Reducing the vertical transmission of HIV. Screening programme has not failed.
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Female↗
Biomedical subjects
M Johnson
Publications and source records attributed to M Johnson.
Enhanced liver cell mutations in trematode-infected Big Blue transgenic mice.
Parasite infections in humans have long been associated with specific types of cancers. Schistosoma hematobium is a known inducer of urinary bladder cancer, Helicobacter pylori is a gastric carcinogen, and hepatitis B virus and Opisthorchis viverrini are causative agents of liver cell cancers. Another liver fluke, Fasciola hepatica, has also been identified as a neoplastic risk agent, primarily in animals. We used F. hepatica as a model agent to determine if the presence of an aggressive liver fluke could induce mutagenic events in mammalian tissue. Using the Big Blue(R) transgenic mouse assay, we found a two-fold increase in lacI mutations in cells harvested from mice harboring F. hepatica worms when compared to uninfected control animals. These data indicate that biological infections can cause increased genetic damage in surrounding host tissue.
Animals↗
Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.
To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.
AIDS-Related Opportunistic Infections↗
Rhodopsin-family receptors associate with small G proteins to activate phospholipase D.
G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA. Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins. These receptors contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxy-tryptamine reduced its sensitivity to the inhibitor. Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.
ADP-Ribosylation Factors↗
Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.
BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.
AIDS-Related Opportunistic Infections↗
Interferon-induced protein 10 and interleukin 8. C-X-C chemokines present in proliferative diabetic retinopathy.
OBJECTIVE: To determine vitreous levels of interleukin 8 (IL-8) and interferon-induced protein 10 (IP-10), which are members of the C-X-C chemokine family that promote and inhibit neovascularization, respectively. METHODS: We measured the levels of IL-8 and IP-10 by specific enzyme-linked immunosorbent assays in the vitreous from 30 patients with proliferative diabetic retinopathy (PDR) and 10 control patients undergoing vitrectomy for idiopathic macular holes or idiopathic macular puckers. RESULTS: Detectable levels of IL-8 were found in 23 of 24 patients with active PDR, 4 of 6 patients with inactive PDR, and 6 of 10 controls. Levels of IL-8 were significantly increased in vitreous samples from the patients with active PDR (P = .02) when compared with vitreous samples from the controls. The IL-8 levels detected in vitreous samples from patients with inactive PDR were not significantly elevated over those found in the control samples. Interferon-induced protein 10 was detected in the vitreous samples from 23 of 24 patients with active PDR, all patients with inactive PDR, and 9 of 10 controls. Significant elevations of IP-10 were measured in samples from patients with active PDR (P = .004) and in those with inactive PDR (P = .00) over those from controls. In addition, levels of IP-10 were significantly elevated in vitreous samples from patients with inactive PDR compared with vitreous samples from patients with active PDR (P = .02). CONCLUSION: Both IL-8 and IP-10 participate in the pathogenesis of PDR.
Adult↗
Testing for HIV antibodies should be offered on a same-day basis.
We review our experience of testing over 22 000 patients who requested HIV antibody results on a same-day basis. We find that such a service can be provided without compromising the quality of laboratory work or increasing the cost per test. This service is popular with patients, who appear to contain high risk individuals because 2.8 were shown to be HIV-positive. By reducing bureaucratic hurdles, same-day testing clinics may encourage people to come forward for HIV testing and provide a means of offering chemotherapy (directed either at HIV itself or at opportunistic infections) without delay. We thus argue for the proposition.Copyright 1998 John Wiley & Sons, Ltd.
Journal Article↗
Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes.
Our purpose is to assess whether genotypes of the vitamin D receptor (VDR) and estrogen receptor (ER) and their interaction influence changes in bone mass in postmenopausal Caucasian women with and without hormone replacement therapy (HRT). A population of 108 US Mid-West women who participated in a study of low-dose continuous estrogen/progestin was genotyped at the VDR BsmI site and the ER XbaI and PvuII sites. Adequate vitamin D and calcium nutritional intakes were assured in all the study subjects. For the 3.5-year duration of the study, we analyzed changes in bone mineral density (BMD) at the spine, femoral neck, distal radius, and the total body (total body bone mineral content, tbBMC). We adjusted for confounding factors, such as age and weight, in the analysis. We found that VDR and/or ER genotypes and/or their interaction generally had significant effects on the changes in the bone mass measurements in both the placebo and HRT groups. When a significant gene-by-gene interaction exists between VDR and ER genotypes, failure to account for them in analyses may yield nonsignificant results, even if significant genotypic effects exist. The amount of variation in changes in bone mass measurements explained by the total genotypic effects of the VDR and ER loci varies from approximately 1.0% (for the tbBMC changes in combined placebo and HRT groups) to approximately 18.7% (for the spine BMD changes in the HRT group). These results suggest that individual genotypes are important factors in determining changes in bone mass in the elderly with and without HRT and thus may need to be considered with respect to the treatment to preserve bone mass in elderly Caucasian women.
Aged↗
Clinical neurochemistry: developments in dementia research based on brain bank material.
Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.
Brain↗
Fowl adenovirus recombinant expressing VP2 of infectious bursal disease virus induces protective immunity against bursal disease.
The right hand end Nde I fragment 3 (90.8-100 map units) of the fowl adenovirus serotype 10 (FAV-10) was characterised so as to allow the location of an insertion site for recombinant vector construction. Infectious bursal disease virus (IBDV) VP2 gene from the Australian classical strain 002/73, under the control of the FAV-10 major late promoter/leader sequence (MLP/LS) was inserted into a unique Not I site that was generated at 99.5 map units. This recombinant virus was produced without deletion of any portion of the FAV-10 genome. When administered to specific pathogen free (SPF) chickens intravenously, intraperitoneally, subcutaneously or intramuscularly, it was shown that the FAV-10/VP2 recombinant induced a serum VP2 antibody response and protected chickens against challenge with IBDV V877, an intermediate virulent classical strain. Birds were not protected when the recombinant was delivered via the conjunctival sac.
Animals↗
First International Reference Preparation for Individual Proteins in Urine. IFCC Working Group on Urine Proteins. International Federation of Clinical Chemistry.
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Clinical Laboratory Techniques↗
The nature of fatigue in multiple sclerosis.
The aim of this cross-sectional descriptive study was to determine whether people with multiple sclerosis differentially experience physical and mental fatigue, and whether the pattern of fatigue is influenced by mood, disease duration, or disease course. Seventy-eight consecutive out-patients with multiple sclerosis were asked to complete the Fatigue Rating Scale (FRS) and the Hospital Anxiety and Depression Scale (HAD). Sixty-eight (87%) subjects completed the questionnaires. Fifty-eight (85%) subjects in this group scored above the recommended cut-off for fatigue on the FRS scale. Both the mental fatigue score and the total fatigue score were positively correlated with the depression and anxiety scores on the HAD scale. There was no significant correlation between the physical fatigue score and either of the HAD subscale scores. There was no significant association between duration of disease or disease course and the total scores or subscale scores of the FRS and HAD. This is the first reported study to differentiate between mental and physical fatigue in multiple sclerosis and to demonstrate a significant correlation between fatigue and mood level. This has important implications for the effective treatment of fatigue in multiple sclerosis.
Adult↗
Expanding the clinicopathologic spectrum of herpes simplex encephalitis.
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Adult↗
Development of fluticasone propionate and comparison with other inhaled corticosteroids.
Fluticasone propionate (FP) is a trifluorinated glucocorticoid based on the androstane nucleus. It was selected for development from structure-activity relationships (topical anti-inflammatory, cutaneous vasoconstriction, and hypothalamic-pituitary-adrenal axis suppression) of a series of 17beta-carbothioates. FP is 3-, 300-, and 1000-fold more lipophilic than beclomethasone dipropionate, budesonide, and triamcinolone acetonide, respectively. FP has an absolute affinity (KD) for the glucocorticoid receptor of 0.5 nmol/L and a relative receptor affinity 1.5-fold higher than beclomethasone-17-monopropionate (17-BMP) and mometasone furoate, 3-fold higher than budesonide, and 20-fold higher than flunisolide and triamcinolone acetonide. The rate of association of FP with the receptor is faster and the rate of dissociation slower than other corticosteroids. The resulting half-life of the FP active steroid-receptor complex is >10 hours, compared with approximately 5, 7.5, and 4 hours for budesonide, 17-BMP, and triamcinolone acetonide, respectively. FP has high selectivity for the glucocorticoid receptor, with little or no activity at other steroid receptors. FP is more potent than beclomethasone dipropionate, budesonide, triamcinolone acetonide, and mometasone furoate in inhibiting human T-cell migration and proliferation, inhibiting CD4+ T-cell cytokine and basophil histamine release, attenuating adhesion molecule expression, stimulating inflammatory cell apoptosis, and inducing cellular antiprotease release. In asthma patients, FP decreases the number of CD3+, CD4+, CD8+, and CD25+ T cells, mast cells, and eosinophils in bronchial biopsies, in addition to suppressing CD1a-dendritic and IgE+ cells and HLA-DR. FP, therefore, has a good pharmacologic profile for a topical steroid with increased intrinsic glucocorticoid potency and potent anti-inflammatory activity.
Administration, Inhalation↗
Telemedicine diagnosis of eye disorders by direct ophthalmoscopy. A pilot study.
OBJECTIVE: To report a pilot study of telemedical direct ophthalmoscopy in the diagnosis of acquired immune deficiency syndrome (AIDS)-related retinopathy in a human immunodeficiency virus (HIV)-positive population and in the diagnosis of glaucoma, cataract, and retinopathy in a diabetic population. DESIGN: Prospective comparative case series. PARTICIPANTS: Seventeen HIV-positive and 20 diabetic patients. METHODS: A direct ophthalmoscope custom-fitted with a digital microcamera capable of transmitting images from any of 61 sites within the Georgia Statewide Telemedicine Program was used by a nonophthalmologist to examine 34 eyes of 17 HIV-positive patients and 39 eyes of 20 patients with diabetes. Fundus images were transmitted in real-time to a reviewing ophthalmologist. An in-person, comprehensive examination including indirect ophthalmoscopy, was performed by a second ophthalmologist. Telemedical examination was compared to the in-person comprehensive examination. RESULTS: For the HIV study, 21 eyes did not show HIV retinopathy (noninfectious retinopathy with cotton-wool spots) by in-person examination. Telemedical examination correctly identified 20 of these eyes as disease-free (specificity = 95%). HIV retinopathy was present in 12 of the 34 eyes by in-person evaluation with telemedical examination correctly diagnosing 10 of these eyes (sensitivity = 83%). One eye with dense cataract and retinal detachment was unable to be evaluated ophthalmoscopically by either in-person or telemedical examination. Telemedical and in-person assessments for HIV retinopathy were identical in 100% of eyes without cataract. Disagreement in diagnosis between telemedical and in-person examination was associated with cataract (P < 0.0007). For the diabetes study, because of an inadequate image, telemedical examination was unable to classify 46% and 36% of eyes for glaucoma and diabetic retinopathy, respectively. Inability to make a telemedical determination for glaucoma (P < 0.011), nonproliferative (P < 0.064) and proliferative (P < 0.064) diabetic retinopathy was associated with cataract. Of the eyes that were able to be assessed by telemedical examination for diabetic retinopathy (n = 25), glaucoma (n = 21), and cataract (n = 39), the accuracy was poor (sensitivity = 29%, 50%, and 41%, respectively). Telemedical examination for diabetic retinopathy and glaucoma was more likely to agree with in-person examination in eyes without cataract as compared to eyes with cataract (not statistically significant). CONCLUSION: Telemedical direct ophthalmoscopic, real-time fundus imaging may provide a valuable means for providing ophthalmic consultation to the primary care physician in younger patients without lens or media opacity, but is inadequate for eyes with any degree of lens or media opacity.
Acquired Immunodeficiency Syndrome↗
Development of a syncytia inhibition assay for the detection of antibodies to bovine leukemia virus in naturally infected cattle; comparison with Western blot and agar gel immunodiffusion.
A syncytia inhibition assay (SIA) for the detection of antibodies to bovine leukemia virus is described. This test involves specific antibody-mediated inhibition of BLV-induced cytopathic effects in an indicator cell line. A total of 300 sera were screened commercially by agar gel immunodiffusion (AGID) and were then screened by Western blot and SIA. The new assay system provided results which were comparable to Western blot and AGID. The results obtained suggest that SIA may be more sensitive than either of the other two assay systems examined for the determination of the infection status of cattle.
Animals↗
Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.
BACKGROUND/AIMS: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. METHODS: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. RESULTS: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). CONCLUSIONS: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.
Adult↗
The Quality Assurance Agency for higher education (England) nursing subject review.
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Accreditation↗