Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease.

Our earlier studies using the Consortium to Establish a Registry of Alzheimer's Disease neuropsychological battery showed that delayed recall was a highly sensitive indicator of early Alzheimer's disease. None of the learning and memory measures in the battery were found to be useful in staging the severity of this form of dementia. This study explores the nonmemory functions (fluency, naming, and praxis) of the Consortium to Establish a Registry of Alzheimer's Disease battery and asks whether performance on any of these measures adds to the detection of early Alzheimer's disease or is sensitive to the later progression of the illness. We stratified patients with this disease according to severity (mild, moderate, severe), and compared them with age-, education-, and gender-matched control subjects (group N = 49 each). Multivariate procedures and cutting scores were used to determine the efficacy of the various measures in distinguishing between the cases and control subjects. Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease. Confrontation naming was the only nonmemory factor that assisted in this discrimination. For staging the illness, a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease. Measures of delayed recall quickly "bottomed out" in the patients with Alzheimer's disease and proved of little value in staging the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new case of congenital dyserythropoietic anaemia, type III: studies of the cell cycle distribution and ultrastructure of erythroblasts and of nucleic acid synthesis in marrow cells.

The clinical and laboratory findings in an asymptomatic 19-year-old Welshman with congenital dyserythropoietic anaemia (CDA) type III are described. The blood film showed macrocytosis and red cell fragmentation and there was biochemical evidence of intravascular haemolysis. The bone marrow showed erythroid hyperplasia, megaloblastic erythropoiesis and several giant multinucleate erythroblasts. Some mononucleate erythroblasts were large and had relative DNA contents of 4-8c and the bi- and multinucleate erythroblasts had total DNA contents of 2-16c. Some of the multinucleate erythroblasts displayed a variety of ultrastructural abnormalities, including marked differences in the appearances of the individual nuclei within the same cell. The marrow cells gave a normal deoxyuridine-suppressed value indicating that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. The rates of incorporation of 14C-glycine and 14C-adenine into both the DNA and RNA of bone marrow cells were within the normal range. Furthermore, the average rate of elongation of newly-synthesised, 3H-thymidine-labelled daughter DNA strands, assessed by hydroxyapatite chromatography of alkali-denatured DNA was found to be normal. The results suggest that there is no impairment of DNA replication in the majority of the erythroblasts and that the abnormality of erythropoiesis resulted from disturbances during mitosis and the G2 phase.     

Myelotoxicity of serum and spinal fluid in multiple sclerosis: a critical assessment

Explants of neonatal rat cerebellum have been cultured on rat-tail collagen coated cover-slips for 2–4 weeks under conditions which yielded well myelinated nerve fibres suitable for testing myelotoxicity of serum. Eighty-four per cent of twenty-five acute multiple sclerosis serum samples were myelotoxic, as opposed to 62% of twenty-six sera from cases of motor neurone disease. Twenty-four per cent of thirty-four normal sera also showed distinct myelotoxicity. The difficulties in setting up and interpreting tests for in vitro demyelinating activity of serum are discussed. Six spinal fluids from acute cases of multiple sclerosis were without activity. It is concluded that although myelotoxicity exists in most samples of serum from acute multiple sclerosis, it is not limited to such subjects and that its high incidence in motor neurone disease sera indicates that it may well be a consequence of myelin destruction rather than a primary factor in its causation.     

Detection and characterization of DNA-anti-DNA complexes in a patient with systemic lupus erythematosus.

DNase digestion of SLE serum, with consequent release of bound DNA antibody has been proposed as a method for the direct demonstration of circulating DNA-anti-DNA complexes. In the present studies on the serum of a girl with active SLE nephritis, circulating DNA-anti-DNA complexes were demonstrated at the precise time of relapse of SLE nephritis. Ultracentrifugation showed that these complexes were of low molecular weight.     

Rapid inhibition of DNA synthesis in hepatocytes from regenerating rat liver by serum from patients with fulminant hepatic failure.

The acute effects of serum from patients with fulminant hepatic failure (FHF) on isolated hepatocytes from normal and regenerating rat livers were investigated. DNA and protein synthesis monitored by following the incorporation of [6-3H]-thymidine and [U-14C]-1-leucine into acid-precipitable material was accelerated in hepatocytes from regenerating livers. A specific inhibitory effect of FHF serum on DNA synthesis in hepatocytes from regenerating livers was found. DNA and protein synthesis was inhibited in normal rat hepatocytes by normal serum, the inhibition being less with FHF serum. Cell integrity assessed by leakage of lactate dehydrogenase was not affected by normal or FHF serum. These findings may explain the reduced rate of hepatic regrowth in patients with FHF. Identification of the substances involved will assist in the design of artificial liver support systems and may improve prognosis in this condition.     

Arterial myogenic properties of the spontaneously hypertensive rat

When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension.     

Neurofibromatous neuropathy in neurofibromatosis 1 (NF1)

Background: Neurofibromatosis 1 (NF1) is a common, autosomal dominant, neurocutaneous disease that is clinically and genetically distinct from the rare condition neurofibromatosis 2 (NF2). Neurofibromatous neuropathy has been regarded as a common feature of NF2, but is an unusual and unexplained complication of NF1. The clinical and histological features of the NF1 neuropathy are distinct from those encountered in NF2. We describe eight patients with a symmetrical polyneuropathy, which has been called neurofibromatous neuropathy

Methods: Clinical assessments, laboratory investigations, neuroimaging, and neurophysiology were undertaken in eight individuals with neurofibromatous neuropathy. None were referred because of neuropathic symptoms. Two subjects underwent sural nerve biopsy and three agreed to mutational analysis.

Results: The patients had an indolent symmetrical predominantly sensory axonal neuropathy and unusually early development of large numbers of neurofibromas. The biopsied nerves showed diffuse neurofibromatous change and disruption of the perineurium. Two patients developed a high grade malignant peripheral nerve sheath tumour. Disease causing mutations were detected in two individuals and molecular studies did not reveal any whole gene deletions.

Conclusions: Neurofibromatous neuropathy occurred in 1.3% of 600 patients with NF1. Its cause may be a diffuse neuropathic process arising from inappropriate signalling between Schwann cells, fibroblasts, and perineurial cells.

     

Papillomavirus and c-myc antigen expression in normal and neoplastic cervical epithelium.

Cervical punch biopsy specimens or brushings were collected from 33 patients with cervical human papilloma virus (HPV) infection, cervical intraepithelial neoplasia (CIN), or invasive cervical carcinoma, and from eight control patients with recent normal cervical cytology. Prostatic chippings obtained from six men with benign prostatic hypertrophy were used as further controls. Biopsy specimens and brushings were assayed by flow cytometry for c-myc oncogene antigen and papillomavirus antigen expression and rate of cell division (by measuring DNA content). Results obtained from analysis of specimens and brushings were similar in terms of c-myc antigen and total DNA content, but when the percentages of nuclei from biopsy and brush specimens staining positively with antibody to papilloma viral antigens were compared, brush specimens gave consistently higher percentages than biopsy specimens. More specimens from normal epithelium were c-myc antigen positive (five of eight, (63%) than specimens from CIN II or III (two of 10, 20%), or invasive carcinoma (0%). No association was found between c-myc antigen expression and cell division. HPV antigen positive specimens were found to contain more dividing cells than negative specimens.     

A statistical analysis and comparison of soma diameter spectra for classical neurones from different regions of the cat retinal ganglion cell layer

Multimodal soma diameter spectra for neurones of the cat retinal ganglion cell layer have been represented by three subpopulations of independent, normal diameter distribution. Recurrent computation according to the technique of Vibert and Caille (1978) has extracted best fit populations for samples from various regions of central and peripheral retina. The model subpopulations from all these regions did not differ significantly in their relative proportions or variance. Significant progressive variation between subpopulations representing different regions of retina were observed only in the mean diameter of the and mode cells. The parameters of the mode population were statistically uniform across the retina. The cat retina thus appears to be more homogeneously organized than has been suggested elsewhere.