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D J Jeffries

Publications and source records attributed to D J Jeffries.

At least 55 records · Page 3Linked to original sources
PubMed1990

Synthesis and anti-HIV evaluation of some phosphoramidate derivatives of AZT: studies on the effect of chain elongation on biological activity.

A series of phosphoramidate derivatives of the anti-HIV drug AZT has been prepared as membrane soluble pro-drugs of the bio-active nucleotide forms and evaluated in vitro against HIV-1. Terminal substituted alkyl amines have a pronounced anti-HIV effect: this effect declines upon increasing the length of the methylene spacer. The results are consistent with a mechanism of action involving intracellular cleavage of the phosphoramidate bond, and release of the nucleotide, or a derivative thereof. Full spectroscopic data are included on the products and their phosphorochloridate precursors.

Cells, Cultured↗
PubMed1990

Detection of HIV-1 in human lung macrophages using the polymerase chain reaction.

We have used the polymerase chain reaction to investigate HIV-1 infection of lung macrophages from 44 AIDS patients with pneumonia. Proviral HIV-1 DNA was detected in the lung macrophages of 47% (21 of 44) of patients tested; 32% (seven of 21) of the patients had Pneumocystis carinii pneumonia (PCP), and 56% (11 of 21) had pneumonia caused by other aetiological agents. Matched peripheral blood specimens were obtained from 22 patients in this study, and HIV-1-specific DNA was detected in 100% (22 out of 22) of non-adherent white cell preparations tested. HIV was detected in blood monocytes of 11 out of 22 patients (50%), and a virus signal was also found in the lung macrophages of eight of these patients. Our results indicate that PCP does not predispose lung macrophages to HIV-1, nor does HIV-1 infection of lung macrophages increase the probability of contracting PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Elimination of high titre HIV from fibreoptic endoscopes.

Concern about contamination of fibreoptic endoscopes with human immunodeficiency virus (HIV) has generated a variety of disruptive and possibly unnecessary infection control practices in endoscopy units. Current recommendations on the cleaning and disinfection of endoscopes have been formulated without applied experimental evidence of the effective removal of HIV from endoscopes. To study the kinetics of elimination of HIV from endoscope surfaces, we artificially contaminated the suction-biopsy channels of five Olympus GIF XQ20 endoscopes with high titre HIV in serum. The air and water channels of two instruments were similarly contaminated. Contamination was measured by irrigating channels with viral culture medium and collecting 3 ml at the distal end for antigen immunoassay. Endoscopes were then cleaned manually in neutral detergent according to the manufacturer's recommendations and disinfected in 2% alkaline glutaraldehyde (Cidex, Surgikos) for two, four, and ten minutes. Contamination with HIV antigens was measured before and after cleaning and after each period of disinfection. Initial contamination comprised 4.8 x 10(4) to 3.5 x 10(6) pg HIV antigen/ml. Cleaning in detergent achieved a reduction to 165 pg/ml (99.93%) on one endoscope and to undetectable levels (100%) on four. After two minutes in alkaline glutaraldehyde all samples were negative and remained negative after the longer disinfection times. Air and water channels, where contaminated, were tested after 10 minutes' disinfection and were negative. These findings underline the importance of cleaning in removing HIV from endoscope and indicate that the use of dedicated equipment and long disinfection times are unnecessary.

Acquired Immunodeficiency Syndrome↗
PubMed1990

An update on HIV-testing at a London sexually transmitted diseases clinic: long-term impact of the AIDS media campaigns.

Trends in the number of tests for HIV-1 antibody at a London sexually transmitted diseases clinic showed substantial changes between September 1985 and June 1988. From an average of 100 tests per month between September 1985 and August 1986, the average increased to 365 tests per month for September 1986 to August 1987. This levelled off at 243 tests per month between September 1987 and June 1988. The average number of positive tests per month between September 1985 and June 1988 remained constant, though the number of seropositive tests in females increased. Male and female populations displayed similar temporal patterns. The greatest increase was seen in the tests generated by heterosexual males and females with no other risk factors. This group generated 42% of the 8012 tests performed during the study period. The Clinic's catchment area predominantly included London and surrounding areas and temporal patterns were similar for residents from each of the Thames Regions. The temporal patterns observed coincided with periods of increased media attention on HIV infection/AIDS and involved campaigns by the popular press, television, Department of Health Education Authority. The increase in tests during the time of maximum media exposure, the subsequent plateau at a level substantially higher compared with the period preceding the media campaigns and the large increase in heterosexual males and females tested, all suggest that the campaigns have contributed to increasing awareness of HIV infection/AIDS as a major contemporary public health problem.

AIDS Serodiagnosis↗
PubMed1989

Contamination of endoscopes used in AIDS patients.

Contamination of twenty endoscopes used in patients with AIDS was assessed. The suction-biopsy, air, and water channels and the insertion tube were sampled after use, after washing in detergent, and after disinfection for 2 min in 2% alkaline glutaraldehyde. The polymerase chain reaction with Southern blotting, cell cultures, and antigen immunoassay were used to detect human immunodeficiency virus (HIV). Samples were also examined for cytomegalovirus, adenoviruses, enteroviruses, herpes simplex virus, myxoviruses, hepatitis B surface antigen, fungi, and bacteria. Seven of twenty unwashed endoscopes were contaminated by HIV. Commensal bacteria were found in all endoscopes, Candida albicans in six, Staphylococcus aureus in five, and Pseudomonas aeruginosa in five. Washing alone removed all detectable organisms from 66 of 68 contaminated sites; Neisseria spp were recovered from two air channels after washing but not after disinfection. Washing achieved a mean reduction of 4.93 (95% confidence interval 3.69-6.17) colony forming units per ml.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Chemical inactivation of HIV on surfaces.

To assess whether alcohol and glutaraldehyde are effective disinfectants against dried HIV the virucidal effects of 70% alcohol (ethanol and industrial methylated spirit) and 1% and 2% alkaline glutaraldehyde were tested against cell associated and cell free HIV dried on to a surface. Virus stock (100 microliters) or 10,000 cultured C8166 T lymphocytes infected with HIV were dried onto sterile coverslips and immersed in 2% and 1% alkaline glutaraldehyde and 70% ethanol for 30 seconds and one, two, four, and 10 minutes, there being an additional time point of 20 minutes for cell free virus disinfected with 70% industrial methylated spirit. In addition, virus stock in neat serum was tested with 1% and 2% alkaline glutaraldehyde to see whether the fixative properties of glutaraldehyde impair its virucidal properties. Virus activity after disinfection was tested by incubating the coverslips (cell associated virus) or the coverslips and sonicated cell free virus with C8166 T lymphocytes. The lymphocytes were examined for the formation of syncytia and HIV antigens were assayed in the culture fluid. Both 2% and 1% alkaline glutaraldehyde inactivated cell free HIV within one minute; 2% alkaline glutaraldehyde also inactivated cell free virus in serum within two minutes, but a 1% solution was ineffective after 15 minutes' immersion. Cell associated HIV was inactivated by 2% alkaline glutaraldehyde within two minutes. Seventy per cent industrial methylated spirit failed to inactivate cell free and cell associated HIV within 20 and 15 minutes, respectively, and 70% ethanol did not inactivate cell free virus within 10 minutes. Seventy per cent industrial methylated spirit and ethanol are not suitable for surface disinfection of HIV. Fresh 2% solutions of alkaline glutaraldehyde are effective, but care should be taken that they are not too dilute or have not become stale when used for disinfecting HIV associated with organic matter.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Targets for antiviral therapy of human immunodeficiency virus infection.

The development of potent anti-retroviral drugs is central to the control of human immunodeficiency virus (HIV) infection and the prevention of disease. Despite the benefit (albeit limited) shown by the early trials of zidovudine in patients with acquired immune deficiency syndrome (AIDS), there is general agreement that the best prospects for therapeutic intervention lie in the use of agents early in the infectious process. There is a definite possibility that this can be achieved if compounds acting specifically against virus encoded events can be found or developed. Although relatively simple in its structure, HIV is highly sophisticated in its mode of replication. The unique nature of the replication cycle of the retroviridae and the specific controlling mechanisms operative in HIV offer a number of possible targets for chemotherapeutic agents. The details of the structure and replication cycle of HIV will be briefly reviewed with comments on the possible virus specific and non-specific sites for potential antiviral drug development. The first specific target to be recognised was the unique, virus-associated enzyme, the reverse transcriptase (RNA directed DNA polymerase). Several inhibitors of reverse transcriptase were identified during the 1970s (e.g. suramin, HPA23, phosphonoformate). These have been found, in early trials, to be either insufficiently potent or too toxic to consider for development as anti-retroviral drugs. Indeed, knowledge of the pathogenesis of HIV infection led to the realisation that any putative drug would need to satisfy several important criteria; namely potency, low toxicity, easy administration, penetration of the blood-brain barrier and hopefully, low production costs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Clinical experience with zidovudine for patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

AIDS-Related Complex↗
PubMed1989

The antiviral activity of dideoxycytidine.

2',3'-Dideoxycytidine (ddc) is a 2',3'-dideoxypyrimidine nucleotide which has been shown to be active against human immunodeficiency virus type 1 (HIV-1) in cell cultures. This article reviews some of the laboratory studies with this antiviral compound, and available pharmacokinetic and toxicity data from phase 1 studies of ddc alone and in alternation with zidovudine in patients with AIDS and ARC. Though ddc has potent activity against HIV-1 in vitro, serious toxic effects seen in phase 1 studies warrant continuation of trials to explore lower dosage regimens, alternation with zidovudine and intermittent therapy.

Animals↗
PubMed1989

The spectrum of cytomegalovirus infection and its management.

Serious disease due to cytomegalovirus (CMV) is almost totally confined to congenitally infected infants and the immunocompromised. Cell-mediated immunity is primarily responsible for the control of infection following primary infection and for prevention of disease after reactivation. In patients receiving active immunosuppression for transplantation, the choice of drug regimens is important in determining the likelihood of disseminated CMV infection and disease and it may be possible to control the infection by reducing the doses used. A number of strategies have been introduced in attempts to reduce the morbidity and mortality of CMV in the immunocompromised. These include prophylactic administration of specific immunoglobulin or acyclovir and the therapeutic use of several antiviral agents shown to have activity against CMV in vitro. Ganciclovir (DHPG) and foscarnet (phosphonoformate) have shown the most promise in clinical trials and ganciclovir has now been licensed for use in the UK, in sight- and life-threatening infections.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Ganciclovir therapy in iatrogenically immunosuppressed patients with cytomegalovirus disease.

A study of ganciclovir used on compassionate grounds in the treatment of severe cytomegalovirus disease in iatrogenically immunosuppressed and AIDS patients in Europe, commenced in June 1985. The results of 120 iatrogenically immunosuppressed patients treated between May 1986 and February 1988 are reported. Patients presented with systemic infection (58), pneumonia (58), retinitis (9) and infection of other organs (9). There was a favourable clinical response (as rated by the local physician) in 40 of 57 (70%) evaluable patients with systemic infection, 38/58 (65%) with pneumonia, 6/8 (75%) with retinitis, and 4/9 (44%) of those with CMV infection of other organs. Of particular note was the relatively high rate of short term survival (up to 12 days post therapy) in bone marrow transplant patients with CMV pneumonia, 10/19 (52%), compared to the 10% survival reported by Shepp et al., (1985). Adverse events were frequent (26%) and haematological effects necessitated discontinuation of treatment in 13/120 (11%) patients. The use of ganciclovir should be confined, therefore, to the treatment of severe cytomegalovirus disease.

Acyclovir↗
PubMed1989

Comparison of antigen capture assays against HIV-1 in evaluating antiviral compounds.

Five antigen capture enzyme-linked immunosorbent assays (ELISAs) have been assessed for detecting HIV-1 in tissue culture supernatants of cell cultures used routinely to investigate antiviral activity. Although all the ELISAs are very sensitive to low levels of antigens they have different characteristics when used for titrating virus antigens.

Enzyme-Linked Immunosorbent Assay↗
PubMed1989

Risk factors for HIV-1 infection in a British population: lessons from a London sexually transmitted diseases clinic.

Between September 1985 and June 1988, 6923 people (4550 men and 2373 women) were tested for HIV-1 antibodies at a sexually transmitted disease clinic, London, UK. Of the 6923 individuals tested, 558 (8%) were seropositive, of whom 523 (94%) were men and 35 (6%) women. Of the seropositives, 84% were homosexual or bisexual men, 5% were intravenous drug users, 4% were heterosexual contacts of HIV seropositives, 4% had multiple risk factors, 2% were heterosexual contacts of central African partners and 1% were heterosexuals with no other risk factors. This prevalence pattern conforms to that observed in other industrialized nations. For the women, heterosexual intercourse with an HIV-infected partner, intravenous drug use and heterosexual contact with a partner from central Africa were the main risk factors for infection. The important risk factors among the men were heterosexual contact with an HIV-seropositive partner, being homosexual or bisexual, intravenous drug use and heterosexual contact with a resident from central Africa. heterosexual and homosexual transmission were implicated as the main routes for viral spread in this British population.

Acquired Immunodeficiency Syndrome↗