the liver from primary colon and rectal cancer by the intraarterial administration of chemotherapy and radioactive isotopes.

Forty patients with asymptomatic metastatic cancer to the liver discovered at the time of laparotomy were treated by combined intrahepatic arterial chemotherapy and internal irradiation in the form of 90Yttrium microspheres. One group of 25 patients were treated by a catheter inserted at the time of operation and received 100 mCi; of 90Yttrium microspheres and 5-fluorouracil on a continuing basis. They survived an average of 26 mo (varying from 9 to 60 mo). The second series of 15 patients referred after surgery were treated by the percutaneous insertion of the catheter into the hepatic artery and received a bolus of combined chemotherapy consisting of PlatinolTM, Methotrexate, and 5-fluorouracil. They survived an average of 31 mo, which varied from 12 to 60 mo. The dose of 100 mCi of 90Yttrium was well tolerated by the liver. Prospective studies are in progress, limiting the treatment to the internal irradiation to determine its precise role in the overall treatment of metastatic cancer to the liver.