Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study

Serum thyroid autoantibodies to thyroglobulin (TG) and thyroid microsomes (M) were measured by ELISA prospectively in 37 manic depressive patients prior to receiving lithium carbonate and during therapy with this drug for a mean of 16.2 months. They were also measured once in 27 normal subjects and several times in five psychiatric patients not receiving lithium. Sixteen patients (43%) had either thyroglobulin, microsomal antibodies or both before receiving lithium therapy. During therapy significant fluctuations in antibody titre, both upwards and downwards were observed in ten out of 12 patients with M antibodies and in nine out of 11 with TG antibodies. The fluctuations in antibody titre are consistent with an immunomodulatory effect of lithium as has been shown in animal studies. It is suggested that psychiatric patients should have thyroid antibodies measured routinely before and during lithium therapy.     

Disseminated toxoplasmosis in cardiac transplantation.

The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients. Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation. Eleven of 30 (37%) of donors had Toxoplasma antibody. The were four occasions when a negative recipient received a heart from a positive donor. Three survived the immediate postoperative period and two became infected with toxoplasmosis. The implications of this are discussed. Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient. Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.     

Depletion of neuropeptides during wound healing in rat skin

The peptides substance P, calcitonin gene-related peptide and somatostatin are present in nerve fibres in mammalian, including human, skin. There is evidence that in addition to having a putative neurotransmitter role, they may be trophic agents: a study was therefore undertaken of peptide changes during wound healing in rat skin. A significant depletion of the neuropeptides was found in the region of the wound within two days, and this persisted for two weeks. A smaller and delayed depletion also occurred in intact skin of the same dermatome, but not in an adjacent dermatome.     

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

Stress, coping, and hepatitis B antibody status

OBJECTIVE: The present study investigated the association between exposure to stressful life events, coping style, and antibody status after hepatitis B vaccination. METHODS: Two hundred sixty medical school undergraduates, who had received the three-dose hepatitis B vaccine before recruitment to this study, completed questionnaires measuring exposure to stressful life events during the past year, customary coping strategies, and health behaviors. Antibodies against hepatitis B surface antigen were determined; levels <100 mIU/ml were deemed inadequate. RESULTS: Two participant cohorts were identified: those vaccinated within the last year and those vaccinated earlier. In the early vaccination cohort, participants with greater-than-average stress exposures had a more than two-fold increased risk of having an inadequate antibody titer. Coping by accepting the reality of stressful situations proved protective, whereas coping by substance use increased the risk of having an inadequate antibody count in this cohort. These associations remained significant after adjustment for possible mediators. Furthermore, the effects of stress and coping were largely independent of one another. Neither stress nor coping was significantly associated with antibody status in the recently vaccinated cohort. CONCLUSIONS: The present study confirms that the immune system is sensitive to variations in psychological factors. Stressful life events and coping strategy seem to have a continuing impact on hepatitis B antibody status.     

Genomic instability occurs in colorectal carcinomas but not in adenomas

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER⁺). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER⁺, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc.     

CSnrc: correlated sampling Monte Carlo calculations using EGSnrc

CSnrc, a new user-code for the EGSnrc Monte Carlo system is described. This user-code improves the efficiency when calculating ratios of doses from similar geometries. It uses a correlated sampling variance reduction technique. CSnrc is developed from an existing EGSnrc user-code CAVRZnrc and improves upon the correlated sampling algorithm used in an earlier version of the code written for the EGS4 Monte Carlo system. Improvements over the EGS4 version of the algorithm avoid repetition of sections of particle tracks. The new code includes a rectangular phantom geometry not available in other EGSnrc cylindrical codes. Comparison to CAVRZnrc shows gains in efficiency of up to a factor of 64 for a variety of test geometries when computing the ratio of doses to the cavity for two geometries. CSnrc is well suited to in-phantom calculations and is used to calculate the central electrode correction factor Pcel in high-energy photon and electron beams. Current dosimetry protocols base the value of Pcel on earlier Monte Carlo calculations. The current CSnrc calculations achieve 0.02% statistical uncertainties on Pcel, much lower than those previously published. The current values of Pcel compare well with the values used in dosimetry protocols for photon beams. For electrons beams, CSnrc calculations are reported at the reference depth used in recent protocols and show up to a 0.2% correction for a graphite electrode, a correction currently ignored by dosimetry protocols. The calculations show that for a 1 mm diameter aluminum central electrode, the correction factor differs somewhat from the values used in both the IAEA TRS-398 code of practice and the AAPM's TG-51 protocol.