The Changing Profile of Patients in a Geriatric Medicine Led Memory Clinic over 12 Years.

OBJECTIVES: Memory clinics play an important role in enabling early dementia diagnosis and intervention. Few studies have investigated the changing patient profiles at memory clinics over time. We studied the trend of patient characteristics in a geriatric medicine-led memory clinic over 12 years to improve services and care to meet their needs. SETTING AND PARTICIPANTS: Data from 2340 first-visit patients seen at a memory clinic from 2005-2017 were extracted from a registered database and analysed. DESIGN: ANOVA, Pearson chi-square and non-parametric tests were used to describe and compare between patients with dementia (PWD) and patients with no dementia (PND). MEASUREMENTS: Data included diagnoses of dementia and mild cognitive impairment, age, education, MMSE scores and comorbidities. RESULTS: Patients averaged 77.2 ± 8.3 years of age with mean MMSE score of 16.2 ± 6.7. Those diagnosed with dementia were older (78.3 ± 7.9 years) and almost half (48.4%) had moderate or moderately severe dementia (FAST 5-6). Over time, there was a growing proportion of patients with mild cognitive impairment (MCI) and mild Alzheimer's dementia. Many PWD had co-morbidities of hypertension (65.9%), hyperlipidemia (55.1%), diabetes (33.5%) and 28.4% were frail. CONCLUSIONS: The findings call for services to better diagnose and manage patients at the earlier stages of cognitive impairment and provide holistic interventions for those with frailty and other co-morbidities. The continued rise in number of patients presenting to memory clinics provides impetus to expedite integration of tertiary-based memory clinics with primary and community care providers to better support PWD and their families.

Androgen conjugates in human breast cyst fluids.

Dehydroepiandrosterone sulfate (DHAS) has been measured by radioimmunoassay in 100 breast cyst fluids obtained from 82 women. Values ranged from 1.5 to 1,155 microM with a median of 140 microM. These concentrations are in excess of those for plasma but are comparable or less than values for breast secretions obtained by nipple aspiration. Levels of DHAS in cyst fluid were not significantly affected by age, menopausal status, or parity of the subject or by the volume of cyst fluid obtained. In patients with multiple cysts, DHAS values from cysts aspirated from the same breast on the same data were relatively comparable, but wide variations were frequently observed between cysts aspirated on different occasions from the same breast and between cysts from different breasts of the same patient, whether sampled simultaneously or sequentially. Such variability must complicate comparative studies among women.

Preliminary results of using inertial sensors to detect dementia- related wandering patterns.

We present a solution for detecting dementia-related travel patterns using only inertial sensors. The results and lessons learnt from the experiments on dementia and non-dementia subjects are reported.

Progression of HIV: follow-up of Edinburgh injecting drug users with narrow seroconversion intervals in 1983-1985.

OBJECTIVE: To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. DESIGN AND METHODS: From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group. MAIN OUTCOME MEASURES: The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. RESULTS: The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1, B8, DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8, DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01). CONCLUSIONS: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.

The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection.

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.

Blood transfusion and organ transplantation.

During the last two decades it has been shown that blood transfusion enhances renal allograft survival. Recently, the introduction of cyclosporin A as the leading immunosuppressive agent has generally improved results and the relevance of blood transfusion to organ transplantation is now questioned. This review summarises the vast amount of knowledge on the 'blood transfusion effect in renal transplantation', and we cite important clinical studies of this topic to illustrate the various theories regarding the immune mechanisms responsible for these effects. We draw attention to the other immunomodulatory properties of blood transfusion which may be related to those associated with transplantation. In particular, we examine the possibility that perioperative blood transfusion may have a detrimental effect on the survival of cancer patients.

Applications of intravenous immunoglobulin in haematology.

Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir. Intriguingly, IVIgG appears to moderate the severity of GVHD in adult transplant recipients. IVIgG has short term efficacy in most patients with ITP but, as long term remissions are uncommon, it has become necessary to be more selective in the use of IVIgG in this disorder. The response to IVIgG in other immune-mediated cytopenias is similar with generally transient improvement but also with occasional spectacular cures. The treatment of the acquired haemophilias with IVIgG has yielded in vivo and vitro evidence to support the idiotype-antiidiotype theory of IVIgG immune-modulation and has also demonstrated significant differences in the sensitivity of coagulation factor autoantibodies and alloantibodies to IVIgG therapy. IVIgG has several roles in pregnancy related disorders, including the management of both mother and fetus in ITP during pregnancy, the antenatal and postnatal management of platelet alloimmunisation and also in the management of severe rhesus isoimmunisation. IVIgG is safe and well tolerated. The expense of this therapy should be balanced against the likely gains and the overall costs of alternative approaches.

Measurement of circulating immune complexes by radioimmunoassay of immunoglobulin in high molecular weight fractions.

A method for detecting circulating immune complexes is described based on radioimmunoassay of IgG following the rapid separation of immune complexes from monomeric IgG on short columns of Sephacryl S-300. Values obtained using sera from patients with immune complex associated diseases were distinctly higher than those obtained with sera from healthy control subjects. The same serum samples were assayed by 3 other methods for detecting immune complexes; significant correlation was obtained.

Immunological studies on the cerebrospinal fluid in neurological sarcoidosis.

The rate of intrathecal IgG synthesis and the degree of permeability of the blood-brain barrier in 5 patients with sarcoidosis involving the central nervous system are described. Intrathecal IgG synthesis was unusual but increased leakiness of the blood-brain barrier was common in these patients; a finding which may help differentiate such cases from patients with multiple sclerosis.

HLA antigen frequencies in children born to HIV-infected mothers.

Tissue-typing for HLA-A, B, and DR antigens was carried out on 53 babies, 47 of them unrelated, born to mothers known to be HIV-infected from intravenous drug usage or sexual contact with drug users. These babies were followed up to assess whether HLA phenotype was associated with vertical transmission of HIV infection or disease progression. Of the 47 unrelated babies, eight became infected with HIV. The frequency of HLA-DR3 was three times higher in the HIV-positive infants compared to the HIV-negative infants (43 per cent vs 15 per cent) in our study population. Conversely, HLA-A3 was three times less common in the HIV-positive infants (12.5 per cent vs 42 per cent). A comparison of HLA antigens between our study group babies and babies born to healthy mothers unselected for HIV status revealed higher proportions of HLA-B18, B7, and DR2 in the study group. Moreover, the combination, A3, B7, DR2 was four times commoner in our study population relative to controls (RR = 3.9; p less than 0.003), but was found only in babies who were not HIV infected. The combination A1, B8, DR3, in contrast, was found less often than expected in our study group (RR = 0.39) and was disproportionately represented amongst the infected babies. We have observed an unexpectedly low (6 per cent) mother-to-infant transmission rate of HIV among prospectively studied intravenous drug users. We speculate that the unusually high ratio of the common antigen combinations (often halotypes), A3, B7, DR2 to A1, B8, DR3 in this population may be contributory.

Milk protein concentrations in galactorrhoeic mammary secretions.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

Milk protein concentrations in the mammary secretions of non-lactating women.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA and IgG) or single radial immunodiffusion (lactoferrin) in the mammary secretions of seven healthy non-lactating subjects and eight patients with breast disease. IgA and IgG were detected in all samples of breast secretion (whether from normal or diseased breasts) and the concentrations observed were very similar to those in post-partum colostrum and milk. However, because the volume of secretion obtained was very small compared with colostrum and milk, total IgA synthesis by the non-lactating breast is very much less than in the lactating breast. The IgA detected in the mammary secretions was demonstrated to be secretory IgA by gel filtration and it is therefore suggested that the secretory immune system is functional in the non-lactating breast.

Lack of specificity for antibodies to double stranded DNA found in four commercial kits.

Four commercially available kits (three enzyme linked immunosorbent assays and one modified Farr radioimmunoassay) were compared for their ability to detect specifically autoantibodies to double-stranded DNA (dsDNA) using 66 patient sera. This was assessed by comparing the results of the kits with those from an ELISA specifically measuring antibodies against highly purified dsDNA, single-stranded DNA (ssDNA), native DNA and histones. The RIA and two of the ELISAs seemed equally efficient at detecting antibodies to dsDNA, but all three also detected anti-ssDNA (the RIA being particularly bad for this). The need for highly purified dsDNA was clearly shown. The results obtained with one ELISA did not correlate with any variable investigated in this study. A total of 220 sera were assayed with the IDS RIA, of which 130 were recorded as positive. Of these, 50 sera seemed to contain no identifiable autoantibodies. This very high false positive rate may be due, at least in part, to precipitation of nonspecifically bound labelled DNA.

Use of serum from patients with polycythaemia or haemochromatosis for laboratory external quality assurance exercises.

Some External Quality Assessment Schemes (EQAS) require large volumes of human serum. During a one year period, 595 units of blood were obtained from 87 patients with haemochromatosis and polycythaemia, who underwent therapeutic venesection at the Edinburgh and South East Scotland Blood Transfusion Service. Serum from 59% of these donations was used in the EQAS for peptide hormones and related substances. The cost of the serum collection was 109 pounds/litre, but was only 33 pounds/litre of serum if the cost of the actual venesection was excluded. Results from tests on the sera were satisfactory in a variety of immunoassays for several different hormones. EQA schemes with requirements for large volumes of serum should consider therapeutic venesection as a cost effective means of obtaining serum.

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease.

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).

Characterisation of mouse monoclonal antibodies produced by immunisation with a single serotype component of a polyvalent Pseudomonas aeruginosa vaccine.

Mouse monoclonal antibodies raised by immunisation with a protective antigen extract from Pseudomonas aeruginosa serotype 1 varied in immunoglobulin isotype, in passive protective properties against infection by homologous P. aeruginosa serotype 1, and in cross-reactions in ELISA against antigen preparations from 15 other P. aeruginosa serotypes. All monoclonal antibodies with specificity in ELISA for the immunising antigen gave some degree of protection to mice against lethal infection by the homologous P. aeruginosa serotype. The IgG antibodies were more protective than the IgM antibodies.

Developmental changes in the fatty acids of rat uterus and the influence of dietary essential fatty acids.

The effect of age on uterine fatty acid composition was studied in rats fed diets of differing fatty acid composition. Uteri of newly weaned 23-day rats had a higher fatty acid content and a higher proportion of short-chain (less than or equal to C18) fatty acids. Higher incorporation of C less than or equal to 18 fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats compared with adult 240-day rats was detected. Uterine NL incorporated predominantly C less than or equal to 18 fatty acids which may be an important metabolic energy store in developing uterine tissue. Incorporation of C less than or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In contrast, there was selective retention of arachidonic acid (AA) and docosahexanoic acid (DHA) throughout uterine development. An effect of dietary EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked retention of uterine AA when dietary supplies of n-6 EFA were low, but the total AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the three diet groups, and a constant content of AA, EPA and DHA was maintained throughout uterine development, regardless of diet. The degree of n-3 substitution achieved in this study inhibited uterine release of PG and parturition in adult rats.

The influence of dietary essential fatty acids on uterine C20 and C22 fatty acid composition.

The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition.