Pathogenesis and pathology of scrapie after stereotactic injection of strain 22L in intact and bisected cerebella

The mechanisms involved in the spread of scrapie within the brain remain unclear. To examine this issue the 22L scrapie strain was injected in one side of the cerebellum of mice in which the cerebellum had been bisected prior to injection. Another group of animals received the same injection into intact cerebella, i.e. without prior bisection. We found that bisection of the cerebella delayed the spread of scrapie agent from the injection site to the contralateral side of the cerebellum and that the occurrence of vacuolization was not as extensive and was markedly delayed in the uninjected side compared to its occurrence after injection in the intact cerebellum. Replication of agent in an area preceded the development of vacuolization in that area by several weeks. There was marked loss of Purkinje cells on the injected side of bisected cerebella, with no loss seen on the uninjected side. The incubation period of scrapie disease in mice injected after cerebellar bisection was significantly longer than after the injection of intact cerebella. The results in this study suggest that the scrapie agent spreads along intact nerve cell tracts, probably by axonal transport.     

A clue from a self-report questionnaire to distinguish rheumatoid arthritis from noninflammatory diffuse musculoskeletal pain. The P-VAS:D-ADL ratio

A clue to distinguishing rheumatoid arthritis (RA) from noninflammatory diffuse musculoskeletal pain is described on the basis of 2 self-report questionnaire scales, one to assess difficulty in activities of daily living (D-ADL) and a pain visual analog scale (P-VAS). Patients with RA have significantly higher scores on the D-ADL scale compared with the P-VAS scale, while patients with noninflammatory diffuse musculoskeletal pain show the reciprocal pattern. Therefore, the ratio of the P-VAS:D-ADL scores differed significantly in the 2 groups. Ratios of less than 3 were seen in 67% of RA patients versus 28% of patients with noninflammatory diffuse musculoskeletal pain, while ratios greater than 5 were seen in 27% of patients with noninflammatory diffuse musculoskeletal pain, but not in any patients with RA. This simple ratio is clearly not a diagnostic test, but provides an initial approach to diagnosis in rheumatic diseases using a self-report questionnaire.     

Old age and new policy

In light of the projection of increasing deficits in the present Medicare program, we must rethink our goals for health in old age and curb our insatiable appetite for longer life regardless of expense. The failure of efforts to control costs through efficiency measures has forced elderly persons to forgo decent long-term or home care, and yet public opinion continues to expect more and better health care with no corresponding inclination to pay for it. The emphasis of entitlement programs must be shifted from short-term, critical care medicine for the elderly to the provision of care that improves the quality of their day-to-day life, while not necessarily extending that life; the most expensive forms of life-extending care would then be rationed according to a flat age limitation decided upon collectively by society.     

Production and characterization of high titer antibodies to galactocerebroside

High titer antibodies primarily of the IgG class were produced against galactocerebroside (GalC) by including keyhole limpet hemocyanin (KLH) and supplemental M. tuberculosis in the adjuvant mixture used for immunization of rabbits. Antibody titers were determined by an ELISA in which microtiter wells were coated with liposomes containing lecithin, cholesterol and GalC. The antibodies showed reactivity with GalC and psychosine, but not glucocerebroside, sulfatide, mixed gangliosides or asialo GM1. Specificity was further demonstrated by absorption of antibodies with GalC. Binding was inhibited by galactose, but only at high concentrations. Further, the antibodies did not bind to any brain proteins on immunoblots, indicating lack of reactivity with glycoproteins which might contain a terminal galactose. Antibodies to GalC are directed against different determinants than those reacting with peanut agglutinin since the lectin will not react with GalC, and the antibodies will not react with asialo GM1. The antibodies raised to GalC by this method show specific staining for oligodendroglia in culture. Peanut agglutinin binds intensely to process-bearing GalC+ oligodendroglia, but very poorly to the membrane sheets elaborated by oligodendroglia after longer times in culture. Other process-bearing GalC-, GFAP- cells were also stained with peanut agglutinin; these cells may represent glial precursors.     

Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline

In order to further evaluate the extent to which particular 5-HT receptor subtypes (5-HT1, 5-HT2) might be involved in the behavioral effects of hallucinogenic drugs, rats were trained to discriminate mescaline (10 mg/kg i.p.) from saline and were given substitution (generalization) and combination (antagonism) tests with putatively selective serotonergic and related neuroactive compounds. The mescaline cue generalized to relatively high doses of the 5-HT2 agonists, 2,5-dimethoxy-4-methylamphetamine (DOM), LSD and psilocybin; the extent of generalization to 5-HT1 agonists (8-hydroxy-2-[diethylamino]tetralin (8-OHDPAT), RU-24969 and 8-hydroxy-2-[di-n-propylamino]tetralin (TFMPP] was unclear. Combinations of the training drug and sufficiently high doses of 5-HT2 antagonists (ketanserin, LY-53857, pirenperone) were followed by saline-lever responding; less selective central 5-HT (metergoline), and DA (SCH-23390, haloperidol) antagonists, did not block the mescaline cue. These data suggest that 5-HT2 receptors are involved in the stimulus properties of mescaline.     

Percentage Change in Antenatal Body Mass Index as a Predictor of Neonatal Macrosomia

PURPOSE We wanted to evaluate the predictive value of percentage change in antenatal maternal body mass index (BMI) as it relates to macrosomia, as well as to compare change in pregnancy BMI with existing weight gain guidelines.     

Chondromalacia patellae: assessment with MR imaging

Magnetic resonance (MR) images of the posterior patellar hyaline articular cartilage were obtained in 23 subjects to determine if MR imaging could accurately demonstrate the patellar cartilage. Arthroscopy was used as the standard of reference. Three subjects were asymptomatic volunteers. In the remaining 20 who had patellofemoral pain, arthroscopy was performed before MR imaging in seven and afterward in 12; one did not undergo arthroscopy. MR imaging showed focal areas of swelling of the patellar cartilage, focal hypointensity, surface irregularity, areas of thinning, and areas of cartilage loss with exposure of subchondral bone. The surgical findings agreed with those from MR images in all seven patients who underwent arthroscopy before MR imaging and in ten of the 12 who underwent surgery afterward. MR imaging is an accurate means of examining the posterior patellar cartilage and should be considered as an alternative to diagnostic arthroscopy when chondromalacia patellae is suspected.