Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels in an animal model of mania

It has been demonstrated that lithium (Li) and valproate (VPT), first line mood stabilizers, increase BDNF content in rat hippocampus and frontal cortex, which suggests that the regulation of neurotrophic factors might be associated with their pharmacological effects. In sight of the scarcity of studies with other neurotrophins, and the possible relevance of multiple neurotrophic signaling systems in bipolar disorder we investigated the effects of Li and VPT on NT-3 levels in rat serum and hippocampus, using an animal model of mania induced by amphetamine (AMPH). In the reversal model, adult male Wistar rats received AMPH or saline for 14 days, and between the 8th and 14th days, animals were treated with Li, VPT or saline. In the prevention model, rats were pretreated with Li, VPT or saline, and between the 8th and 14th days, the animals received AMPH or saline. Li increased serum and hippocampal NT-3 levels in all conditions, whereas VPT increased hippocampal NT-3 in the prevention model only. Li reversed AMPH changes in NT-3 in the reversal model, and VPT prevented AMPH changes in NT-3 in the prevention model. These results suggest that both Li and VPT modulate serum and central (hippocampal) NT-3 levels, and further support that the regulation of neurotrophic signaling systems may be related to the mechanisms of action of mood stabilizers.     

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn

Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old.     

Peritoneal dialysis in neonates with inborn errors of metabolism: is it really out of date?

Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of metabolism to minimize the effects of the acute accumulation of neurotoxic metabolites that can produce irreversible and severe neurological damage and even death. In recent papers, extracorporeal dialysis has been described as more effective than peritoneal dialysis in improving the prognosis in newborns with inborn errors of metabolism and hyperammonemia. However, it appears that the outcome is primarily related to the duration of neonatal hyperammonemic coma. Here we report seven newborns with hyperammonemia caused by inborn errors of metabolism (five with organic acidemias, two with urea-cycle disorders). They received dietetic and pharmacological treatment as well as peritoneal dialysis. Four of the five patients with organic acidemia survived with and without mild neurological impairment (follow-up 3.5–10 years). One died from bacterial sepsis after peritoneal dialysis was discontinued and the peritoneal catheter was removed. One of the two patients affected by urea-cycle disorders, a boy, died during the neonatal period, and the other, a girl, died at the age of 13 months due to severe neurological damage. Our results demonstrate that peritoneal dialysis may still be an effective treatment for neonatal hyperammonemia caused by inborn errors of metabolism. Furthermore, peritoneal dialysis can be administered quickly and easily in all settings, clearly an advantage when fast intervention is so crucial.     

Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series

OBJECTIVE: Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression. METHODS: Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted. RESULTS: Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 mumol/L to 11 mumol/L (P= 0.001), and ALT from 97 IU/L to 39 IU/L (P= 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well. CONCLUSIONS: Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.     

Is the “10% Rule” Equally Valid for All Subsets of Sentinel-Node-Positive Breast Cancer Patients?

Background  In breast cancer, a combination of radioisotope and blue dye mapping maximizes the success and accuracy of sentinel node (SLN) biopsy. When multiple radioactive nodes are present, there is no single definition of isotope success, but the popular “10% rule” dictates removal of all SLN with counts >10% of the most radioactive node. Here we determine how frequently a positive SLN would be missed by the 10% rule. Methods  Between 9/96 and 12/04, we performed 6,369 successful SLN biopsies using ^99mTc sulfur colloid and isosulfan blue dye, removing as SLN all radioactive and/or blue nodes, and taking counts from each node ex vivo. Standard processing of all SLNs with a benign frozen section included hematoxylin and eosin (H&E) staining, serial sectioning, and immunohistochemistry (IHC). Results  33% of patients (2,130/6,369) had positive SLNs. Of these patients, 1,387/2,130 (65%) had >1 SLN identified. The most radioactive SLN was benign in 29% (398/1,387), and 107/1,387 (8%) had a positive SLN that was neither blue nor the hottest. From this group 1.7% (24/1387) of patients had positive SLN with counts <10% radioactive counts of the hottest node. The 10% rule captured 98.3% of positive nodes in patients with multiple SLNs. No patient characteristics were predictive of failure of the 10% rule. Conclusion  With combined isotope and blue dye mapping, the 10% rule is a robust guideline and fails to identify only 1.7% (24/1387) of all SLN-positive patients with multiple SLNs. This guideline appears to be equally valid for all subsets of patients.     

Coronary angiography following acute myocardial infarction in Ontario, Canada

BACKGROUND: The role of scientific evidence in shaping recommendations on capacity targets and cardiovascular technology utilization is unclear. METHODS: The temporal growth in the use of coronary angiography services and the use of statins after an acute myocardial infarction (AMI) was determined for all patients older than 65 years admitted to any hospital in Ontario, Canada, between 1992 and 2004. A Bayesian change-point regression model was used to determine the rate of maximum uptake (inflection point) for use of cardiac catheterization service and statins after AMI. The inflection points were compared with the corresponding publication dates of the first positive evidence for outcome efficacy of use of cardiac catheterization service and statins after AMI as obtained from randomized control trials. RESULTS: The use of post-AMI coronary angiography closely mirrored overall temporal increases in cardiac catheterization capacity between 1992 and 2004 (r = 0.95, P<.001). The inflection point for post-AMI angiography service use was September 1998, 11 months before the publication of the first positive randomized controlled trial demonstrating benefit of routine post-AMI angiography. Conversely, the inflection point for statin therapy occurred in October 1998, 47 months after the publication of the first positive randomized controlled trial demonstrating the benefits of statin therapy for the secondary prevention of coronary artery disease. These findings were consistent regardless of the presence of on-site cardiac catheterization facilities at the admitting AMI institution and patient illness severity levels. CONCLUSION: The proliferation of cardiac catheterization in Ontario is attributable to factors other than the emergence of published scientific evidence.