Use of oxygen therapy for pneumocephalus: a systematic review.

Pneumocephalus is the pathologic collection of air in the intracranial cavity. In sufficient volumes, it can contribute to symptoms ranging from headaches to death. For conservative treatment, oxygen use is commonplace. Although this is an accepted tenet of clinical practice, it is not necessarily founded on robust trials. An electronic search of databases EMBASE and MEDLINE and the Cochrane Library was undertaken as per the 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Three articles were included. Although the modes of oxygen delivery were heterogenous (non-rebreather versus endotracheal versus hyperbaric chamber), all studies concluded favorably on the use of oxygen therapy for increased reabsorption of pneumocephalus.

Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.

Neurexin 1 (NRXN1), a presynaptic cell adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including autism, intellectual disability and schizophrenia. To gain insight into NRXN1's involvement in human cortical development we used quantitative real-time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms, NRXN1-α and NRXN1-ß, in prefrontal cortex from fetal stages to aging. In addition, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison with non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, markedly increasing with gestational age. In the postnatal dorsolateral prefrontal cortex, expression levels were negatively correlated with age, peaking at birth until ~3 years of age, after which levels declined markedly to be stable across the lifespan. NRXN1-ß expression was modestly but significantly elevated in the brains of patients with schizophrenia compared with non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human dorsolateral prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders.

Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain.

Neuregulin-1 (NRG-1) plays important roles in the development and plasticity of the brain, and it has recently been identified as a susceptibility gene for schizophrenia. Though there are rodent data, little is known about its distribution in the human brain. The aim of this study was to ascertain the localization of NRG-1 and its mRNA in multiple regions of the normal adult human brain. We investigated NRG-1 mRNA in 11 subjects using in situ hybridization and northern analysis, and NRG-1 protein in six subjects using immunohistochemistry and Western blotting. NRG-1 mRNA was present as bands of approximately 2, 3 and 6 kb. It was clearly detected in the prefrontal cortex (middle laminae), hippocampal formation (except CA1), cerebellum, oculomotor nucleus, superior colliculus, red nucleus and substantia nigra pars compacta. At the cellular level, NRG1 mRNA was abundant in hippocampal and cortical pyramidal neurons and some interneurons, and in cerebellar Purkinje cells and Golgi cells. NRG-1 protein was detected as bands of approximately 140, 110, 95 and 60 kD. Immunohistochemistry revealed NRG-1 in many cell populations, consistent with the mRNA data, being prominent in pyramidal neurons, Purkinje cells, several brainstem nuclei, and white matter neurons. Moderate NRG-1 immunoreactivity was also observed in cerebellar and dentate gyrus granule cells, and some glia. Within neurons, NRG-1 staining was primarily somatodendritic; in the cell body staining was granular, with clustering close to the plasma and nuclear membranes. There was also labeling of some fiber tracts, and local areas of neuropil (e.g. in the dentate nucleus) suggestive of a pre-synaptic location of NRG-1. The data show a widespread expression of NRG-1 in the adult human brain, including, but not limited to, brain areas and cell populations implicated in schizophrenia. Using these normative data, future studies can ascertain whether the role of NRG-1 in the disease is mediated, or accompanied, via alterations in its expression.

The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology.

The neuropathological features of schizophrenia are suggestive of a developmentally induced impairment of synaptic connectivity. Semaphorin 3A (sema3A) might contribute to this process because it is a secreted chemorepellant which regulates axonal guidance. We have investigated sema3A in the cerebellum (an area in which expression persists in adulthood), and measured its abundance in 16 patients with schizophrenia and 16 controls. In adults, sema3A was predominantly localized to the inner part of the molecular layer neuropil, whereas infants and rats showed greater labelling of Purkinje cell bodies. Sema3A was increased in schizophrenia, as shown by enzyme-linked immunosorbent assay (+28%; P<0.05) and immunohistochemistry (+45%; P<0.01). We also measured reelin mRNA, since reelin is involved in related developmental processes and is decreased in other brain regions in schizophrenia. Reelin mRNA showed a trend reduction in the subjects with schizophrenia (-26%; P=0.07) and, notably, was negatively correlated with sema3A. Sema3A also correlated negatively with synaptophysin and complexin II mRNAs. The results show that sema3A is elevated in schizophrenia, and is associated with downregulation of genes involved in synaptic formation and maintenance. In this respect, sema3A appears to contribute to the synaptic pathology of schizophrenia, perhaps via ongoing effects of persistent sema3A elevation on synaptic plasticity. The findings are consistent with an early neurodevelopmental origin for the disorder, and the reciprocal changes in sema3A and reelin may be indicative of a pathogenic mechanism that affects the balance between trophic and inhibitory factors regulating synaptogenesis.

Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses.

The psychotomimetic properties of NMDA glutamate receptor antagonists suggest there may be disease related changes of this receptor in schizophrenia. Using in situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of hippocampus from schizophrenics, depressives, bipolar patients and normal controls. A significant main effect of diagnosis was observed in the dentate gyrus (ANOVA, p = 0.004) and a trend in the CA3 region (ANOVA, p = 0.06), with all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal controls. In contrast to the affectively ill groups, the reductions in schizophrenics were more pronounced in the left side compared to the right. Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in schizophrenia but reductions in NMDAR1 remained significant when expressed as a ratio of poly A. The findings confirm a recent report of reduced hippocampal NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a feature of both affective and schizophrenic disorders and that schizophrenia is distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene expression.

Stereotactic radiosurgery in New Zealand.

AIMS: To explain the use of Stereotactic Radiosurgery for intracranial lesions and report Dunedin Hospital's early experience with this treatment. METHODS: Review of a prospective computer database and departmental clinical files. RESULTS: 74 patients underwent 78 radiosurgical procedures between 30 July 1994 to 18 December 1997. 28 patients with arteriovenous malformations were treated with an obliteration rate of 82% (95% CI: 48% to 98%) at two years. Seventeen vestibular schwannomas (acoustic neuroma's) were treated, with follow-up magnetic resonance imaging available in eleven in whom there was no tumour progression after a mean period of twelve months. There was preservation of some hearing in all patients not already deaf, but one developed a new facial palsy and another had worsening palsy as late side effects. Other tumours, including selected metastases, gliomas and skull base tumours have been treated in smaller numbers. CONCLUSION: Rates of arteriovenous malformation obliteration, vestibular schwannoma control, and side effects of radiosurgery in Dunedin are comparable to those reported in other uncontrolled series. Radiosurgery is quick and has a low procedure-related morbidity but does have important limitations and delayed side effects, which means the decision to treat needs to be based on thorough multidisciplinary review.

Longitudinal study of daily intake and excretion of lead in newly born infants.

As an adjunct to a study of lead mobilization during pregnancy and lactation, we have obtained estimates of the daily lead intake and excretion/intake for 15 newly born infants monitored for at least 6 months postpartum. The longitudinal data presented reflect the far lower levels of environmental contribution to lead in blood in the 1990's than that in the earlier studies from the 1970's and early 1980's, the last period for which such dietary information is available in newly born infants. Infants were breast-fed or formula-fed or both and, in the second quarter, were usually fed solid foods (beikost). Lead concentrations were as follows: lead in breast milk, ranged from 0.09 to 3.1 microg/kg with a geometric mean of 0.55 microg/kg, lead in infant formula ranged from 0.07 to 11.4 microg/kg with a geometric mean of 1.6 microg/kg, and lead in beikost ranged from 1.1 to 27 microg/kg with a geometric mean of 2.9 microg/kg. Daily lead intakes ranged from 0.04 to 0.83 microg/kg body weight/day with a geometric mean of 0.23 microg Pb/kg body weight/day, and excretion/intake ranged from 0.7 to 22 with a geometric mean of 2.6. There was no significant difference at the 5% level in lead concentration in daily intakes and excretion/intake for the first quarter versus the second quarter for this small number of subjects. Assuming that there was no contribution from environmental samples such as house dust and ambient air, the contribution of diet to blood has been estimated from lead isotopic measurements with the following ranges: for breast milk only as the dietary source, 40 to 65%; for breast milk and infant formula as the dietary sources, 15 to 70%; and for infant formula and beikost, 20 to 80%. The geometric mean value of the dietary contribution to blood over the 6-month period of approximately 35% is consistent with earlier estimates of uptake of lead in blood in newly born infants when environmental lead concentrations were much higher. Other sources such as air, soil, and dust are considered to contribute minimally to blood lead in these infants because of the low 206Pb/204Pb ratios in environmental media. Thus, we consider that the increased excretion over intake, along with other evidence, reflects mobilization of infant tissues arising especially from rapid bone turnover at this stage of life; the tissue lead has been identified isotopically in urine.

Late intramedullary spinal cord metastasis in a patient with lymphoblastic lymphoma: case report.

Late intramedullary spinal cord metastasis of lymphoblastic lymphoma (LBL) is unreported in the literature. The central nervous system (CNS) sites of metastasis previously documented include the spinal leptomeninges causing epidural spinal cord compression or brain praenchymal sites within a year of primary diagnosis. This report represents the first case of intramedullary spinal cord LBL as a late recurrence. The method consists of a case study of one patient with retrospective analysis of tumour tissues from biopsies at ages 5, 9 and 26. The results show that late spinal cord recurrence was microneurosurgically subtotally debulked and later treated with radiotherapy with improvement in neurological deficit. Investigations revealed no evidence of systemic disease and this recurrence appears to be an isolated sanctuary site tumour. A MEDLINE search (1966 - present) of the literature failed to reveal similar reported cases and the authors believe this to be the first late intramedullary spinal cord metastasis in a patient with LBL.

Effect of pH on the thermal denaturation of whey proteins in milk.

The effect of pH on thermal denaturation of four main whey protein fractions in skim milk was examined by gel permeation FPLC. On heating skim milk at 80 degrees C for 0.5-20.0 min over the pH range 5.2-8.8, the extent of denaturation, based on loss of solubility at pH 4.6, increased with heating time and was usually in the order immunoglobulins > serum albumin/lactoferrin > beta-lactoglobulin > alpha-lactalbumin. Rates of denaturation of the immunoglobulins and the serum albumin/lactoferrin fraction were highest at the lower end of this pH range, whereas those of beta-lactoglobulin and alpha-lactalbumin increased over most of the pH range. The effects of pH, addition of Ca, and reduction of disulfide bonds on the rates of the unfolding and aggregation stages of denaturation are discussed.

Impact of diet on lead in blood and urine in female adults and relevance to mobilization of lead from bone stores.

We measured high precision lead isotope ratios and lead concentrations in blood, urine, and environmental samples to assess the significance of diet as a contributing factor to blood and urine lead levels in a cohort of 23 migrant women and 5 Australian-born women. We evaluated possible correlations between levels of dietary lead intake and changes observed in blood and urine lead levels and isotopic composition during pregnancy and postpartum. Mean blood lead concentrations for both groups were approximately 3 microg/dl. The concentration of lead in the diet was 5.8 +/- 3 microg Pb/kg [geometric mean (GM) 5.2] and mean daily dietary intake was 8.5 microg/kg/day (GM 7.4), with a range of 2-39 microg/kg/day. Analysis of 6-day duplicate dietary samples for individual subjects commonly showed major spikes in lead concentration and isotopic composition that were not reflected by associated changes in either blood lead concentration or isotopic composition. Changes in blood lead levels and isotopic composition observed during and after pregnancy could not be solely explained by dietary lead. These data are consistent with earlier conclusions that, in cases where levels of environmental lead exposure and dietary lead intake are low, skeletal contribution is the dominant contributor to blood lead, especially during pregnancy and postpartum.

Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother.

We have obtained stable lead isotope and lead concentration data from a longitudinal study of mobilization of lead from the maternal skeleton during pregnancy and lactation and in which the newly born infants were monitored for 6 months postpartum to evaluate the effects of the local environment on lead body burden of the infant. Samples of maternal and infant blood, urine, and diet and especially breast milk were measured for 21 mothers and 24 infants. Blood lead concentrations were less than 5 microg/dl in all except one subject. The mean lead concentration in breast milk +/- standard deviation was 0.73 +/- 0.70 microg/kg. In seven subjects for whom serial breast milk sampling was possible, the lead concentration varied by factors of from 2 to 4, and for three subjects there was an increase at or after 90 days postpartum. For the first 60-90 days postpartum, the contribution from breast milk to blood lead in the infants varied from 36 to 80%. Multiple linear regression analyses indicated statistically significant relationships for some of the variables of isotope ratios and lead concentrations between breast milk, blood, urine, and diet for infants and mothers. For example, the analyses revealed that both a mother's breast milk 207Pb/206Pb and 206Pb/204Pb ratios and lead concentration provide information to predict her infant's blood 207Pb/206Pb and 206Pb/204Pb ratios. The major sources of lead in breast milk are from the maternal bone and diet. An evaluation of breast milk lead concentrations published over the last 15 years indicates that studies in which the ratio of lead concentrations in breast milk to lead concentrations in whole maternal blood (Multiple>100) were greater than 15 should be viewed with caution because of potential contamination during sampling and/or laboratory analyses. Selected studies also appear to show a linear relationship between breast milk and maternal whole blood, with the percentage of lead in breast milk compared with whole blood of <3% in subjects with blood lead levels ranging from 2 to 34 microgram/dl. The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources.

Dietary lead intakes for mother/child pairs and relevance to pharmacokinetic models.

Blood and environmental samples, including a quarterly 6-day duplicate diet, for nine mother/child pairs from Eastern Europe have been monitored for 12 to >24 months with high precision stable lead isotope analysis to evaluate the changes that occur when the subjects moved from one environment (Eastern Europe) to another with different stable lead isotopes (Australia). The children were between 6 and 11 years of age and the mothers were between 29 and 37 years of age. These data were compared with an Australian control mother/child pair, aged 31 and 6 years, respectively. A rationale for undertaking this study of mother/child pairs was to evaluate if there were differences in the patterns and clearance rates of lead from blood in children compared with their mothers. Blood lead concentrations ranged from 2.1 to 3.9 microg/dl in the children and between 1.8 and 4.5 microg/dl in the mothers, but the mean of differences between each mother and her child did not differ significantly from zero. Duplicate diets contained from 2.4 to 31.8 microg Pb/kg diet; the mean+/- standard deviation was 5.5 +/- 2.1 microg Pb/kg and total daily dietary intakes ranged from 1.6 to 21.3 microg/day. Mean daily dietary intakes relative to body weight showed that the intake for children was approximately double that for the mothers (0.218 vs. 0. 113 microg Pb/kg body weight/day). The correlations between blood lead concentration and mean daily dietary intake either relative to body weight or total dietary intake did not reach statistical significance (p>0.05). Estimation of the lead coming from skeletal (endogenous) sources relative to the contribution from environmental (exogenous) sources ranges from 8 to 70% for the mothers and 12 to 66% for the children. The difference between mothers and children is not statistically significant (p = 0.28). The children do not appear to achieve the Australian lead isotopic profile at a faster rate than their mothers. These data provide evidence that the absorption or uptake of lead from dietary sources is similar in adult females and children of the age in this study. In spite of lower bone lead and faster bone remodeling and recycling in children compared with adult females, we see no differences between the mothers and their children in overall contribution of tissue lead to blood lead. Results from this study suggest that fractional absorption of ingested lead by children 6-11 years of age is comparable with absorption patterns observed among adult females in the 29-37-year-old age range. Because pharmacokinetic models apply a 40-50% absorption even for 7-year-old children, further investigations on fractional absorption of ingested lead by young children are warranted. Further investigations are especially needed in younger children than those who were subjects in the current study, particularly children in the 1-3-year-old age range. In addition, the effect of nutritional status and patterns of food intake on children's lead absorption require investigation, particularly given the increased prevalence of marginal nutritional status among low-income populations that are at increased risk of elevated blood lead levels.

Changes in casein composition of goats' milk during the course of lactation: physiological inferences and technological implications.

Five British Saanen goats were milk sampled during the first 39 weeks of lactation to determine changes in casein composition. Caseins were separated by anion- and cation-exchange FPLC to determine the relative amounts of the individual caseins. Acid, alkaline and SDS-PAGE were used to determine possible genetic polymorphisms and observe any lactational changes. Total casein nitrogen was determined using a micro-Kjeldahl method and this allowed the concentrations of individual caseins to be calculated. The milk of one animal, which had the deduced genotype alpha s1-CnAB, showed higher concentrations of both total and alpha s1-casein. The remainder of the group were either heterozygous alpha s1-CnBE or, more probably, homozygous alpha s1-CnE and produced milk of a generally lower protein concentration. Both FPLC and PAGE results showed that the relative amounts and concentrations of alpha s2-casein decreased with stage of lactation, consistent with its susceptibility to proteolysis. The relative amounts of the breakdown products of plasmin attack on beta-casein, gamma-caseins, were highly negatively correlated with milk yield (r = -0.942, P < 0.001) in the declining phase of lactation, reflecting the gradual involution of the gland at this time. The relative amount of kappa-casein increased by approximately 50% after peak lactation and its concentration almost doubled near the end of lactation. These compositional changes may alter the processing qualities of goats' milk in relation to cheese production.

Lead bioavailability in the environment of children: blood lead levels in children can be elevated in a mining community.

Lower blood lead averages in mining communities, compared with other child exposure settings, e.g., innercity areas of the United States and smelter communities, have been attributed to lower bioavailability of lead to children in the mining areas. Direct supporting evidence of the lower bioavailability has, however, generally been lacking. Elevated blood lead levels for approximately 85% of children with > 10 micrograms/dl have been reported from the Broken Hill mining community in Australia. Lead isotope, optical, and scanning electron microscope analyses on the lead species from soils and dusts show them to be derived mainly from weathered ore body material. Solubility tests using 0.1M HCl on the -53 + 38 microns fraction of soil and dust show the lead species to have a high degree of bioavailability. Ingestion of soil and dust, either directly or via mouthing activity, is the main source and pathway for elevated blood lead in children from this community.

Milk composition and lactation of beta-casein-deficient mice.

beta-Casein is a major protein component of milk and, in conjunction with the other caseins, it is assembled into micelles. The casein micelles determine many of the physical characteristics of milk, which are important for stability during storage and for milk-processing properties. There is evidence that suggests that beta-casein may also possess other, nonnutritional functions. To address the function of beta-casein, the mouse beta-casein gene was disrupted by gene targeting in embryonic stem cells. Homozygous beta-casein mutant mice are viable and fertile; females can lactate and successfully rear young. beta-Casein was expressed at a reduced level in heterozygotes and was completely absent from the milk of homozygous mutant mice. Despite the deficiency of beta-casein, casein micelles were assembled in heterozygous and homozygous mutants, albeit with reduced diameters. The absence of beta-casein expression was reflected in a reduced total protein concentration in milk, although this was partially compensated for by an increased concentration of other proteins. The growth of pups feeding on the milk of homozygous mutants was reduced relative to those feeding on the milk of wild-type mice. Various genetic manipulations of caseins have been proposed for the qualitative improvement of cow's milk composition. The results presented here demonstrate that beta-casein has no essential function and that the casein micelle is remarkably tolerant of changes in composition.