Unequal distribution of cognitive deficits in vascular dementia--is this a valid criterion in the ICD-10?

OBJECTIVE: To investigate the appropriateness of the ICD-10 criterion for vascular dementia which requires unequal distribution of deficits between different domains of cognitive function. DESIGN: Cross-sectional comparative study. SETTING: Referrals to a specialist memory clinic in Sheffield and a community sample of patients from a general practice population in Melton Mowbray. METHOD: The CAMCOG part of the Cambridge mental disorders of the elderly examination (CAMDEX) was assessed for 131 Sheffield subjects and 396 Melton Mowbray subjects to examine both total variability and differences between individual subscale items. Depression was also examined as this was a potential confounding factor. RESULTS: After adjustment for age, sex and depression scores, there were no significant differences between vascular dementia subjects and Alzheimer's disease subjects at either centre for total variability of cognitive deficits and little difference between diagnoses for individual subscale items. In Sheffield, subjects with vascular dementia had significantly higher depression scores compared to those with Alzheimer's disease. CONCLUSIONS: The usefulness of the concept of unequal deficits as a diagnostic criterion for vascular dementia in routine clinical practice is doubtful.

Factors associated with vascular dementia in an elderly community population.

OBJECTIVE: Examination of associated factors for vascular dementia in comparison with Alzheimer's disease and a non-demented control population. SETTING: A semi-rural geographically defined population, in Melton Mowbray and the surrounding area, consisting of elderly patients aged 75 and over from a 13-doctor general practice. METHOD: 438 subjects, sampled according to results of initial screening with the Mini-Mental State Examination (MMSE), were examined using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), which was also used to classify the subtypes of dementia. RESULTS: 34 subjects had vascular dementia, 222 had Alzheimer's disease and 140 were non-demented according to the clinician's diagnosis based on the CAMDEX criteria. Significant factors associated with vascular dementia, when compared to the Alzheimer's disease and non-demented groups, were family history of stroke and diabetes. Stroke was also significant, but this factor is one of those defining the criteria for diagnostic grouping. There were no significant differences between groups for falls, heart attack, hypertension, head injury, substance abuse or lipid levels. CONCLUSION: The results are broadly consistent with the published literature and emphasize the importance of diabetes as a key risk factor for vascular dementia.

Cholesterol and mental disorder.

BACKGROUND: Cholesterol plays an important part in cellular structure and function and changes in serum levels may affect neurotransmission in the central nervous system. METHOD: A MEDLINE literature search was made covering the period 1990-95 with systematic searching of citations from the articles identified. Representative articles were selected, focusing on those aspects which had not been thoroughly reviewed elsewhere, namely suicidal ideation, depression, personality and schizophrenia. RESULTS: Lowering cholesterol levels have been associated with an increase in violent deaths in cardiovascular primary prevention studies. However, altered cholesterol levels have also been reported in relation to other psychiatric disorders. CONCLUSION: There is substantial evidence that serum cholesterol levels may be associated with variations in mental state or personality. Further work is needed to clarify this and to elucidate the mechanisms involved.

The effect of a topical non-steroidal anti-inflammatory drug on the development of experimental gingivitis in man.

24 healthy volunteers abstained from tooth-cleaning for 17 days. Parameters of gingival health were recorded on days 1 and 17. On days 4, 6, 8, 11, 13 and 15, each volunteer randomly received, on a double-blind basis, 100 ml of 10 mM flurbiprofen solution in buffered preservative to one upper quadrant of the mouth. The contralateral quadrant received preservative only. Applications were made using a pulsed jet irrigating system. Gingivitis developed in all patients and there were no significant differences between the treatments for gingival index or pocket probing depths. When gingival health was re-established, 4 volunteers had a further 3 irrigations of flurbiprofen at intervals of 2 days. Plasma levels of flurbiprofen were determined after the 1st and 3rd irrigations. Assays showed that the drug was present in the plasma of all 4 subjects (range 0.2-0.7 micrograms/ml). Gingival health was re-established in 6 further volunteers from the original study. They then abstained from toothbrushing for 17 days, during which one maxillary quadrant was irrigated with the buffered preservative solution. The irrigations were made on the same basis as in the original study. Gingivitis again developed in these quadrants, although when the results were compared to the equivalent data from the first investigation, significantly greater median values for probing pocket depths and gingival indices were found in the latter study. Therefore, it appears that systemic absorption of flurbiprofen may have reduced the severity of the developing inflammatory lesions.

Augmentin compared with oxytetracycline for chest infections in general practice.

Augmentin and oxytetracycline were compared in the treatment of chest infections in general practice in an investigator-blind study of 748 patients randomly allocated to 7 days' treatment with standard doses of either Augmentin or oxytetracycline. Significantly more patients treated with Augmentin had a good overall response to therapy both at day 7 (P less than 0.001) and at day 14 (P less than 0.01). The differences between treatments were less marked for individual signs and symptoms of lower respiratory tract infections, due to smaller numbers of patients with any particular symptom. Augmentin, however, was significantly more effective than oxytetracycline in the resolution of chest pain at day 7 (P less than 0.025) and cough at day 14 (P less than 0.005). Sputum purulence was also cleared more effectively by Augmentin by day 14 (P less than 0.001). Both treatments were well tolerated, with no significant difference between treatments in the small number of adverse events. Augmentin has been shown to be an effective, well tolerated treatment for chest infections, superior to oxytetracycline in efficacy and possibly in speed of resolution of clinical symptoms.

Paracetamol plus metoclopramide ('Paramax') as an adjunct analgesic in the treatment of arthritis.

In a 12-week crossover study, a formulation of paracetamol (500 mg) and metoclopramide (5 mg) was compared with paracetamol (500 mg) alone for adjunct analgesia in 39 patients with arthritis. Most were on stabilized therapy with anti-inflammatory drugs and all had a history of a tendency to develop gastro-intestinal symptoms. Patients were allocated at random to receive 2 tablets 3-times daily of either treatment for 6 weeks and were then crossed over to the alternative treatment at the same dosage for a further 6 weeks. The results showed that the paracetamol/metoclopramide formulation appeared more effective as an analgesic than paracetamol alone and gave a highly significant reduction in the mean score for upper gastro-intestinal symptoms when compared with paracetamol. There were no side-effects associated with the metoclopramide component. It is concluded that the paracetamol/metoclopramide formulation is a suitable adjunct analgesic for osteoarthritis and rheumatoid arthritis in those patients prone to gastro-intestinal disturbance.

Purification, properties, and immunohistochemical localisation of human brain 14-3-3 protein.

A protein has been purified from human brain that appears to be the human equivalent of bovine 14-3-3 protein. On polyacrylamide gel electrophoresis the protein migrates as a faster major component, termed 14-3-3-2 protein, and a slower minor component, termed 14-3-3-1 protein, which consists of approximately 12% of the total protein. Both 14-3-3-1 and 14-3-3-2 have a native molecular weight of approximately 67,000. 14-3-3-2 appears to have the subunit composition alpha beta; 14-3-3-1 has the composition beta'beta'. Peptide mapping with Staphylococcus aureus V8 proteinase shows that alpha and beta subunits are unrelated but the beta and beta' subunits show some common peptides. Immunoperoxidase labelling shows that 14-3-3 is localised in neurones in the human cerebral cortex. 14-3-3 shows no enolase, creatine kinase, triose phosphate isomerase, ATPase, cyclic nucleotide-dependent protein kinase, or purine nucleoside phosphorylase activity. 14-3-3 does not bind calcium and does not appear to be related to calmodulin, calcineurin, tubulin, neurofilament proteins, clathrin-associated proteins, or tropomyosin. The functional significance of this neuronal protein remains obscure.

Human 14-3-3 protein: radioimmunoassay, tissue distribution, and cerebrospinal fluid levels in patients with neurological disorders.

An antiserum to human 14-3-3 protein has been produced in rabbits. The protein was a poor antigen and attempts to improve immunogenicity were unsuccessful. A radioimmunoassay was developed using the antiserum, 125I-14-3-3-2, and unlabelled 14-3-3-2 as standards. The assay had a sensitivity limit of 2.5 ng.ml-1. The minor component of human 14-3-3 protein (14-3-3-1 protein) cross-reacted to approximately 10% in the assay. Human tissues were surveyed for 14-3- protein by two-dimensional electrophoresis and by radioimmunoassay. Two-dimensional electrophoresis showed a 14-3-3 protein complex in brain, intestine, and testis, but not in other tissues. Radioimmunoassay showed that although brain had the highest concentration of 14-3-3 (13.3 microgram.mg-1 soluble protein), immunoreactivity was present in all tissues, with the concentration in intestine and testis approaching 50% of the brain level. Lower levels (less than 1.0 microgram.mg-1 soluble protein) were seen in liver, kidney, skeletal muscle, and erythrocytes. The immunoreactivity present in tissues other than brain showed the same molecular weight and charge characteristics and authentic 14-3-3 protein. The radioimmunoassay also detected 14-3-3 protein in serum (50 ng.ml-1) and in CSF (5-130 ng.ml). The immunoreactivity present in CSF appeared to be intact 14-3-3 protein. CSF 14-3-3 levels were measured in 82 patients with various neurological disorders. Measurements of this protein did not appear sufficiently discriminating to be of diagnostic value.