Postmortem findings in a case of variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulfate.

BACKGROUND: A small number of patients with variant Creutzfeldt-Jakob disease (vCJD) have been treated with intraventicular pentosan polysulfate (iPPS) and extended survival has been reported in some cases. To date, there have been no reports on the findings of postmortem examination of the brain in treated patients and the reasons for the extended survival are uncertain. We report on the neuropathological findings in a case of vCJD treated with PPS. METHODS: Data on survival in vCJD is available from information held at the National CJD Research and Surveillance Unit and includes the duration of illness in 176 cases of vCJD, five of which were treated with iPPS. One of these individuals, who received iPPS for 8 years and lived for 105 months, underwent postmortem examination, including neuropathological examination of the brain. RESULTS: The mean survival in vCJD is 17 months, with 40 months the maximum survival in patients not treated with PPS. In the 5 patients treated with PPS survival was 16 months, 45 months, 84 months, 105 months and 114 months. The patient who survived 105 months underwent postmortem examination which confirmed the diagnosis of vCJD and showed severe, but typical, changes, including neuronal loss, astrocytic gliosis and extensive prion protein (PrP) deposition in the brain. The patient was also given PPS for a short period by peripheral infusion and there was limited PrP immunostaining in lymphoreticular tissues such as spleen and appendix. CONCLUSIONS: Treatment with iPPS did not reduce the overall neuropathological changes in the brain. The reduced peripheral immunostaining for PrP may reflect atrophy of these tissues in relation to chronic illness rather than a treatment effect. The reason for the long survival in patients treated with iPPS is unclear, but a treatment effect on the disease process cannot be excluded.

HIV vaccine acceptability and culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada.

This study explored HIV vaccine acceptability and strategies for culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada, among those at highest HIV risk. We conducted four focus groups (n=23) with Aboriginal male (1) and female (1) service users, peer educators (1) and service providers (1) in Ontario, Canada. Transcripts were analysed with narrative thematic techniques from grounded theory, using NVivo. Participants' mean age was 37 years; about half (52%) were female, half (48%) Two-spirit or lesbian, gay or bisexual (LGB)-identified, 48% had a high-school education or less and 57% were unemployed. Vaccine uptake was motivated by community survival; however, negative HIV vaccine perceptions, historically based mistrust of government and healthcare institutions, perceived conflict between western and traditional medicine, sexual prejudice and AIDS stigma within and outside of Aboriginal communities, and vaccine cost may present formidable obstacles to HIV vaccine acceptability. Culturally appropriate processes of engagement emerged on individual levels (i.e., respect for self-determination, explanations in Native languages, use of modelling and traditional healing concepts) and community levels (i.e., leadership by Aboriginal HIV advocates and political representatives, identification of gatekeepers, and procuring Elders' endorsements). Building on cultural strengths and acknowledging the history and context of mistrust and social exclusion are fundamental to effective HIV vaccine dissemination.

Are triglyceride breast implants really biocompatible?

A case of augmentation mammaplasty with triglyceride implants is presented. Histological examination of the capsules 3 years postimplantation showed retained, irregular, refractile yellow-brown fragments embedded in granulomatous tissue.

Can reduced folic acid and vitamin B12 levels cause deficient DNA methylation producing mutations which initiate atherosclerosis?

Atherosclerosis of the vascular system has classically been attributed to elevated serum cholesterol concentrations. Recently, it has been found that reduced serum levels of folic acid, vitamin B12, and vitamin B6 are related to the etiology of atherosclerosis and coronary heart disease. These deficiencies lead to inadequate production of S-adenosyl-methionine, creating a condition of hypomethylation. It is hypothesized that this causes hypomethylation of the DNA in cells in the arterial intima resulting in mutation and proliferation of smooth-muscle cells which lead to the formation of atheroma. It is further hypothesized that such action can be reversed by supraphysiological doses of these three vitamins to reduce or remove existing atheroma. It is recommended that all patients suffering from atherosclerosis and having deficiencies of any of these three vitamins and/or an elevation of serum homocysteine receive supplementation to prevent worsening of their condition.

Hypothermia in multiple sclerosis.

Five patients with clinically definite multiple sclerosis are reported who presented with acute relapses associated with hypothermia. Repeated episodes of hypothermia were seen in four. Thrombocytopenia was associated with the hypothermia in four patients. Further investigation disclosed a tendency to chronic hypothermia and suggested an altered thermoregulatory set point in one patient, when MRI, endocrine, and autonomic studies failed to localise a lesion in the hypothalamus, but subsequent necropsy showed hypothalamic lesions. In such patients a predisposition to altered thermoregulation may occur due to direct involvement of the hypothalamus or from combined lesions affecting hypothalamic outflow to the brainstem and spinal cord.

Molecular recognition in the minor groove of the DNA helix. Studies on the synthesis of oligonucleotides and polynucleotides containing 3-deaza-2'-deoxyadenosine. Interaction of the oligonucleotides with the restriction endonuclease EcoRV.

An improved procedure for the preparation of 3-deaza-2'-deoxyadenosine (d3CA) is described which is suitable for the synthesis of gram quantities of this analogue. Using phosphoramidite chemistry d3CA has been incorporated into the Eco RV restiction endonuclease recognition sequence (underlined) present in the self-complementary dodecamer d(GACGATATCGTC). The modified oligonucleotides have been thoroughly characterised by nucleoside composition analysis, circular dichroism and thermal melting studies. Studies with Eco RV show that incorporation of d3CA into either the central or outer dA-dT base-pair results in a substantial reduction in the rate of cleavage. The two-step conversion of d3CA to 3-deaza-2'-deoxyadenosine-5'-O-triphosphate (d3CATP) via the 5'-O-tosylate is also described. d3CATP is not a substrate in the poly[d(AT)].poly[d(AT)] primed polymerisation for either E. coli DNA polymerase I or Micrococcus luteus DNA polymerase. In a more detailed kinetic analysis d3CATP was shown to be a competitive inhibitor of E. coli DNA polymerase I with respect to dATP.

Sunscreens and PUVA.

Sunscreening creams have been tested for their capacity to protect non-lesional skin in patients receiving 8-methoxypsoralen photochemotherapy (PUVA). Cosmetically acceptable preparations such as Contralum Ultra and RoC Total are effective UVA sunscreens which may reduce the risk of carcinogenesis. A simple test of efficacy is described.

Magnetic field therapy-does it affect soft tissue? *.

Claims that magnetic field therapy improves peripheral circulation and tissue oxygenation have been tested on normal volunteers. Transcutaneous oxygen tension measurements were made and skin temperatures measured in a double blind trial. Using recommended magnetic field configurations, no significant effects attributable to the magnetic field therapy could be demonstrated. J Orthop Sports Phy Ther 1983;4(4):241-246.