Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

Neurocritical Care - For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral...     

Reduced concentration of hepatic alpha-tocopherol in patients with alcoholic liver cirrhosis.

The concentration of alpha-tocopherol was measured in liver biopsy specimens obtained from 83 patients with alcoholic and non-alcoholic liver diseases. The mean hepatic vitamin E content (as alpha-tocopherol) was significantly lower in 23 patients with alcoholic cirrhosis (17.6 +/- 12.1 nmol/mg wet weight liver), compared with 12 patients with normal liver histology (39.2 +/- 29.7 nmol/mg, P less than 0.01). The mean serum concentration of alpha-tocopherol was lower in patients with alcoholic cirrhosis (13.9 +/- 7.0 mumol/l) than in individuals with alcoholic fatty liver (21.3 +/- 9.3 mumol/l, P less than 0.01) and patients with normal liver histology (23.4 +/- 11.6 mumol/l, P less than 0.01). A decreased ratio of serum alpha-tocopherol/total serum lipids was also observed in patients with alcoholic cirrhosis, compared with patients with normal liver histology (P less than 0.05). There was a significant correlation between concentrations of alpha-tocopherol in liver and serum (r = 0.43, P less than 0.001). Furthermore, serum alpha-tocopherol correlated with retinol (r = 0.53, P less than 0.001), selenium (r = 0.45, P less than 0.001), and albumin (r = 0.37, P less than 0.001) in serum. We suggest that the reduced content of hepatic alpha-tocopherol observed in some patients may play a role in ethanol-induced lipid peroxidation.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Neural classifier construction using regularization, pruning and test error estimation

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.     

Mode of delivery and risk of allergic rhinitis and asthma

BACKGROUND: It has been hypothesized that cesarean section might increase the risk of developing allergic disease by depriving the fetus and newborn of exposure to maternal microflora. Furthermore, it has been suggested that complicated modes of delivery might be associated with an increased risk of asthma. OBJECTIVE: The purpose of this investigation was to study whether cesarean section and other complicated modes of delivery are associated with an increased risk of allergic rhinitis or asthma. METHODS: Information on self-reported allergic rhinitis, asthma ever, current asthma, and occupation was obtained from 9722 singleton women born in Denmark during the period 1973-1977 who participated in a national cohort study during the period 1997-2001. For these women, information was available on mode of delivery (spontaneous delivery, cesarean section, vacuum extraction, or other complicated mode of delivery, such as rotation/traction or use of forceps), gestational age, birth weight, and length at birth from the Danish Medical Birth Register. Information on parity and maternal age was obtained from the Danish Civil Registration System. RESULTS: The odds ratios (ORs) of allergic rhinitis were 1.16 (95% CI, 0.90-1.49) for cesarean section and 1.06 (95% CI, 0.85-1.32) for other complicated modes of delivery in comparison with spontaneous delivery. The corresponding ORs of asthma ever were 1.33 (95% CI, 1.02-1.74) and 1.18 (95% CI, 0.94-1.49) for cesarean section and other complicated modes of delivery, respectively, and the ORs of current asthma were 1.22 (95% CI, 0.87-1.73) and 1.26 (95% CI, 0.94-1.68), respectively, in comparison with spontaneous delivery. CONCLUSIONS: Our findings do not support the hypothesis that cesarean section or other complicated modes of delivery are associated with the development of allergic rhinitis. However, there might be a positive association with development of asthma--in particular, for cesarean section--that was not explained by gestational age, birth weight, ponderal index, smallness for gestational age, parity, maternal age, or occupation.     

Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms

Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy, little is known about the role of other Hsp70 proteins in cancer. Here we present the first thorough analysis of the expression and function of the cytosolic Hsp70 proteins in human cancer cells and identify Hsp70-2, a protein essential for spermatogenesis, as an important regulator of cancer cell growth. Targeted knock-down of the individual family members by RNA interference revealed that both Hsp70 and Hsp70-2 were required for cancer cell growth, whereas the survival of tumorigenic as well as nontumorigenic cells depended on Hsc70. Cancer cells depleted for Hsp70 and Hsp70-2 displayed strikingly different morphologies (detached and round vs. flat senescent-like), cell cycle distributions (G2/M vs. G1 arrest) and gene expression profiles. Only Hsp70-2 depletion induced the expression of macrophage inhibitory cytokine-1 that was identified as a target of P53 tumor-suppressor protein and a mediator of the G1 arrest and the senescent phenotype. Importantly, concomitant depletion of Hsp70 and Hsp70-2 had a synergistic antiproliferative effect on cancer cells. Thus, highly homologous Hsp70 proteins bring about nonoverlapping functions essential for cell growth and survival.