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Biomedical subjects

C Loveday

Publications and source records attributed to C Loveday.

At least 73 records · Page 4Linked to original sources
PubMed1993

Changes in circulating immune complexes during the Jarisch Herxheimer reaction in secondary syphilis.

A cohort of 16 patients with early secondary syphilis were recruited to investigate the role of circulating immune complexes in the pathogenesis of the Jarisch Herxheimer reaction. Eleven of 16 patients had a reaction (68.75%) following initial therapy, characterised by rash potentiation, pyrexia, cardiovascular changes and a number of less specific symptoms. Circulating immune complexes were measured by a standard polyethylene glycol precipitation method and a new sensitive conglutinin binding assay that measured the proportion of IgG, IgM and IgA in complexes, in the first 8 hours after initial therapy. In the latter assay, resting levels of IgG (range 46-700 micrograms/ml) and IgM (range 100-410 micrograms/ml) containing complexes were raised in all patients prior to treatment, but levels were not predictive of those who subsequently had a Jarisch Herxheimer reaction. All patients having a reaction demonstrated a mean fourfold or greater rise in IgG (mean rise 712 micrograms/ml; range 180-1506 micrograms/ml) and IgM (mean rise 804 micrograms/ml; range 200-1120 micrograms/ml) containing complexes between two and eight hours after initial therapy. No such effect was seen in the five patients having no reaction or in a control subject. All these results were confirmed using the polyethylene glycol precipitation method for complex detection.

Adult↗
PubMed1993

HIV-1 plasma viraemia quantification: a non-culture measurement needed for therapeutic trials.

Accurate measures of inhibition of virus replication are needed to evaluate the efficacy of antiretroviral agents in large clinical trials. We describe an accurate, economical and rapid method for the direct detection and quantification of cell-free human immunodeficiency virus type -1 (HIV-1) in serum or plasma. The method includes affinity capture of the virus by latex microparticles coated with HIV-1 envelope-specific antibodies, reverse transcription primed by an HIV-1 specific oligonucleotide and amplification by nested PCR of the synthesised cDNA. We show that the method can be applied to large numbers of serum samples, is reproducible and is highly applicable to the monitoring of viral load in HIV-1 infected patients, especially during the investigation of drug efficacy.

Base Sequence↗
PubMed1993

Enzyme-linked immunosorbent assays for the measurement of human immunodeficiency virus, type 1 reverse transcriptase antigen and antibodies.

Enzyme-linked immunosorbent assays (ELISA), using recombinant HIV-1 reverse transcriptase (RT; p66), are described for the measurement of RT antigen and serum antibodies to RT (anti-RT). The ELISA for anti-RT was developed in qualitative and quantitative forms, both were highly specific (100%, 0/859; 99.6%, 3/859), the former was sensitive (100%, 364/364) detecting the highest dilution of a standard high titre anti-HIV-1 RT antibody positive control serum. The latter was less sensitive (97.2%, 354/364) detecting lower dilutions of the antibody control, but had the advantage of producing highly reproducible optical density/concentration curves for the quantification of unknown anti-RT samples. In a cross-sectional study of 191 patients with HIV-1 infection, all patients developed anti-RT antibodies in CDC disease group II and III that declined but persisted in all cases into CDC disease group IV. The RT antigen assay was specific (100%, 0/772) and sensitive detecting 6 to 15 pg/ml of recombinant RT antigen diluted in normal human serum. No cross-reactivity using the RT antibody and antigen assays was seen in sera from 85 patients with current or previous hepatitis B infection or 21 sera from patients with HIV-2 infection. Further, no reactivity was demonstrated with the assays in a cohort of 20 seronegative partners (320 samples) exposed to HIV-1 infection over a 4-yr period. In samples from a patient with documented seroconversion, RT antigen was the first detectable marker of HIV-1 infection and was followed by a prompt anti-RT response. Serum RT antigen disappeared or remained low in most patients during CDC disease group II and III and rarely reappeared with progression to CDC disease group IV. In tissue culture studies RT antigen was detected in supernatant within 12 h (75 pg/ml), gave an initial peak at 36 h (300 pg/ml) and then continued to rise up to 5 days (603 pg/ml), offering a simple, cost-effective alternative to existing methods.

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

The prevalence of human retroviral infections in female patients attending a central London sexually transmitted disease clinic: 1985-1990.

OBJECTIVES: To determine the prevalence of infection with HIV-1, HIV2, HTLV-1 and HTLV-2 in female attenders at a central London sexually transmitted disease clinic in an 8 week period in 1989-1990, and compare it with similar samples studied between 1985 and 1987. DESIGN: Anonymous testing of serum samples from consecutive female patients having routine serological investigation for syphilis. Testing was for clinically important retroviruses, Hepatitis B core antibodies (anti-HBc), and p24 and reverse transcriptase (RT) antigens. Age (in 5 year bands), nationality (in broad geographical zones), diagnosis on the day of presentation, and history of intravenous drug usage were recorded for each patient. Annual gonorrhoea rates were analysed from 1981 to 1990. SETTING: Outpatients of the department of genitourinary medicine. PATIENTS: A total of 850 females attending consecutively and having routine syphilis serology. MAIN RESULTS: The prevalence of anti-HIV-1 in female attenders in 1989-1990 was 0.35% (3/850). Prevalence in the same clinic has remained statistically unchanged since the first female cases were identified in 1986. No cases of HIV-2, HTLV-1 or HTLV-2 were identified, and no early HIV-1 infection evidenced by the presence of p24 or RT antigenaemia was found. Female gonorrhoea rates continued to decline but other STD monthly/annual rates have remained unchanged. CONCLUSIONS: Over the last 5 years prevalence of HIV-1 infection in females in our clinic has remained unchanged and other retroviral infections have remained absent. However, the unaltered rates of other genital infections, their potential role in the heterosexual spread of HIV-1 infection, and the lack of evidence for any major changes in female sexual behaviour suggests there is a need to remain vigilant. This work complements the MRC multicentre, unlinked, genitourinary medicine clinic, anonymous testing programme, and our group will continue to apply this simple methodology to specimens from female attenders to contribute to the surveillance of the evolving HIV-1 epidemic.

Adolescent↗
PubMed1992

Attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus.

A survey was carried out into attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus type 1 (HIV-1) infection associated with clinical situations that would normally have been managed surgically with low operative mortality rates and long median survival times. The survey response rate was 72.4 per cent. In patients with acute valvular insufficiency or with continuing angina despite maximal medical therapy (unstable angina) who were HIV-1 antibody positive, 75.8 and 80.8 per cent, respectively, of surgeons would operate. If the patient had end-stage infection, acquired immune deficiency syndrome (AIDS), 29.7 per cent and 34.7 per cent, respectively, would consider surgical intervention. When asked to perform simple procedures such as open lung biopsy or pleurectomy on a patient with AIDS, more than half of surgeons would operate (52.2 and 65.6 per cent respectively). In patients with operable carcinoma of the lung and asymptomatic HIV-1 infection 52.3 per cent would operate. This fell to 15.0 per cent if the patient had a diagnosis of AIDS. The majority of surgeons (77.2 per cent) felt patients should have an HIV-1 antibody test before operation and this rose to 95.6 per cent if patients were in a high-risk group; 60.2 per cent of surgeons had changed their surgical practice to reduce the risks of blood-borne infection.

Attitude of Health Personnel↗
PubMed1992

A microtitre format point mutation assay: application to the detection of drug resistance in human immunodeficiency virus type-1 infected patients treated with zidovudine.

An assay for the analysis of point mutations in DNA fragments amplified by the polymerase chain reaction is described. The method was applied to the analysis of mutations leading to single amino acid changes in the reverse transcriptase gene of human immunodeficiency virus type-1 that are associated with decreased sensitivity of the virus to the effects of the nucleoside analogue zidovudine. The assay uses a microtitre format allowing large numbers of clinical samples to be analysed, and is a quantitative assay giving information on the relative proportions of wild-type and mutant sequence at the point being analysed. The analysis of mutations in codons 67, 70, 215, and 219 of the RT gene in samples taken at various time points after the commencement of zidovudine therapy shows a high variability in the rate at which these mutations arise and in the proportions of wild-type and mutant sequences observed. The method we describe has wide application to the analysis of other point mutations in clinical or research studies.

Base Sequence↗
PubMed1992

HIV-1 infection and cardiothoracic surgery: the difference in attitudes between consultants and junior surgeons in the United Kingdom.

A postal survey was carried out inviting the opinions of consultant and trainee cardiothoracic surgeons on the subject of operating upon patients who are either HIV-1 antibody positive or suffer from full-blown AIDS. The questionnaire contained both cardiac and thoracic clinical situations, all of which under normal circumstances would be managed surgically with low operative mortality and long median survival. The overall response rate was 72.4%. A significantly greater number of consultants replied compared to juniors, 80% and 51.6%, respectively (P less than 0.001). In both groups, surgeons were more likely to operate upon a patient who was HIV-1 antibody positive than one who had AIDS. There were no significant differences in the replies of consultants and juniors to the clinical scenarios presented. However, a greater number of juniors admitted to modifying their surgical practice in the light of the increasing incidence of HIV-1 infection (P less than 0.001). Routine preoperative HIV antibody testing was advocated by 77.8% of consultants and 75% of juniors and this rose to 95.1% and 97%, respectively, if patients were in the traditionally high risk groups. Four consultants admitted that they were already performing routine preoperative HIV antibody screening. This survey emphasized the real concern amongst cardiothoracic surgeons, irrespective of their grade, about HIV-1 infection and the need for both education and clear policy guidelines to deal with this difficult issue.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Transmission of HIV-1 infection by oroanal intercourse.

We report the cases of two homosexual men, one of whom is believed to have been infected with HIV-1 during oroanal intercourse with the other, his only current sexual partner. Both patients had sero-conversion illnesses with similar symptoms and signs, and of similar duration. The practise of oroanal intercourse is known to be associated with the transmission of enteric infections and has been implicated in the epidemiology of Kaposi's sarcoma. These well-documented cases indicate that HIV-1 may also be transmitted by this route and supports a cautious approach to recommendations regarding "safer" sex.

Adult↗
PubMed1991

Hepatitis C virus: evidence for sexual transmission.

OBJECTIVE: To determined the prevalence of hepatitis C virus infection and associated risk factors in patients attending a genitourinary medicine clinic, as evidence for sexual transmission. DESIGN: Seroprevalence estimated by reactivity in an enzyme immunoassay for antibodies to C100 protein with supplementary testing with a recombinant immunoblot assay and an assay for hepatitis C virus RNA. SETTING: Outpatient genitourinary medicine clinic in central London. PATIENTS: The panel of 1046 serum samples was from 1074 consecutive patients attending the clinic during November and December 1987 and having blood taken for routine testing for syphilis. Before samples were anonymised demographic and risk factor information was extracted from the clinic notes. Samples had already been tested for antibody to HIV-I and antibody to hepatitis B core antigen. MAIN RESULTS: Significantly more homosexual subjects than heterosexual subjects were positive for hepatitis C antibody determined by enzyme immunoassay alone (19/275 (6.9%) v 8/771 (1.0%), odds ratio 7.14, p less than 0.0001) and also when reactive serum samples were also tested by recombinant immunoblot assay (6/270) (2.2%) v 3/770 (0.4%), odds ratio 5.88, p less than 0.02). There were also significant associations in patients positive for hepatitis C antibody with positivity for antibodies to HIV and to hepatitis B core antigen, lifetime number of sexually transmitted diseases (homosexual men only), and age (all groups combined). Most patients whose serum samples contained specific antibodies to hepatitis C virus were viraemic. CONCLUSIONS: The study provides strong evidence for the sexual transmission of hepatitis C virus. Assays derived from other gene products are desirable to investigate the specificity and sensitivity of the enzyme immunoassay for C100 antibody as a marker of hepatitis C virus infection.

Adolescent↗
PubMed1991

Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy.

Cell-free human immunodeficiency virus type-1 (HIV-1) was precipitated from archival serum with polyethylene glycol (PEG), and HIV-1 RNA was detected and quantified by reverse transcription and amplification in a nested polymerase chain reaction (PCR). The assay of end-point dilutions cDNA in nested PCRs allowed an estimation of the minimum RNA copies per unit volume of serum. RNA titres correlated with the classification of HIV-1 infection by CDC disease groups (30 patients). The geometric mean titres of HIV-1 serum RNA from patients grouped by disease stage gave minimum estimates of 340 and 400 virions per millilitre of serum in CDC groups II and III (n = 6 and 10, respectively) and 4,240 virions per millilitre in CDC group IV (n = 14). An overall fall in viral titre measured in this way was observed in 3 patients during zidovudine treatment. HIV-1 titres increased in a further 4 patients when therapy was interrupted, stopped, or complicated by secondary infection.

Base Sequence↗
PubMed1991

Sclerosing cholangitis rapidly following anti-HIV-1 seroconversion.

A 22 year old man developed sclerosing cholangitis within two months of documented HIV-1 seroconversion. Sclerosing cholangitis should be included in the differential diagnosis of causes of abdominal pain and raised alkaline phosphatase enzyme levels in HIV-1 antibody positive patients without established CDC stage IV disease.

AIDS Serodiagnosis↗
PubMed1990

Response of serum p24 antigen and antibody to p24 antigen in patients with AIDS and AIDS-related complex treated with zidovudine.

In an open study of the treatment of patients with AIDS-related complex (ARC) and AIDS with zidovudine, we evaluated the response of serum p24 antigen (p24Ag) and antibody to p24Ag (anti-p24) levels. Before treatment, serum from 49 out of 73 (67%) patients was p24Ag-positive, and of these patients 42 received zidovudine 800-1200 mg daily for greater than 4 weeks and had a baseline mean serum level of p24Ag of 119 pg/ml (s.e. 15.7). On zidovudine there was a reduction of p24Ag to 21.12% (s.e. 4.76) of pretreatment values at 3 months; however, there was a subsequent trend for levels after 6 months to increase to greater than 50% of pretreatment levels at 12 months. Serum levels of anti-p24 were measured in 26 patients. Of 16 patients whose serum contained p24Ag and 10 whose serum did not, four and nine, respectively, had detectable levels of anti-p24. There was no significant change in the serum anti-p24 with zidovudine therapy.

AIDS-Related Complex↗
PubMed1989

Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.

OBJECTIVE: To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN: Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING: Outpatient department of genitourinary medicine. PATIENTS: A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS: The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Prevalence of antibodies to human immunodeficiency virus, gonorrhoea rates, and changed sexual behaviour in homosexual men in London.

The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually-transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy.

Acquired Immunodeficiency Syndrome↗