Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

Tumor-associated glycoprotein-72 serum levels complement carcinoembryonic antigen levels in monitoring patients with gastrointestinal carcinoma. A longitudinal study

Eighty-two patients diagnosed with gastrointestinal (GI) adenocarcinoma were evaluated before and for 26 months after primary tumor resection for the presence of two serum tumor markers: tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA). Elevated TAG-72 and CEA serum levels were found preoperatively in 32 (39%) and 34 (41.5%) of the 82 patients, respectively. The percentage of patients with elevated serum levels of either TAG-72 or CEA was 56.1% (46 of 82). Twelve (15%) patients who had normal CEA serum levels had elevated TAG-72 serum levels, and conversely, serum from 14 (17%) patients who were TAG-72 negative were CEA positive. Forty-five of the 82 patients were diagnosed with advanced disease (i.e., Stages C and D for colorectal, Stages III and IV for stomach), and 29 (64.4%) and 26 (57.8%) of those patients had elevated serum levels of TAG-72 or CEA, respectively. Elevated levels of either TAG-72 or CEA, however, were found in sera of 82.2% of patients with advanced GI cancer, which is an increase of 24.4% over the use of CEA antigen alone as a marker of disease. The measurement of both TAG-72 and CEA may improve the diagnosis of patients with GI malignant disease due to the apparent complementary association which exists between these tumor markers. Serum TAG-72 and CEA levels were monitored in 31 patients for varying lengths of time after resection of the carcinoma; 11 patients developed recurrent disease. Sera from nine of 11 (81.8%) of these patients had elevated TAG-72 levels and six of 11 (54.5%) had elevated CEA levels. Tumor marker elevations were observed either before (35 to 166 days) or at the time of diagnosis of recurrence. The elevation of one or both markers correlated with the clinical status in ten of 11 (90.9%) patients with recurrence. In addition, 20 patients who were clinically free of disease after more than 700 days' follow-up had normal serum levels of both TAG-72 and CEA. These findings suggest that the combined use of serum TAG-72 and CEA measurements may improve detection of recurrence in patients with GI cancer and may be useful in the postsurgical management of GI adenocarcinoma patients.     

Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats

Brain androgen binding and metabolism, serum testosterone (T), and sexual behavior were measured in old and young male Fischer 344 rats. After completion of sexual behavior tests, blood was collected for T assay and brains were removed for simultaneous measurements of cytosolic (ARc) and nuclear (ARn) androgen receptors and aromatase activity (AA) in the preoptic area (POA), hypothalamus (HYP) and amygdala (AMG). In Experiment 1, old and young intact males were examined. None of the old males ejaculated in any of the tests of sexual behavior whereas all of the young males ejaculated. The old males had lower levels of serum T, lower levels of ARn in the POA and HYP and lower levels of AA in the POA. The ARc levels of the old and young males did not differ. Experiment 2 was designed to determine if the deficits in brain androgen binding and metabolism were due to low levels of T. Old and young T-treated gonadectomized (GX-T) males and young intact (I) males were examined. T levels were comparable in the young and old GX-T males and were higher in each of these groups than in the young I males. In sexual behavior tests, all of the young but only 25% of the old GX-T males ejaculated. Although ARn levels in the old GX-T males were lower than in the young GX-T males, they were comparable to the young I male levels. No age-related differences in T induction of AA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease.

OBJECTIVE: To reduce antiparkinsonian medication in parkinsonian patients with bilateral high frequency subthalamic nucleus (STN) stimulation. BACKGROUND: Parkinsonian syndromes are characterized by hyperactivity of the STN. Preliminary data indicate that functional inactivation of the STN may reduce the requirement for dopaminergic therapy in PD. METHODS: Bilateral quadripolar leads were implanted stereotactically in the STN of seven patients with advanced PD (mean age, 57.4 years; mean disease duration, 15.4 years). High-frequency stimulation was applied for 24 hours a day. Following implantation, antiparkinsonian medication was reduced to the minimum possible and stimulation was gradually increased. The patients were evaluated in the practically defined "off" and "on" conditions using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England scale. The average follow-up was 16.3+/-7.6 months. A battery of neuropsychological tests was applied before and 9 months after the implant. RESULTS: Parkinsonian features improved in all patients--the greatest change seen in rigidity, then tremor, followed by bradykinesia. Compared with the presurgical condition, off-drug UPDRS motor scores improved by 41.9% on the last visit (p = 0.0002), UPDRS activities of daily living (ADL) scores improved by 52.2% (p = 0.0002), and the Schwab & England scale score improved by 213% (p = 0.0002). The levodopa-equivalent daily dose was reduced by 65%. Night sleep improved in all patients due to increased mobility at night, and in five patients insomnia was resolved. All patients gained weight after surgery and their appetite increased. The mean weight gain at the last follow-up was 13% compared with before surgery. During the last visit, the stimulation amplitude was 2.9+/-0.5 V and the total energy delivered per patient averaged 2.7+/-1.4 W x10(-6). The results of patient self-assessment scales indicated a marked improvement in five patients and a moderate improvement in the other two. The neuropsychological data showed no changes. Side effects were mild and tolerable. In all cases, a tradeoff between the optimal voltage and the severity of side effects made it possible to control parkinsonian signs effectively. The most marked side effects directly related to STN stimulation consisted of ballistic or choreic dyskinesias of the neck and the limbs elicited by contralateral STN stimulation above a given threshold voltage, which varied depending on the individual. CONCLUSIONS: Parkinsonian signs can be controlled by bilateral high-frequency STN stimulation. The procedure is well tolerated. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medication. Bilateral high-frequency STN stimulation compensated for drug reduction and elicited dyskinesias, which differ from those observed following dopaminergic medication. ADL improved significantly, suggesting that some motor tasks performed during everyday chores, and that are not taken into account in the UPDRS motor score, also improved.     

Soluble CD40 ligand plasma levels in lung cancer.

PURPOSE: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.     

Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression on brain microvascular endothelial cell (BMEC) culture. The tyrosine kinase (TK) inhibitor genestein (100 microgram/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta-1a (1000 U/ml) antagonized TNFalpha effect. When an ineffective dose of IFbeta-1a (100 U/ml) was challenged with ineffective doses of either genestein (10 microgram/ml) or staurosporin (0.1 nM), the combination IFbeta-1a-genestein significantly reduced TNFalpha-induced ICAM1 expression whereas IFbeta-1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNFalpha response by IFbeta-1a on BMECs.     

Adaptation of the Youth Connectedness to Provider scale to assess the relationship between health professionals and adolescent and young adult patients

ObjectiveThe aim was to adapt an instrument that evaluates the relationship between young individuals and health professionals to the Brazilian population, which will be called the Escala de Avaliação de Vínculo entre Jovens e Profissionais de Saúde (Youth Connectedness to Provider scale).MethodThe questionnaire known as the Youth Connectedness to Provider scale consists of seven Likert-like questions. The translation, back-translation, evaluation by ten specialists, and pre-test with 43 adolescents and young adults aged between 10 and 24 years were performed to assess the clarity and reliability of meanings. The content validity index was calculated for each question. Subsequently, the clinical validation was performed with 83 patients aged 10–24 years old and Cronbach's alpha coefficient was calculated.ResultsA content validity index >0.8 (considered satisfactory) was obtained for all items analyzed by experts and adolescents. At the clinical validation, it showed a high internal consistency (Cronbach’s alpha = 0.76). The questions showed a good correlation, except for the question about judgment (Spearman’s rho = 0.03–0.19).ConclusionsThe scale adaptation showed an adequate agreement rate at the translation evaluation and a good reliability index in the questions. This instrument provides information on strengths and topics that require more attention from professionals to improve the relationship with their patients; it can be a valuable parameter in assessing the medical consultation quality.