No linkage or association between multiple sclerosis and the myelin basic protein gene in affected sibling pairs.

Myelin basic protein was examined as a candidate gene for susceptibility to multiple sclerosis using two adjacent amplification fragment length polymorphisms (AmpFLPs), containing seven and six highly informative alleles respectively. No allelic association was found with multiple sclerosis, comparing 77 cases and 88 controls, and there was no evidence for linkage in 73 affected sibling pairs, using the methods of identity by descent and identity by state.     

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.     

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis.

T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential.     

Frontal lobe activation during object alternation acquisition

Object alternation (OA) tasks are increasingly used as probes of ventral prefrontal functioning in humans. In the most common variant of the OA task, subjects must deduce the task rule through trial-and-error learning. To examine the neural correlates of OA acquisition, the authors measured regional cerebral blood flow with positron emission tomography while subjects acquired an OA task, performed a sensorimotor control condition, or performed already learned and practiced OA. As expected, activations emerged in the ventral prefrontal cortex. However, activation of the presupplemental motor area was more closely associated with successful task performance. The authors suggest that areas beyond the ventral prefrontal cortex are critically involved in OA acquisition.     

February 2003: a 53-year-old male with new onset seizures

The February COM. A 53-year-old obese man presented with new onset seizures and an MRI scan revealed a large cystic and necrotic heterogeneously enhancing left frontal mass. Craniotomy revealed a firm subdural tumor on the cortical surface that was delivered en-bloc preserving the pial planes and stripping it from the falx cerebri. The tumor consisted of multiple irregular fragments of white-tan rubbery tissue admixed with globules of bosselated, white-tan rubbery tissue and a fragment of bone. Sections of the tumor revealed mature hyaline cartilage with no atypia of the chondrocytes. There was focal mineralization and endochondral ossification. A diagnosis of intracranial mesenchymal osteochondroma was made. Osteochondroma, a benign cartilaginous neoplasm comprised of mature hyaline cartilage with focal ossification, is the most common benign bone tumor. Extraskeletal (mesenchymal) osteochondromas are known to originate from non-skeletal or non-cartilaginous tissue. Intracranial osteochondromas are uncommon, typically arising from the base of the skull. Only about 15% of intracranial osteochondromas arise supratentorially, from the dura, usually in a parafalcine frontoparietal location and some have been a component of Maffucci's syndrome and Ollier disease. Intracranial osteochondromas can occur at any age with a predilection for younger individuals. Intracranial mesenchymal osteochondromas exhibit a benign clinical course. Typically, the histomorphology resembles mature hyaline cartilage without anaplastic proliferation of chondrocytes or nuclear atypia, with a lobular arrangement of clusters of lacunae containing single chondrocytes. Transition to osteochondrosarcoma has rarely been documented.     

Cost-effective analysis of candidate genes using htSNPs: a staged approach

We have previously shown that the selection of haplotype tag single nucleotide polymorphisms (htSNPs) and their statistical analysis in a multi-locus transmission/disequilibrium test (TDT) results in a more cost-effective genotyping strategy in disease association studies of genes by minimising redundancy due to linkage disequilibrium between SNPs. Further savings can be achieved by the use of a two-stage genotyping strategy. This approach is illustrated here in conjunction with the multi-locus TDT in determining whether common alleles of the immune regulatory genes RANK and its ligand TRANCE (RANKL) are associated with type 1 diabetes (T1D). A saving of approximately 75% of potential genotyping reactions could be made with minimal loss of power. There was little evidence from our analysis for association between the TRANCE and RANK genes and T1D in the populations tested.     

Mortality of patients with mood disorders: follow-up over 34-38 years

BACKGROUND: All follow-up studies of causes of death in affective disordered patients have found they have markedly elevated suicide rates and a less reproducible increased mortality from other causes. The reported rates by gender, disorder type and treatment are more variable. METHODS: Hospitalised affective disordered patients (n=406) were followed prospectively for 22 years or more. Later, mortality was assessed for 99% of them at which time 76% had died. RESULTS: Standardised Mortality Rates (observed deaths/expected deaths) for patients were elevated especially for suicide and circulatory disorders in both men and women. Women actually had higher suicide rates but that did not take into account the twofold increase in general population rates for men. Unipolar patients had significantly higher rates of suicide than bipolar Is or IIs. In all groups long term medication treatment with antidepressants alone or with a neuroleptic, or with lithium in combination with antidepressants and/or neuroleptics significantly lowered suicide rates even though the treated were more severely ill. Although at the age of onset the suicide rates were most elevated, from ages 30 to 70 the rates were remarkably constant despite the different courses of illness. LIMITATIONS: The patients were identified as inpatients and followed prospectively. The treatments were uncontrolled and are not quantifiable but were documented during the follow-up. CONCLUSIONS: Men and women hospitalised for affective disorders have elevated mortality rates from suicide and circulatory disorders. Unipolars have higher suicide rates than bipolar Is or IIs. Long term medication treatment lowers the suicide rates, despite the fact that it was the more severely ill who were treated.