Impaired fatty acid oxidation in children on valproic acid and the effect of L-carnitine

Fatty acid oxidation was studied in 12 patients (aged 3 to 19 years) receiving valproic acid (VPA), predominantly as monotherapy, before and after 1 month of L-carnitine supplementation (50 mg/kg/day po) in order to determine whether L-carnitine plays a role in preventing the hepatotoxic effects of this drug. Five of these patients were also studied prior to VPA treatment. Only one patient taking VPA had an abnormally low plasma free carnitine. Acyl-/free carnitine ratios were elevated in five patients on VPA and normalized after L-carnitine supplementation. Mean plasma concentrations of free fatty acids, beta-OH-butyrate, and cumulative excretion of 13CO2 after administration of 1-13C-octanoic acid were not changed by VPA or L-carnitine treatment. Urinary dicarboxylic acids, acylglycines, and octanoylcarnitine were elevated during VPA therapy and unaltered by L-carnitine. These results suggest that, in patients at low risk for VPA-induced hepatotoxicity (patients aged > 2 years and taking VPA as monotherapy), VPA causes metabolic abnormalities resembling those found in inborn errors of mitochondrial beta-oxidation which are not corrected by L-carnitine.     

Cerebral edema, mass effects, and regional blood volume in man

The relation between directly measured arterial blood pressure and blood volume was studied in 61 sick preterm infants. Mean blood volume (derived from plasma volume [T1824 ten-minute albumin space] and hematocrit value) of 26 hypotensive infants (89.1 +/- 17.26 ml/kg) was not significantly different from that of 35 normotensive, but otherwise comparable, infants (91.4 +/- 14.57 ml/kg). There was no relation between arterial mean blood pressure and blood volume. Twenty-one infants with arterial mean blood pressure less than 30 mm Hg were given 1.0 g/kg of 10% salt-poor albumin. Significant increases in blood pressure occurred but were small in magnitude; more than one half of infants had arterial mean blood pressures persistently less than 30 mm Hg. Arterial/alveolar PO2 ratio decreased significantly with albumin infusion in six infants with hyaline membrane disease not receiving continuous distending-airway pressure, suggesting an association between infused albumin and impaired oxygen exchange.     

Sarcomas in organ allograft recipients

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.     

Damage to cereals caused by decaying weed residues

Poor establishment and growth of a succeeding crop has on some isolated occasions been observed after glyphosate has been used to kill dense infestations of couch (quack) grass. It appears that damage is caused by toxins and pathogens from the decaying weed residues rather than by the herbicide or its metabolites.     

MHC-disassortative mating preferences reversed by cross-fostering

House mice (Mus musculus domesticus) avoid mating with individuals that are genetically similar at the major histocompatibility complex (MHC). Mice are able recognize MHC-similar individuals through specific odour cues. However, to mate disassortatively for MHC genes, individuals must have a referent, either themselves (self-inspection) or close kin (familial imprinting), with which to compare the MHC identity of potential mates. Although studies on MHC-dependent mating preferences often assume that individuals use self-inspection, laboratory experiments with male mice indicate that they use familial imprinting, i.e. males learn the MHC identity of their family and then avoid mating with females carrying 'familial' MHC alleles. To determine if female mice use familial imprinting, we cross-fostered wild-derived female mouse pups into MHC-dissimilar families, and then tested if this procedure reversed their mating preferences compared with in-fostered controls. Our observations of the female's mating behaviour in seminatural social conditions and the genetic typing of their progeny both indicated that females avoided mating with males carrying MHC genes of their foster family, supporting the familial imprinting hypothesis. We show that MHC-dependent familial imprinting potentially provides a more effective mechanism for avoiding kin matings and reducing inbreeding than self-inspection.     

Information processing, social skill, and gender in schizophrenia

The relationships among information processing, social skill, and gender in individuals with chronic schizophrenia were investigated. Although there were no gender differences in information processing, social skill, or negative symptoms, performance on information-processing tasks was related to various indices of social skill (e.g., paralinguistic skill) for female, but not male, inpatients. This pattern of results remained after statistical controls were applied for age, illness chronicity, and positive symptoms.     

Rape flashbacks: constructing a new narrative

1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, whereas oxidative stress by the radiation can cause cellular responses to defense cellular injury. In this study, the metabolism of antioxidants in response to ionizing radiation to the brain was studied in the brain using experimental rabbits. 2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activity of a GSH synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes were dependent on the radiation dose. 3. Previous intrathecal-administration of buthionine sulfoximine (100 microM), a specific inhibitor of gamma-GCS, increased DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation. 4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to ionizing radiation and this induction of antioxidants may play a role in reducing tissue damage in radiotherapy.     

Validation by Monte Carlo sampling of experimental observation functionals

We present and analyze a validation procedure for a given state estimate u ^? of the true field u ^true based on Monte Carlo sampling of experimental observation functionals. Our method provides, given a set of N possibly noisy local experimental observation functionals over the spatial domain Ω, confidence intervals for the L ²(Ω) error in state and the error in L ²(Ω) outputs. For L ²(Ω) outputs, our approach also provides a confidence interval for the output itself, which can be used to improve the initial output estimate based on u ^?. Our approach implicitly takes advantage of variance reduction, through the proximity of u ^? to u ^true, to provide tight confidence intervals even for modest values of N . We present results for a synthetic model problem to illustrate the elements of the methodology and confirm the numerical properties suggested by the theory. Finally, we consider an experimental thermal patch configuration to demonstrate the applicability of our approach to real physical systems.