Ultrastructural changes in the frontal cortex and hippocampus in the ageing marmoset

The ultrastructure of the cells and capillaries of the frontal cortex and hippocampus was studied in marmosets to assess age-related changes. The appearances in the brains of four marmosets, more than 12 years of age, were compared with those of two young marmosets aged 26 and 21 months. There was widespread accumulation of lipofuscin in neurons, glial cells, perivascular macrophages and pericytes, but not in endothelial cells. Many of the nerve cell nuclei showed marked membrane infolding, alteration of nuclear morphology and occasional inclusions. A few degenerated and dystrophic axons containing abnormal organelles were seen. The capillaries displayed irregularly thickened and split basal laminae. No neurofibrillary tangles, neuritic plaques, amyloid deposits or granulovacuoles were present. These changes are compared to those occurring in other animal species and in man during ageing.     

National Alliance for Oral Health Consensus Conference on Medically Necessary Oral Health Care: Legal issues

This paper examines medical malpractice law as it applies to medically necessary oral health care. The basic legal concepts and reported cases involving medically necessary oral health care are reviewed. It is concluded that dental professionals and consumer advocates must advance their educational and legislative advocacy efforts so that health professional colleagues and the public will become aware of the importance of these services and insurers will routinely include coverage of medically necessary oral health care in their medical and dental policies. While failure to provide medically necessary oral health care can be violative of patient rights and legally actionable, medical malpractice litigation should always be the behavior modifier of last resort.     

Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.     

A technique for eliminating allele specific amplification failure during DNA amplification of heterozygous cells for preimplantation diagnosis

Advances in techniques of molecular biology have made possible the amplification of specific genes from single cells. This has a major clinical application in preimplantation diagnosis of monogenic disorders. However, the incidence of allele specific amplification failure (allele drop out) in heterozygous single cells can lead to misdiagnosis and the transfer of affected embryos. Few studies have been done to investigate the actual cause of allele drop out, although some investigators have succeeded in reducing but not eliminating it. Here we report the efficiency of amplifying both alleles in heterozygous cells lysed according to two different protocols. A total of 177 heterozygous cells from carriers of cystic fibrosis (CF) and haemoglobin C (HbC) were lysed using two different lysis buffers. Interestingly none of the cells that were lysed with sodium dodecyl sulphate/proteinase K showed any example of allele specific amplification failure whereas in those lysed by KOH/dithiothreitol it was present in 17.6 and 4.7% of the CF and HbC cells respectively. Our results suggest that the phenomenon of allele specific amplification failure is at least in part dependent on the lysis buffer used.      

Epidemiology and ethics in the neonatal intensive care unit

There are many ethical dilemmas in the neonatal intensive care unit (NICU), and almost as many solutions as dilemmas. Religion, philosophy, natural law, civil law, criminal law, to name but a few, have each been invoked as a source of authority to resolve the inevitable conflicts arising at the confluence of uncertain outcome, physical pain, and financial expenditure. This article takes a different approach. Here we begin by envisioning what we would most like to know about NICU care that we do not currently know (or at least is not widely known), and then combine "thought experiments" with preliminary "real experiments" to acquire a hypothetical database from which ethics in the NICU can be informed.     

beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease

Impaired olfaction, hyposmia or anosmia are part of the clinical phenotype in neurodegenerative disorders including Alzheimer's disease (AD). It has been proposed that the most severely affected areas are interconnected with the central olfactory system in contrast to the relative sparing of other sensory areas which lack olfactory connections. The pathology of the first synaptic relay in the olfactory pathway, the olfactory bulb (OB), has been studied in AD, but the results have been inconsistent. In order to define more fully the pathology of the OB, we analysed 15 AD and 15 control cases, using amyloid and tau immunohistochemistry on serial sections. This study demonstrates for the first time that all layers of the OB are severely affected in AD and in normal ageing. The principal effector cells of the OB, the mitral cells, developed neurofibrillary tangles (NFTs) both in AD and in controls. All the cases, with the exception of two of the controls, contained NFTs. Amyloid immunoreactivity was detected in diffuse, primitive, classical and compact deposits in AD, while five control cases contained mainly diffuse deposits. We did not find a correlation between amyloid deposition and NFT formation. Among the control cases, two contained neither amyloid nor NFTs, eight had NFTs but no amyloid and only five had both NFTs and amyloid. All the AD cases had NFT and amyloid deposition. Our data suggest that the earlier pathology in the OB is NFT formation and more than ten NFTs/section is compatible with 93.3% diagnostic accuracy for AD.