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Biomedical subjects

P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 217 records · Page 12Linked to original sources
PubMed1991

Open access clinic providing HIV-I antibody results on day of testing: the first twelve months.

OBJECTIVES: To determine the sociodemographic profile, risk category, and prevalence of HIV-I infection among people attending a clinic providing counselling, medical advice, and results of HIV-I antibody testing on the day of consultation; to determine the stage of infection and peripheral blood CD4 cell count among attenders with detectable HIV-I antibodies. DESIGN: Analysis of prospectively collected data for the 12 months from March 1989. SETTING: Same day testing clinic run by the HIV/AIDS team at an urban teaching hospital. PATIENTS: 561 consecutive people choosing to attend and proceeding to HIV-I testing. RESULTS: The demand for the service caused it to run to capacity within six months. The median age of those attending was 28 years and 65% (364 patients) were male. The overall prevalence of HIV-I infection was 3.9% (22 patients). The greatest prevalence was in men reporting their primary risk as homosexual contact (11.9%, 13/109). The median CD4 cell count in the 22 patients who had detectable HIV-I antibodies was 0.31 x 10(9) cells/l (normal range 0.5 x 10(9)/l to 1.2 x 10(9)/l). Twenty of these patients were asymptomatic (Centers for Disease Control stages II or III), 14 had CD4 cell counts below 0.5 x 10(9)/l. CONCLUSIONS: There is a recognisable demand for a service providing rapid results of HIV-I antibody testing in this setting. The overall seroprevalence of 3.9% is comparable with the 5.8% reported from freestanding clinics in the United States. Most patients with HIV-I antibodies detected in this way are asymptomatic but could benefit from early medical intervention because of low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cytomegalovirus excretion after bone marrow transplantation cannot be predicted from the pre-transplant level of IgG antibodies.

The relationship of pre-bone-marrow transplant recipient and donor cytomegalovirus (CMV) antibody level to post-transplant recipient CMV excretion was investigated. CMV excretion was found to be related to pre-transplant recipient serological status, but not to level of antibody. This therefore contrasts with herpes simplex virus (HSV), for which pre-transplant antibody level in recipients predicts post-transplant HSV excretion.

Adolescent↗
PubMed1991

Advances in the prevention and treatment of cytomegalovirus infection in hospital patients.

The incidence of cytomegalovirus (CMV), a common pathogen for hospital patients, can be reduced by providing virus-free blood products. The virus can also be transmitted via solid organ allografts and the efficacy of matching donor and recipient for improving overall patient survival needs formal evaluation. Patients at risk of future disease can be detected by surveillance cultures, whose prognostic value is good for bone marrow transplant recipients; formal evaluation in other groups of patients is required. This is particularly important now that ganciclovir and foscarnet are licensed for the therapy of life-threatening CMV infections and other therapies are available on an investigational basis. Resistance to ganciclovir has been described and is likely to be an increasing problem. Placebo-controlled trials have shown that prophylaxis with alpha-interferon, immunoglobulin or high-dose acyclovir can significantly reduce CMV infection and CMV disease.

Antibodies, Monoclonal↗
PubMed1991

Population dynamics of HIV within an individual after treatment with zidovudine.

A new mechanism is proposed for the apparent breakthrough of HIV that occurs approximately 6 months after the commencement of therapy with zidovudine (AZT). Using a simple mathematical model of the interacting population dynamics of HIV and its major host cell in the circulation (the CD4+ lymphocyte), predicted patterns of HIV plasma viraemia in the weeks following treatment with zidovudine are generated. These are in close agreement with observed patterns despite the fact that the model contains no mechanisms for the development of drug-resistant strains of virus. It is suggested that the patterns of viral abundance observed during the first 6 months after treatment may be the result of non-linearities in the interactions between HIV and CD4+ cells, and that it is only after the first post-treatment burst of viral production that drug resistance plays an important role.

AIDS-Related Complex↗
PubMed1991

p24 antigenaemia, CD4 lymphocyte counts and the development of AIDS.

A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Use of the polymerase chain reaction to analyse sequence variation within a major neutralizing epitope of glycoprotein B (gp58) in clinical isolates of human cytomegalovirus.

The heterogeneity of low passage human cytomegalovirus (HCMV) strains was determined by HindIII typing of 28 clinical isolates from transplant patients. These data have shown that, in general, each patient's strain has a unique restriction profile, usually comprising combinations of HindIII sites present in one or more of the tissue culture-adapted strains AD169, Towne and Davis. To map sequence changes in a more refined manner we performed detailed analyses of 33 low passage clinical isolates, including those aforementioned, analysing a sequence within glycoprotein B containing a major neutralizing epitope. A 149 bp sequence containing the epitope (amino acids 608 to 625) was amplified using the polymerase chain reaction, the products were cloned and their DNA sequence was determined. Comparison of the DNA and deduced amino acid sequences with those of HCMV strain AD169 revealed that there was a high degree of conservation of the epitope between the 33 clinical isolates. However 10 of the isolates possessed silent mutations and three isolates contained mutations producing amino acid changes within the neutralizing epitope. The possible functional significance of these changes is discussed.

Amino Acid Sequence↗
PubMed1991

Hepatitis C antibody assay in a longitudinal study of haemophiliacs.

Stored sera from 28 patients with inherited coagulation disorders who had developed non-A non-B hepatitis (NANBH) following a first exposure to clotting factor concentrates and 15 similar, but unmatched, patients who had received blood products but had normal transaminases on sequential testing were tested using the Ortho enzyme-linked immunosorbent assay (ELISA) anti-HCV assay. Twenty-seven of the 28 patients with NANBH were anti-HCV positive after exposure. In 10 of those in whom dates of first exposure and seroconversion were well-defined, the median time interval to NANBH was 4 weeks (range 1-7) and to anti-HCV seroconversion was 11 weeks (range 7.5-14.5). None of the 15 patients without NANBH developed anti-HCV. This first generation Ortho ELISA anti-HCV assay showed 96% sensitivity and 100% specificity and has potential use as an adjunct in the surveillance of new clotting factor products.

Adolescent↗
PubMed1991

Congenital and maternal cytomegalovirus infections in a London population.

OBJECTIVE: To determine if women at risk of having babies infected with cytomegalovirus (CMV) can be identified antenatally. DESIGN: Prospective serological and demographic study of pregnant women and virological study of their newborn infants. SETTING: Teaching hospital in London. SUBJECTS: 3315 pregnant women and 2737 of their babies. MAIN OUTCOME MEASURES: Quantitative detection of CMV IgG antibodies; qualitative detection of CMV IgM antibodies; demographic characteristics of mothers; qualitative and quantitative titration of CMV viruria in newborn. RESULTS: Congenital CMV infection was found in nine newborn babies (0.33%) two of whom had symptoms. Serological testing of the nine mothers showed four primary and five recurrent infections; both of the symptomatic children were born in the latter group. Testing for CMV specific IgM antibodies or quantitation of IgG antibodies in early pregnancy sera could not differentiate those women at risk of giving birth to babies infected or damaged by CMV from the rest of the population. Quantitation of viruria confirmed that those babies most at risk of CMV disease have the highest titres of CMV. CONCLUSIONS: (i) Since laboratory tests in pregnant women cannot reliably identify fetuses at risk of disease, screening for asymptomatic maternal infection coupled with termination of pregnancy cannot be recommended. (ii) Since 'immune' women can still give birth to babies affected by CMV, we propose that future CMV vaccines should be used to immunize children with the aim of eradicating CMV infection in preference to selective immunization of sero-susceptible females.

Adolescent↗
PubMed1990

HIV susceptibility conferred to human fibroblasts by cytomegalovirus-induced Fc receptor.

The main receptor for the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) on T and B lymphocytes, monocytes and macrophages is the CD4 antigen 1-3. Infection of these cells is blocked by monoclonal antibodies to CD4(1,2) and by recombinant soluble CD4(4-9). Expression of transfected CD4 on the surface of HeLa and other human cells renders them susceptible to HIV infection 10. HIV-antibody complexes can also infect monocytes and macrophages by means of receptors for the Fc portion of immunoglobulins (FcR)11-13), or complement receptors 14,15. The expression of IgG FcRs can be induced in cells infected with human herpes viruses such as herpes simplex virus type 1 (HSV-1)16,17 and human cytomegalovirus (CMV)18-21. Here we demonstrate that FcRs induced by CMV allow immune complexes of HIV to infect fibroblasts otherwise not permissive to HIV infection. Infection was inhibited by prior incubation with human IgG, but not by anti-CD4 antibody or by recombinant soluble CD4. Once HIV had entered CMV-infected cells by means of the FcR, its replication could be enhanced by CMV transactivating factors. Synergism between HIV and herpes viruses could also operate in vivo, enhancing immunosuppression and permitting the spread of HIV to cells not expressing CD4.

Base Sequence↗
PubMed1990

Dihydropteridine reductase activity in eluates from dried blood spots: automation of an assay for a national screening service.

We describe the automation, using a Cobas Bio centrifugal analyser, of a method for dihydropteridine reductase (DHPR) assay in eluates from dried blood spots. This is used as part of a routine screening service of neonates with hyperphenylalaninaemia in the United Kingdom. Automation reduced reagent volumes and analysis time by about 80% and improved the precision of the assay. Relating DHPR activity to haemoglobin concentration of the eluate further improved the precision of the assay and removed some differences in 'apparent' DHPR activity between samples from different countries and different age groups.

Age Factors↗
PubMed1990

Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease.

Experiments are described in which the benzodiazepine portion of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor and the muscarinic cholinergic receptor were investigated in Parkinson's disease and control brains. Tritiated flunitrazepam and tritiated quinuclidinyl benzilate (QNB) were used to locate and quantify the receptors by autoradiographic and homogenate binding techniques. Densitometric analysis of autoradiographs of the basal ganglia allowed comparison of receptor densities in the post-mortem control and parkinsonian tissue, while homogenate binding experiments gave information concerning receptor affinity and maximum binding capacity. The results indicate that: 1) Binding of flunitrazepam to the benzodiazepine receptor is reduced in the lateral segment of the globus pallidus in Parkinson's disease. This suggest that the GABA-ergic pathway from the putamen to the lateral pallidal segment is overactive in Parkinson's disease. 2) Binding of QNB to the cholinergic receptors of the medial pallidal segment is increased in Parkinson's disease. This finding suggests underactivity of the cholinergic pathway from the pedunculopontine nucleus of the medial pallidal segment. 3) Binding of these ligands in the caudate and putamen of Parkinson's disease is not significantly different from controls. We reviewed the literature concerning the activity of these projections in parkinsonian conditions assessed by different methods and discuss here their implications for the pathogenesis of parkinsonian symptoms.

Aged↗
PubMed1990

Virus infections in patients with AIDS.

Virus infections are common in patients with acquired immune deficiency syndrome (AIDS). Viruses can have two distinct relationships with human immunodeficiency virus (HIV); they can be opportunists if the second virus takes advantage of decreased immune function in the host or they can act as co-factors to accelerate the rate at which AIDS develops. Viruses acting as opportunists may cause no symptoms or may be life-threatening. Several, including herpes simplex, varicella zoster, cytomegalovirus and Epstein-Barr virus, can be treated with antiviral agents. Before concluding that a virus can act as a co-factor for HIV, several other possible relationships must be excluded including opportunism, co-parameters of lifestyle and prognostic markers. Studies in vitro may suggest which viruses are potential co-factors but clear evidence can come only from carefully defined cohorts of patients. Recent evidence showing that cytomegalovirus can meet these criteria is presented.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Other common types of viral hepatitis and exotic infections.

This chapter discusses two distinct sets of viruses which cause hepatitis. The first include common virus infections which cause mild hepatitis rarely in individuals with normal immunity but which may cause severe life-threatening hepatitis in the increasing number of patients with depressed cell mediated immune responses. The second comprise exotic virus infections which are prevalent in particular geographical areas and which frequently involve the liver with high mortality. For each of these viruses the epidemiology, clinical features, diagnosis and treatment are briefly reviewed.

Adenoviridae Infections↗