Mineralo- and glucocorticoid receptor mrnas are differently regulated by corticosterone in the rat hippocampus and anterior pituitary

In most cell lines and animal tissues, glucocorticoid receptors undergo downregulation after exposure to corticosterone. However, corticosterone treatment has not shown a consistent effect on mineralocorticoid (MR) and glucocorticoid receptors (GR) in the hippocampus, and it has been rarely assessed in the anterior pituitary. In this study we investigated dose-dependent effects of corticosterone on MR and GR mRNAs in the hippocampus and anterior pituitary. Adrenalectomized rats substituted with corticosterone in drinking fluid were injected subcutaneously with vehicle or 1, 10, 50, 100, or 200 mg of corticosterone, and sacrificed 4 h later. In the hippocampus we found a progressive decrease in MR and GR mRNAs with increasing doses of corticosterone. This was significant with 50 and 100 mg corticosterone for MR mRNA and with 10-200 mg corticosterone for GR mRNA at plasma corticosterone levels above 30 microg/dl. The anterior pituitary did not show significant changes at any dose. A time-course with 2 mg of corticosterone (non-response dose range at 4 h) revealed a significant decrease in MR and GR mRNAs in the hippocampus 8 h after the subcutaneous injection. In the anterior pituitary both mRNAs showed an increase that was significant 24 h after injection for MR and from 8 to 24 h for GR. In the hippocampus, adrenalectomy (absence of corticosterone) induced a significant increase in MR and GR mRNAs on day 3, but not on days 1, 8 and 21 after adrenalectomy. In the anterior pituitary there were no significant changes at any time after adrenalectomy. In summary, we have found an in vivo corticosterone dose- and time-dependent downregulation of MR and GR mRNAs in the hippocampus, whereas anterior pituitary MRs and GRs seem relatively insensitive to the excess or the absence of corticosterone, suggesting the lack of an autoregulatory effect in this tissue. Significant mRNA changes appearing later in time could suggest a secondary response via a glucocorticoid-induced gene product. Corticosteroid receptor downregulation in the hippocampus could prevent overstimulation or tissue damage when plasma corticosterone is high, while increased corticosteroid receptors in the anterior pituitary could buffer the excessive brain drive on the pituitary during chronic stress or pathological conditions associated with increased plasma glucocorticoids, such as depression.     

Pancreatic arteriovenous malformation

We report a case of a 57-year-old male with a pancreatic arteriovenous malformation (AVM). The diagnosis was made by CT scan and angiography. In the reported case, bleeding from AVM into the biliary tract caused haemobilia and bleeding into the pancreatic head caused abdominal pain. Pancreatic AVM has been only rarely reported as a cause of haemobilia.     

Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia

Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia. It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors. The long-term efficacy and safety of aripiprazole (30 mg/d) relative to haloperidol (10 mg/d) were investigated in two 52-wk, randomized, double-blind, multicentre studies (using similar protocols which were prospectively identified to be pooled for analysis) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications. Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures, including significantly greater improvements for PANSS negative subscale scores and MADRS total score (p<0.05). The time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol (p=0.0001). Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol (p=0.0001). Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessments than haloperidol (p<0.001). In summary, aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability. Aripiprazole represents a promising new option for the long-term treatment of schizophrenia.     

Outbreak of invasive aspergillosis among renal transplant recipients

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA. IA was defined using established guidelines. Four IA cases occurred among 40 RTRs hospitalized during the study period. Factors associated with an increased risk of IA included prolonged hemodialysis, lengthy corticosteroid treatment posttransplant, and use of sirolimus alone or with mycophenolate (P<0.05). After the study period, three additional RTRs developed IA; two Aspergillus isolates recovered from these patients had indistinguishable profiles by DNA fingerprinting, suggesting common-source exposure. This study suggests that immunosuppressed RTRs can be at an increased risk for IA. Measures to prevent IA in these patients should be taken during hospital construction.     

Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. PATIENTS AND METHODS: A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n=17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. RESULTS: The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P<0.001). All CRCs in the PSC group were in patients with IBD and an intact colon. The cumulative risk of developing CRC in the 83 patients with an intact colon and IBD was 14% and 17% after 5 and 10 years, respectively (PSC non-IBD group 0% risk after 10 years, P<0.06). The multivariate analysis showed three significant variables related to the risk of developing CRC: colonic dysplasia after LT (P<0.0003), duration of colitis more than 10 years (P<0.002), and pancolitis (P<0.004). The cause of death in patients with CRC was cancer related in 75% of cases with a reduced 5-year survival of 55% versus 75% without CRC (not significant). CONCLUSION: Patients with PSC undergoing LT with a long history of ulcerative colitis and pancolitis have an increased risk of developing CRC with reduced survival. We advocate long-term aggressive colonic surveillance and colectomy in selected high-risk patients with longstanding severe colitis.     

New perspective for the management of near-total or total intestinal aganglionosis in infants

Background Purpose: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis. Methods: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II). Results. Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6). Conclusions: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease. J Pediatr Surg 38:25-28.     

Hepatic-artery aneurysm in adult liver transplantation

Hepatic artery aneurysm (HAA) is a rare vascular complication, but has a high mortality rate in liver transplant recipients. This study reports the precipitating factors, clinical manifestation, pre-operative diagnosis, related micro-organism, management, and outcome, in a series of HAAs that developed after adult orthotopic liver transplantation (OLT). Data on the primary disease as well as on the above were obtained from a prospective database, and all case records were reviewed. There were eight (0.5%) HAAs in 1,575 adult cadaveric OLTs between 1982 and March 2001. All were pseudo-aneurysms around the native hepatic-artery (HA) anastomosis, and all occurred in whole-organ OLTs. There were three types of clinical presentations: sudden hypotension (n=4), gastrointestinal (GI) bleeding (n=2), and abnormal liver-function tests (LFTs) (n=2). The majority (n=7) presented within the first 2 months (median: 27.5 days, range: 12-760 days) following OLT. A pre-operative diagnosis of HAA was not determined in five cases. The sensitivity of abdominal ultrasound scan (USS), computed tomography (CT) scan and angiography for detection of HAAs was 3 of 5, 1 of 2 and 3 of 4, respectively. Micro-organisms could be identified in six patients (bacteria n=4 and fungi n=3). All patients underwent urgent operations (excision of HAA in six and ligation in two cases). Immediate reconstruction of the HA was carried out, two different methods being used: repair of native arteries (n=2) and arterial conduit (interposition n=3 and aortic conduit n=2). Two patients died peri-operatively, two died within 2 months, and the remaining four patients are alive at between 8.6 and 12.8 years after repair. HAA following OLT is unpredictable in its presentation, and the sensitivity of clinical and radiological detection is low. A high index of suspicion is required, and urgent surgery with immediate re-vascularisation and use of appropriate antibiotic/anti-fungal agents is recommended.