Cardiac effects of lead in drinking water of rats.

1. There is no known cause for the increased mortality due to ischaemic heart disease in soft water areas. Since the lead concentration of soft water is elevated in houses with lead plumbing, studies have been carried out to determine the effects of lead on the heart of rats. 2. Rats were given drinking water containing lead for 1 year at concentrations similar to those found previously in Glasgow, which has a soft water supply. 3. There was increasing deposition of lead in the heart and a fall in the cardiac levels of the enzymes ferrochelatase and delta-aminolaevulinic acid dehydratase. These changes are maximal after 6 months, when there were marked electron-microscopic changes in the myocardium and myocardial mitochondria. 4. Further studies are needed to determine whether lead is a cause of the increased mortality from ischaemic heart disease in soft water areas.     

The effect of steering on the physiological energy cost of wheelchair propulsion

Previous studies of the energy cost of wheelchair propulsion have used ergometers or tracks requiring little steering. We have measured minute ventilation (VE), oxygen consumption (VO2), carbon dioxide output (VCO2) and heart rate (HR) during exercise in a two arm, hand-rim propulsion wheelchair on a treadmill, and on three tracks of increasing tortuosity in eight able-bodied subjects. During propulsion at 0.6 m/sec, VE, VO2, and VCO2 were significantly greater on the track with the maximal steering component than on that with the minimal steering component, or on the treadmill with no steering component. Heart rate was significantly higher on the maximal compared to minimal steering component track. Exercise at speeds varying from 0.2 to 1.0 m/sec showed that VO2 and VCO2 were significantly higher on the medium steering component track than on the treadmill at speeds of 0.6 m/sec and above. We conclude that the effort of steering contributes significantly to the energy cost of wheelchair propulsion particularly at higher speeds.     

Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of the fasting plasma triglyceride concentration to insulin secretion.

Plasma lipoprotein concentrations in 64 untreated adult onset diabetics were compared to the lipoprotein levels found in non diabetics. No significant difference was found. The relationship of the fasting plasma triglyceride concentration to the plasma immunoreaction insulin response to 50 g glucose orally was investigated. Using correlation analysis a significant and insulin response in the non diabetics but not in the diabetics.     

P21Therapeutic Efficacy of Plasmapheresis for the Treatment of Refractory Pruritis of Primary Billiary Cirrhosis: 2 Case Reports.

Primary billiary cirrhosis (PBC), a chronic cholestatic disease of presumed autoimmune aetiology, is characterised by progressive intrahepatic bile duct destruction, liver cirrhosis, failure, and death, unless treated by liver transplantation. Distressing pruritis (skin itch), fatigue and metabolic bone diseases frequently complicate this disease, significantly reducing quality of life. The pathogenesis of pruritis remains uncertain. Some unknown pruritogen(s) produced by the liver have been implicated which accumulate in the plasma as a result of chronic cholestasis. Recent evidence also suggests a central mechanism, with increased neurotransmission/neuromodulation mediated by endogenous opioid agonists. Therapeutic interventions include unabsorbable oral resins, urso-deoxycholeic acid, opiate antagonists and rifampicin. More experimental therapies include: partial diversion of bile; charcoal haemoperfusion; UVA; plasmapheresis and albumin-based dialysis (for patients with renal impairment). We used plasma exchange for the treatment of intractable pruritis in two patients with primary billiary cirrhosis. Both were females between ages of 50–60 years, refractory to all medical treatments and severely disabled by intractable pruritis and fatigue. In the first patient, weekly to fortnightly plasmapheresis considerably reduced the intensity of itch and stabilized her condition until her liver transplant. The second patient was treated for a relapse of PBC following her liver transplant. She significantly improved with more than 50% reduction in the intensity of her generalized itch with healing of excoriations, and was able to sleep for 4 h undisturbed after only one procedure. We suggest that plasmapheresis may be helpful for the pruritis of chronic cholestasis refractory to medical management. It could also be considered for the initial treatment of selected patients in combination with other therapies.     

Effect of Variation in Diacylglycerol Kinase Eta (DGKH) Gene on Brain Function in a Cohort at Familial Risk of Bipolar Disorder

Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH''s risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high-risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype.     

A novel mutation in ferroportin implicated in iron overload

BACKGROUND/AIMS: Hereditary iron overload is associated with mutations in a number of genes involved in the regulation of iron metabolism. In this study we examined the molecular basis of iron overload in an individual from New Zealand and characterised the molecular and cellular defect. METHODS: We analysed the ferroportin gene and a control population was screened using allele-specific PCR and denaturation analysis. Molecular characterisation was performed by immunofluorescence microscopy analysis of transfected cells. We analysed the ferritin levels of cells expressing wild-type and mutant ferroportin to define the nature of the molecular defect on iron transport. RESULTS: We identified a novel nucleotide substitution (c. 1014T>G) in the ferroportin gene leading to the S338R mutation. This mutation is not a common polymorphism. Cellular analysis of the mutant protein indicates that this amino acid change does not affect the localisation of the protein or its ability to transport iron. CONCLUSIONS: The S338R mutation results in a mutated ferroportin associated with iron overload and is predicted insensitive to regulation by the iron regulatory hormone hepcidin.     

Prefrontal function and activation in bipolar disorder and schizophrenia

OBJECTIVE: Distinctive patterns of speech and language abnormalities are associated with bipolar disorder and schizophrenia. It is, however, unclear whether the associated patterns of neural activation are diagnosis specific. The authors sought to determine whether there are differences in language-associated prefrontal activation that discriminate bipolar disorder and schizophrenia. METHOD: Forty-two outpatients with bipolar I disorder, 27 outpatients with schizophrenia, and 37 healthy comparison subjects were recruited. Differences in blood oxygen level-dependent activity were evaluated using the Hayling Sentence Completion Test and analyzed in Statistical Parametric Mapping (SPM) 2. Differences in activation were estimated from a sentence completion versus rest contrast and from a contrast of decreasing sentence constraint. Regional activations were related to clinical variables and performance on a set shifting task and evaluated for their ability to differentiate among the three groups. RESULTS: Patients with bipolar disorder showed differences in insula and dorsal prefrontal cortex activation, which differentiated them from patients with schizophrenia. Patients with bipolar disorder recruited the orbitofrontal cortex and ventral striatum to a greater extent relative to healthy comparison subjects on the parametric contrast of increasing difficulty. The gradient of ventral striatal and prefrontal activation was significantly associated with reversal errors in bipolar disorder patients. CONCLUSIONS: Brain activations during the Hayling task differentiated patients with bipolar disorder from comparison subjects and patients with schizophrenia. Patients with bipolar disorder showed abnormalities in frontostriatal systems associated with performance on a set shifting task. This finding suggests that bipolar disorder patients engaged emotional brain areas more than comparison subjects while performing the Hayling task.