Presently, there is no consensus on whether synchronous breast cancer has the same disease origin as the primary tumor, or if it is a completely independent second primary. This study explores this concept in both synchronous and metachronous breast cancer looking specifically at their receptor characteristics and level of differentiation. A retrospective chart analysis of 114 patients with synchronous or metachronous breast cancer treated at a single institution between January 1991 and March 2004 was done. Sixty-three per cent of the patients were diagnosed with metachronous breast cancer. Synchronous breast cancer was histologically more aggressive (P < 0.05) with a significantly higher number of patients having poorly differentiated tumors, a greater number of metastases involving a larger number of organs (P < 0.05), and lower average survival compared with the metachronous group (P < 0.005). Both the first and second tumor in both groups were similar in hormone receptor status, histologic subtype, and grade. Synchronous breast cancer is more aggressive and has a poorer outcome than metachronous breast cancer. Concordance in hormone receptor status, grade, and histologic subtype between different tumors within the same patient suggests, but does not completely support, a monoclonal origin. Analysis applied here is crude and more specific methods of analysis such as DNA microarray would be required to infer such a conclusion.

ABSTRACT Objective: The limited availability of donor sites for nerve grafts and the morbidity associated with their harvesting serve as motivating factors to actively conduct research to find alternatives to the status quo. Experimental and clinical studies have shown that a vein segment used to bridge a peripheral nerve defect leads to a functional nerve repair. Both FK-506 and b-FGF have been reported to enhance peripheral nerve regeneration. This study compared the effects of FK-506 with that of b-FGF on peripheral nerve regeneration in a rat autogenous vein graft conduit model. Methods: The main trunk of the right sciatic nerve was transected and bridged by an autogenous vein in 30 rats. Small osmotic pumps were placed just proximal to the anastomoses. Groups of 10 rats were assigned to receive saline solution, b-FGF (2,000 units), or FK-506 (0.5 mg/kg/day) via the osmotic pumps for 2 weeks. Sciatic nerve regeneration was evaluated by sensory function, walking track analysis, electrophysiologic studies, and light microscopic evaluation. Results: On post-operative day 90, there was a statistically significant difference (p <.005) in nerve regeneration between the rats who received saline compared with those who received FK-506 or b-FGF. This was determined using sensory function tests, sciatic function index, and electrophysiologic studies. The number of nerve axons, as determined by histological analysis, revealed there were significantly more nerve fibers which were regenerated in both experimental groups (FK-506 and b-FGF) when compared with rats who received saline. There was no statistically significant difference in the number of nerve axons that regenerated in rats injected with FK-506 vs. rats injected with b-FGF. Conclusion: FK-506 and b-FGF promote similar nerve regeneration in rats compared with control.

Thyroid cancer is three times more prevalent in females but the role of sex hormones in its pathogenesis is unknown. Vascular endothelial growth factor (VEGF) is crucial for angiogenesis. Its expression correlates with tumor aggressiveness and metastatic potential. We determined the expression of estrogen receptor (ER), progesterone receptor (PR), and VEGF-A in thyroid neoplasms to see if expression correlated with age and sex, histological type, cancer stage, and clinical outcome. Pathological samples of thyroid cancer diagnosed from 2002 to 2007 were stained immunohistochemically for ER, PR, and VEGF-A. Grading was done qualitatively in intensity and quantitatively in percentage. Both grades were multiplied to assign a final score. One hundred and four patients were studied, of which 82 per cent were female with a mean age of 53 years (range 23-86 years). Most tumors were papillary in origin. Overall, final scores were significantly higher for ER (1.41) and PR (1.0) in tumors compared with the ER (1.07) and PR (0.42) in normal tissue (P = 0.005 and < 0.001, respectively). Conversely, VEGF-A had lower expression in tumor tissues (7.2) than in normal tissue (8.2)(P = 0.024). No predilection was found for specific age group, gender, histological subtype, or stage of the cancer. Thus, compared with normal tissue, ER and PR expression is higher and VEGF-A expression is lower in tumor thyroid tissue. The overexpression of sex hormone receptors in thyroid tumor suggests their role in thyroid cancer pathogenesis and needs further investigation.

Psychosocial stress preceding the onset or recurrence of psychotic symptoms has been identified in patients with schizophrenia; yet there is limited understanding of the effects of stress in typically developing adolescents or those who show behavioral signs of risk for schizophrenia spectrum disorders. This study examined the developmental course of symptom progression as a function of stressful life events and daily hassles in adolescents with schizotypal personality disorder (SPD), other personality disorders, or no Axis II disorder. In this prospective longitudinal study, life events and daily stressors were assessed in adolescents aged 12 to 18 years. Results revealed that adolescents with SPD and other personality disorders reported significantly greater total, independent, and undesirable life events than individuals with no Axis II disorders. Youth with SPD report daily hassles to cause more distress compared to peers. Correlational analyses and hierarchal linear regression was used to evaluate the relationship of life events and daily stressors with psychiatric symptoms measured concurrently and 1 year later. Across diagnostic groups, the incidence of independent and undesirable life events were associated with current prodromal symptoms, while the frequency of daily stressors predicted a significant increment in positive, but not negative, prodromal symptoms over time. Therefore, adolescents who report greater daily stressors exhibit an increase in prodromal symptoms over a 1 year period. Psychosocial stress has been implicated in the etiology of schizophrenia, and these findings suggest the importance of life events and daily hassles as potential risk factors in the onset of psychotic symptoms during adolescence.

Diathesis-stress models of schizophrenia and other psychotic disorders have dominated theorizing about etiology for over three decades. More recently, with advances in our understanding of the biological processes mediating the effects of stress, these models have incorporated mechanisms to account for the adverse impact of stress on brain function. This review examines recent scientific findings on the role of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary neural systems triggered by stress exposure, in the expression of vulnerability for schizophrenia. The results indicate that psychotic disorders are associated with elevated baseline and challenge-induced HPA activity, that antipsychotic medications reduce HPA activation, and that agents that augment stress hormone (cortisol) release exacerbate psychotic symptoms. The cumulative findings are discussed in light of a neural diathesis-stress model that postulates that cortisol has the potential to increase activity of dopamine pathways that have been implicated in schizophrenia and other psychotic disorders.

ABSTRACT: BACKGROUND: Adenocarcinoma of the small bowel is a relatively rare malignancy as compared to the other malignancies of the gastrointestinal tract. Nonspecific presentation and infrequent occurrence often leads to a delay in diagnosis and consequent poor prognosis. Various other factors are of prognostic importance while managing these tumors. METHODS: The medical records of a total of 27 patients treated for adenocarcinoma of the small bowel at Providence Hospital and Medical Centers from year 1990 through 2003 were reviewed retrospectively. Data were analyzed using SPSS software (version 10.0; SPSS, Inc., Chicago, IL). Survival analyses were calculated using the Kaplan Meier method with the log rank test to assess the statistical significance. The socio-demographics (age, gender) were calculated using frequency analyses. RESULTS: The patients included nine males and eighteen females with a median age at diagnosis of 62 years. Only 48% of the patients had an accurate preoperative diagnosis while another 33% had a diagnosis suspicious of small bowel malignancy. None of the patients presented in stage 1. The cumulative five-year survival was 30% while the median survival was 3.3 years. There was no 30-day mortality in the postoperative period in our series. CONCLUSIONS: The univariate analysis demonstrated that tumor grade, stage at presentation, lymph nodal metastasis and resection margins were significant predictors of survival.

BACKGROUND: Roux Stasis Syndrome is a well-known complication after Roux-en-Y reconstruction. It has been hypothesized that reconstruction with an uncut Roux limb and jejunal pouch after total gastrectomy would preserve unidirectional intestinal myoelectrical activity, improve postoperative weight gain and nutritional parameters, and diminish Roux Stasis Syndrome in canines. METHODS: A total gastrectomy was performed, and 2 methods were used for reconstruction: Roux-en-Y esophagojejunostomy (RY) was performed on 5 canines (control), and the uncut Roux-en-Y with a jejunal pouch (URYJP) was performed on 5 other canines (experimental). The canines were monitored for 10 weeks postoperatively. Serial weight and nutritional parameters were measured. Emptying profiles and motility studies were performed in the fasting and postprandial states. RESULTS: Ten weeks after operation, the URYJP group had significantly improved nutritional parameters, including weight, total protein, albumin, hemoglobin, serum total iron binding capacity, and serum IgA, IgG, and IgM. The emptying times for both groups were similar, with an increase of disordered propagation of the jejunal pacesetter potential in the RY group. The aboral propagation occurred more frequently in the URYJP group during fasting and after feeding (98%+/- 1% vs 39%+/- 16%; P =.02, and 99%+/- 1% vs 43%+/- 18%; P =.03). The sites of luminal occlusions were intact in the URYJP group at 10 weeks. CONCLUSIONS: The combination of jejunal pouch and uncut Roux limb improved overall nutritional parameters when compared with the traditional Roux-en-Y, while preserving aboral propagation of jejunal pacesetter potentials.

Carcinoma of the parathyroid is a rare malignancy that can be cured surgically if the proper diagnosis and treatment is given initially. Arriving to the clinical suspicion of a malignancy preoperatively is by far the most important step for a good prognosis. Our goal is to review the correlation between clinical and final histopathological findings that can arouse the suspicion of such malignancy and their true predictive value in the diagnosis. All patients that underwent surgical removal of the parathyroid mass between March of 1992 and March of 2003 were reviewed retrospectively at Providence Hospital and Medical Centers. Among 168 patients who underwent parathyroid excision, 14 (8.3%) had hyperplasia of the parathyroid, 121 (72%) had benign adenoma, 25 (14.8%) had other benign lesions, and 8 (4.7%) patients had primary carcinoma of the parathyroid confirmed by pathology. Our mean serum calcium level was 11.57 mg/dL, which was lower than the mean level (12 mg/dL) for benign hyperparathyroidism. The mean tumor size was 2.18 cm, smaller than the proposed for malignant criteria, and none of the eight patients (0%) had any symptoms of hypercalcemia at the time of diagnosis. Seven of eight patients (87.5%) had frank signs of invasion together with other histological features, and two patients had associated papillary carcinoma of the thyroid. Five patients from our series did not meet clinical criteria for malignancy (tumor size > 3 cm, palpable mass, and serum calcium > 14 mg/dL), but had undisputable histological findings (high mitotic pattern, fibrous trabeculae, capsular invasion, vascular invasion, and nodular involvement). On the other hand, 17 patients with benign histology had tumors greater than 3 cm, and an additional 18 had palpable masses on physical examination. We believe that these patients need to be followed closely. The patients with diagnosis of parathyroid carcinoma, their kindred, and those with large adenomas may benefit from genetic screening for HRTP2 gene mutations in search of early detection of tumors suspicious for malignancy. This is based on the fact that we did not find correlation between the clinical presentation and the histological features in our patients with proven malignancy.

BACKGROUND: Interferons (IFNs) have antiproliferative effects on tumor cells. The apoptotic effects and sensitization to chemotherapy conferred by IFN therapy, however, are not clearly understood. The aims of the present study were to explore the apoptotic effects of IFNs in human pancreatic cancer cell lines and to attempt to define their ability to synergistically enhance sensitivity to 5-fluorouracil (5-FU) and gemcitabine, a mechanism that depends on the expression of IFN receptors. METHODS: Human pancreatic cancer cells were cultured alone or in combination with the chemotherapeutic agents 5-FU and gemcitabine. Differential dosages of IFN-alpha,-beta, and -gamma were also added to the cell lines concomitantly during a period of 24 to 96 hours. The cell line viability and effects of treatment were examined using the methylthiazol tetrazolium assay and single-stranded DNA apoptosis assay. The expression of IFN receptors was determined using immunohistochemistry. Caspase-8 inhibitor was used to block the caspase cascade. RESULTS: The antiproliferative and apoptotic effects of IFNs were most profoundly demonstrated on those cells that expressed the respective IFN receptor. The apoptotic effects provided by the interferons, however, were blocked by caspase-8 inhibition. The addition of IFNs significantly enhanced the cytotoxic effects of 5-FU and gemcitabine in those cell lines that expressed the corresponding IFN-alpha,-beta, or -gamma receptors. CONCLUSIONS: This study on pancreatic cancer cell lines has demonstrated that IFNs mediate apoptosis through IFN receptors and the caspase cascade. Enhanced cytotoxicity occurred when IFNs were combined with 5-FU and gemcitabine.

BACKGROUND: Gradually increased blood flow to the ischemic rat kidney was studied to assess the ability to diminish ischemia-reperfusion injury. METHODS: The left renal artery and vein were isolated in 25 rats. Microclamps were applied for 45 minutes and were released at once (group II) or gradually (group III). Renal arterial blood flow and K+ activity were measured. Bilateral kidneys were harvested for histopathology and for malonyldealdehyde and myeloperoxidase levels. RESULTS: Increased K+ activity returned to preischemic values faster in group III than in group II. No statistically significant difference existed in malonyldealdehyde and myeloperoxidase levels; histopathologic scoring showed less tissue damage in group III (P <.05). Contralateral kidney samples showed signs of ischemia in group II. CONCLUSIONS: Gradually increased blood flow to the ischemic kidney decreases ischemic changes. Ischemic insult to 1 kidney causes histopathologically detectable changes to the contralateral kidney, which can be diminished by gradual reperfusion.

Prevalence of Internet use indicates, that introducing internet to people with mental disorders might have a positive impact on their social integration. There are concerns about negative effects of dealing with virtual reality on the mental health of Internet users. AIM: Evaluation of the ICAR program--"Internet communication and active rehabilitation for people with mental disorders" concerning its utility in psychiatric rehabilitation. METHOD: 22 participants of the ICAR programme and 22 controls (people with mental disorders not participating in the programme) were investigated before and after the completion of the programme. There following were compared: their computer and Internet use skills, social functioning (Birchwood Scale), self-estimation of the mental health (Frankfurt Scale FBS), self-reported quality of life (WHO QOL BREV) and number of psychiatric hospitalisations during 11 months of the observation period. RESULTS: Among participants, their reported skills and motivation increased significantly following the programme. During 11 months of the observation there were less hospitalisations (1 fulltime and 1 daily) in the study group than in the control group (3 and 1). An increase of symptoms was observed in the Frankfurt Scale in 10 participants and 13 controls. The level of social functioning and severity of symptoms was not significantly different and did not change during observation. The self-reported quality of life increased in both groups during this period. CONCLUSIONS: ICAR training programme for the mentally ill, increases participants skills and motivation towards computer and Internet use, as well as their self-reported quality of life. The participation in the programme doesn't have any significant effect on the overall social functioning and number of psychiatric hospitalisations during the 11 months of observation. A positive effect of the ICAR programme on the quality of life, as well as some activating effect leading to exacerbation of the psychopatological symptoms--has an unspecific character and is therefore similar to the other community rehabilitation programmes. Wider spreading of computer training workshops similar to the ICAR programme might have a positive effect on social integration of people with mental disorders.

INTRODUCTION: The inguinal hemiotomy is a surgical procedure common in pediatric surgery and as in any operation the control of the pain is fundamental. The aim of this study is to verify the effect of the local anesthesia next to the general anesthesia, in the control of postsurgical pain. MATERIAL AND METHOD: A prospective study is made in 60 patients submitted for unilateral repair of hernia inguinal and hidrocele, under general anesthesia. The patients were designated at random in three equal groups after the anesthetic induction. In group I ilio-inguinal blockade is made, before the surgical incision. In group II local infiltration is made after the closing of the aponeurosis and in group III the anesthetic is not infiltrate. The age of the patients included was between 1 and 13 years. For the valuation of the pain and comparison between the three groups we used: 1) Measurements of conductual type. 2) Measurements of biological type before and after the intervention: Arterial tension, cardiac frequency, respiratory frequency... 3) Laboratory measurements: cortisol levels, prolactose, insulin and glucose. Two extractions are made, first after the anesthetic induction and second 60 minutes after the intervention. The results were analyzed using computer statistical program SPSS. A probability value of < 0,05 was considered significant. RESULTS: 1) Conductual measurements: the differences between groups I and II in relation to the III were significant. This conductual difference also was related to the age of the patients. 2) Measurements of biological type: in groups I and II the postoperative arterial tension average was smaller, but only in group I the difference was significant. The heart rate decreased in the three groups, but was significant only in group I, like the respiratory frequency. 3) Laboratory measurements: in groups I and II the levels of cortisol and glucose diminished in the postoperative period, but only in group I the difference was significant. The values of prolactose diminished in the postoperative period in group I but was not significant. Insulin experienced an increase in the three groups, although smaller in group I. CONCLUSIONS: 1) The results of the study demonstrate specially that the local infiltration of anesthetic diminishes the metabolic answer and reduces the intensity of the postoperating pain, when is made before the beginning of the surgery. 2) In the conductual answer to the pain not only influences the use of the anesthetics but the age of the patient.

An estimated 50% of all asthma patients do not take the medication as prescribed, i.e. are non-compliant. Numerous interventions have been done to improve patients' compliance have been evaluated in clinical studies, ranging from simple adjustments in the medication regimen to complex multidisciplinary interventions that address health system barriers and communication between patients and health care professionals. Beliefs or disbeliefs of health care professionals affect patients' compliance. Efforts to improve the adherence of physicians to asthma guidelines have been tested in numerous studies. Although several types of interventions are effective in improving compliance to medication for asthma, only a few indicated whether this success would actually result in clinical improvement. This review surveys the different options for enhancing compliance rates in patients with asthma.