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Biomedical subjects

M A French

Publications and source records attributed to M A French.

At least 55 records · Page 3Linked to original sources
PubMed1996

Declining incidence and later occurrence of Kaposi's sarcoma among persons with AIDS in Australia: the Australian AIDS cohort.

OBJECTIVE: To explore trends in cumulative incidence of Kaposi's sarcoma (KS) and the level of immunodeficiency at KS diagnosis among people with AIDS in Australia. SETTING: Three hospital-based HIV units. STUDY POPULATION: Retrospective cohort of 2580 people diagnosed with AIDS over the period 1983-1994, representing 45% of cases of AIDS in Australia over this period. METHODS: Data including date and CD4 T-lymphocyte count of KS diagnosis was abstracted from medical records. KS occurring as both an initial and subsequent AIDS illness was included. Three subcohorts were defined based on interval of AIDS diagnosis: 1983-1987, 1988-1990, 1991-1994. Cumulative risk estimates for KS development were calculated by the Kaplan-Meier method. RESULTS: KS was diagnosed in 716 people (27.8%), and in 451 (63%) of these as the initial AIDS illness. There was a decline over time in cumulative incidence of KS (P < 0.0005); the cumulative risk of KS at 1 year after AIDS diagnosis declined from 35% for those diagnosed with AIDS during 1983-1987 to 25% for 1991-1994. This decline was not due to a decline in homosexual HIV exposure category, and was independent of CD4 T-lymphocyte count at AIDS. In multivariate analysis independent risk factors for KS development were year of AIDS diagnosis (P = 0.003), male homosexuality (P = 0.003), and CD4 T-lymphocyte count at AIDS greater than 150 x 10(6)/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67 x 10(6)/l in 1984-1987 to 20 x 10(6)/l for 1991-1994 (P < 0.0005). CONCLUSION: The decline in incidence and later occurrence of KS suggest several hypotheses, including declining prevalence or reduced virulence of a KS cofactor.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cerebral mass lesions due to cytomegalovirus in patients with AIDS: report of two cases.

Cytomegalovirus (CMV) is an increasingly important opportunistic pathogen in patients with HIV infection and advanced immune deficiency. Neurological complications due to CMV cause significant morbidity but may be treatable with specific anti-viral therapy: cerebral mass lesions are not a generally recognised manifestation. We report two patients with CMV encephalitis presenting as a cerebral mass lesion, with simultaneous occurrence of a pleuro-pulmonary mass also caused by CMV in one case, and with concurrent polyradiculomyelopathy in the other. The spectrum of previously reported clinical and radiological features of CNS involvement in AIDS is discussed. CMV should be considered in the differential diagnosis of cerebral mass lesions in patients with HIV infection and severe immune deficiency so that anti-viral therapy can be rapidly deployed.

AIDS-Related Opportunistic Infections↗
PubMed1995

Increasing the dietary polyunsaturated fat content alters whole-body utilization of 16:0 and 10:0.

Six healthy adult males were fed four different diets to determine the effects of the quantity of fat (30% or 40% of energy as fat) and type of fat (polyunsaturated or saturated) on utilization of fatty acids. Each diet was fed for 15 d. The ratio of dietary polyunsaturated to saturated fat (P:S) was formulated at either 0.2 or 1.0 at both fat intakes. Subjects provided breath tests to measure background 13C and response to [1-13C]10:0 and [1-13C]16:0 fed with a test meal. Increasing the P:S increased whole-body oxidation of labeled 10:0 by 30% after consumption of both low- and high-fat diets. When labeled 16:0 was fed, the amount of 13C excreted in breath increased by a factor of 2.4 after the low-fat diet with a high P:S compared with the diet with a low P:S. The results suggest that the amount and type of fat in the diet affect utilization of individual fatty acids in normal subjects.

Adult↗
PubMed1995

Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4.

In order to define abnormalities of humoral immunity which determine susceptibility to respiratory tract infections in IgA-deficient adults, serum IgG subclass concentrations, and serum concentrations of pneumococcal antibodies and Haemophilus influenzae type B (Hib) antibodies sera from IgA-deficient adults with and without susceptibility to respiratory tract infections were compared. Infection susceptibility was not related to the degree of IgA deficiency, but was related to deficiency of IgG4 and, to a lesser extent, IgG2, as well as to low basal serum concentrations of pneumococcal polysaccharide antibodies. The combination of IgG2 and/or IgG4 deficiency and a non-protective basal serum concentration of antibody against two or more pneumococcal polysaccharides was present in the serum of six of 12 (50%) patients with severe infections, but only one of 44 (2%) patients without infections. Furthermore, the preservation of antibody responses against the most immunogenic pneumococcal polysaccharide type 3, but not against the less immunogenic types 7F, 9N and 14, in patients with severe infections suggested that abnormalities of pneumococcal polysaccharide antibody responses might include defects of affinity maturation.

Adolescent↗
PubMed1994

Detection of subclinical Mycobacterium avium intracellulare complex infection in immunodeficient HIV-infected patients treated with zidovudine.

OBJECTIVE: To test the hypothesis that subclinical Mycobacterium avium intracellulare complex (MAC) infection may result in the development of a tuberculin response in immunodeficient HIV-infected individuals treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: The Western Australian HIV Cohort Study; a prospective, single centre, population-based observational study of the natural history of HIV disease. PATIENTS: Forty-nine patients with impaired delayed-type hypersensitivity (DTH) responses and negative tuberculin responses in whom DTH responses were augmented within 6 months of starting zidovudine therapy. OUTCOME MEASURES: Progression to disseminated MAC infection stratified according to the presence or absence of a tuberculin response in the first 6 months of zidovudine therapy. RESULTS: Twenty-nine of the patients developed a post-zidovudine tuberculin response. None of the tuberculin non-responders developed disseminated MAC infection during the study period; the Kaplan-Meier probability estimate of disseminated MAC infection was 50% at 24 months and reached 100% 40 months after zidovudine was commenced in tuberculin responders. All patients with disseminated MAC infection had become anergic to all antigens, including tuberculin, before diagnosis. The probability of a post-zidovudine tuberculin response was related to the severity of peripheral blood CD4+ T-cell depletion, rising from an estimated 20% at 20% CD4+ T cells to 100% at < or = 1% CD4+ T cells. CONCLUSIONS: The restoration of a cellular immune response against subclinical MAC infection can be demonstrated by measuring the DTH response to tuberculin in patients with impaired DTH augmented by zidovudine therapy. The findings suggest that MAC infection is almost inevitable, but often asymptomatic, in profoundly immunodeficient HIV-infected patients and that a prolonged subclinical phase of MAC infection is usual.

AIDS-Related Opportunistic Infections↗
PubMed1994

Severity and outcome of Pneumocystis carinii pneumonia (PCP) in patients of known and unknown HIV status.

Of 170 Western Australian patients who had their first AIDS-defining illness between 1 January 1983 and 31 December 1991, 61 (36%) were of unknown HIV antibody status (AIDS presenters), while 109 (64%) were of known HIV antibody status (HIV presenters). Pneumocystis carinii pneumonia (PCP) was less common as the AIDS-defining illness in HIV presenters (41% versus 62%, p = 0.005). In this study of 70 patients with PCP as the index AIDS diagnosis, 36 were HIV presenters and 34 were AIDS presenters. Ten HIV presenters were taking prophylaxis at the time PCP manifested. The duration of symptoms of cough or dyspnea before the diagnosis of PCP was shorter, and the arterial PO2 measurement on admission was higher in those on prophylaxis, and a lower proportion of patients on prophylaxis required hospital admission (p < or = 0.05 for all comparisons). Furthermore, the CD4 counts at diagnosis of PCP were lower in patients taking PCP prophylaxis (mean 26 x 10(6)/L) than in patients who were not (mean 94 x 10(6)/L, p = 0.007). Of seven patients who died of PCP, none were receiving treatment for HIV disease before AIDS presentation. These findings suggest that PCP is prevented or deferred in patients receiving care for HIV disease and is less severe as a result of early diagnosis and treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1993

When do patients present with HIV infection?

A high proportion of people infected with HIV are not diagnosed until they have developed or are on the verge of developing AIDS. Ignorance of their risk of infection or fear of the implications of a diagnosis still play a part in their failure to have an HIV antibody test. Earlier diagnosis of HIV-induced disease is particularly important for this group, as is continuing education about the risks of infection and the value of early diagnosis.

AIDS Serodiagnosis↗
PubMed1993

Polymorphic MHC ancestral haplotypes affect the activity of tumour necrosis factor-alpha.

It remains unclear which MHC loci are involved in susceptibility to autoimmune diseases and immune deficiencies. We have chosen to evaluate whether different alleles of tumour necrosis factor-alpha (TNF-alpha) are important, as TNF has been implicated in the etiology of many immunological disorders. We have shown previously that a restriction fragment length polymorphism in the TNF region correlates with MHC ancestral haplotypes. We therefore examined the effect of ancestral haplotype on the activity of TNF-alpha in culture supernatants of lymphoblastoid cell lines. The results demonstrate that TNF-alpha activity in supernatants of 8.1 (A1, B8, DR3) cell lines was higher than that present in the supernatants from cells homozygous for eight different MHC ancestral haplotypes, and indicate that polymorphisms in TNF-alpha, or in other MHC genes that regulate TNF, may be responsible for the 8.1 phenotype.

Cell Line, Transformed↗
PubMed1993

Clinical immunology and HIV infection.

Clinical immunologists play a major role in the multidisciplinary approach to the management of human immunodeficiency virus (HIV) infection and its complications in Australia, through involvement with the clinical and laboratory management of patients as well as with research on disease pathogenic mechanisms. Consequently, immunological monitoring of the pathogenic effects of chronic HIV infection is commonplace, allowing for studies on the clinical utility of immunological investigations as a means of monitoring the severity of HIV-induced immunopathology and immunodeficiency to be undertaken. Such studies have demonstrated the clinical utility of CD4+ T-cell assays, but studies on cutaneous delayed-type hypersensitivity have demonstrated that the cellular immunodeficiency induced by chronic HIV infection may be more complex than CD4+ T-cell depletion alone. In addition, the involvement of clinical immunologists has greatly facilitated studies on the pathogenic mechanisms underlying HIV-induced immunopathology. Such activities place Australia in a very advantageous position for future studies on the use of immune-based therapies for controlling the pathogenic effects of chronic HIV infection.

HIV Infections↗
PubMed1992

Exposure to blood borne infections in health care workers.

OBJECTIVE: To determine the incidence and nature of occupational exposures to blood and body fluids in health care workers. DESIGN: 332 reports of occupational exposure were analysed and are presented. SETTING: A major teaching hospital. PARTICIPANTS: All staff at Royal Perth Hospital who reported an occupational exposure to blood or body fluids to the Department of Clinical Immunology between 1 January 1990 and 31 August 1991. OUTCOME MEASURES: The rate of reported occupational exposure according to staff category, nature of exposure, HIV status of source patient, activity at the time of exposure and compliance with infection control measures. RESULTS: 332 reports from 323 health care workers were received, giving an overall incidence of 6.1 per 100 full time equivalent (FTE) years. Nursing staff (9.4/100 FTE years) and medical staff (9.0/100 FTE years) reported exposure more frequently than housekeeping staff (2.5/100 FTE years) or paramedical staff (2.3/100 FTE years) (P < 0.001). The rate of exposure to HIV antibody positive patients was only 0.24/100 FTE years. Needlestick or other blood contaminated sharps injuries accounted for 83.4% (277/332) of reports and failure to observe universal precautions for 34.0% of reports. Insertion and operation of parenteral lines (24%) and performing operations (15.4%) were the activities most often associated with occupational exposure. No occupationally acquired infections were observed. Despite the immediate availability of zidovudine, acceptance by health care workers with high risk occupational exposure was low (18.8%). CONCLUSIONS: Occupational exposure to blood and body fluids is common among health care workers but most exposures confer a low risk of blood borne infection. The introduction of an occupational exposure assessment program has many benefits, including optimal management of injuries and acquisition of data on infection control measures, and may protect health care institutions from false claims for compensation.

Blood↗
PubMed1992

Epidemiology of late presentation of HIV infection in Western Australia.

OBJECTIVE: To determine the incidence of and reasons for late presentation of patients infected with the human immunodeficiency virus (HIV), and the demographic characteristics of these late presenters, who first seek medical attention when they have an illness that defines the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective analysis of clinical and demographic data relating to 106 sequential AIDS diagnoses in Western Australia. Surviving patients were questioned during routine medical and social work interviews to identify the reasons for late presentation. SETTING: Royal Perth Hospital, the sole specialist referral centre for the management of infection with the human immunodeficiency virus (HIV) in Western Australia. PARTICIPANTS: All patients presenting or referred to Royal Perth Hospital with an AIDS-defining condition between 1 January 1988 and 1 July 1991. RESULTS: Forty-one of 106 (39%) patients presenting with an AIDS-defining condition had known of their HIV status for eight weeks or less (late presenters). The proportion of late presenters decreased from 61% in 1988 to 34% in 1989 (P less than 0.05). Six of the 41 late presenters died during their initial admission compared with only one of the 65 early presenters (P less than 0.02). Sixty-six per cent of late presenters compared with only 35% of early presenters had pneumocystis pneumonia as their AIDS-defining condition (P less than 0.01). There was no significant difference in age at diagnosis of AIDS, martial status, sex or risk factors between the early and late presentation groups. Reasons given for late presentation included lack of knowledge of advances in the treatment of HIV infection, concerns about confidentiality and beliefs that sexual behaviour had been relatively "safe" from risk of HIV infection. CONCLUSIONS: While the proportion of patients presenting late is decreasing, late presentation continues to be a problem. Reasons for delayed presentation are not entirely clear, but can be explained in terms of psychosocial and physiological influences. How and to what degree each of these contribute to timing of presentation is yet to be determined.

AIDS Serodiagnosis↗
PubMed1992

Zidovudine-induced restoration of cell-mediated immunity to mycobacteria in immunodeficient HIV-infected patients.

OBJECTIVE: To describe a localized form of Mycobacterium avium intracellulare (MAI) infection occurring concurrently with the restoration of cutaneous delayed-type hypersensitivity (DTH) responses to mycobacterial antigens after commencement of zidovudine therapy in immunodeficient HIV-infected patients. PATIENTS: The first 108 Western Australian patients with a CD4+ T-cell count of < 200 x 10(6)/l and/or symptomatic disease to be given zidovudine (ZDV), of whom 72 had adequate DTH data. METHODS: DTH responses to seven antigens were measured by the 'Multitest' method before and on at least two occasions during the 6 months after commencing ZDV. All patients were reviewed at regular intervals and clinical events recorded. RESULTS: Of the 64 patients who were anergic to tuberculin before commencing ZDV, 27 (42%) developed a DTH response to tuberculin after ZDV. Four of the nine patients with a 'Multitest' tuberculin response of > or = 8 mm and one patient who developed a positive Mantoux test to M. avium purified protein derivative developed an illness characterized by localized MAI infection, lymphadenopathy and/or severe fevers after 1-2 weeks. CONCLUSIONS: The development of localized MAI infection and/or fevers shortly after commencing ZDV in immunodeficient HIV-infected patients may reflect restoration of cellular immunity to mycobacterial antigens in some patients rather than early failure of therapy or hypersensitivity to ZDV.

AIDS-Related Opportunistic Infections↗
PubMed1991

Pyomyositis complicating the acquired immunodeficiency syndrome. A report of two cases with coexistent neutropenia.

OBJECTIVE: To identify some factors contributing to the development of pyomyositis in patients with the acquired immunodeficiency syndrome (AIDS) by a report of two cases and a review of the literature. CLINICAL FEATURES: A 36-year-old man with AIDS presented with tenderness of the left adductor longus muscle; a 28-year-old man with AIDS presented with fever and left leg pain. Both men had a history of severe neutropenia induced by drug treatment and opportunistic infections requiring treatment in hospital. The pyomyositis was defined by a gallium-67 scan (and, in one case, by a computed tomography scan). In one case Staphylococcus aureus was cultured from blood; in the other it was cultured from pus from the pyomyositic abscess. INTERVENTIONS: Both patients had their abscesses drained. The first patient was treated with flucloxacillin (2 g every four hours, given intravenously) and rifampicin (450 mg by mouth each day). The second patient was treated with flucloxacillin (2 g every four hours, given intravenously) and ticarcillin (3 g every six hours, given intravenously). OUTCOME: After their symptoms abated, both patients were discharged from hospital, taking flucloxacillin by mouth as ongoing treatment. CONCLUSIONS: Staphylococcal infections are increasingly common in neutropenic patients. Neutropenia is likely to have contributed to the development of pyomyositis in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Normal unstimulated lymphocytes produce granulopoietic inhibitory activity.

Normal unstimulated lymphocytes cocultured with normal bone marrow will inhibit day-7 colony- forming units in culture. We have shown that this phenomenon has a molecular basis and attempted to characterize it further. Using specific assays and neutralizing monoclonal antibodies we have found that this granulopoietic inhibitory activity (GIA) is not due to alpha- or gamma-interferon, tumor necrosis factor, or acidic or basic isoferritins. Biochemical studies suggest that it is a glycoprotein with a molecular weight greater than 100,000 daltons. It appears to act on cells in S phase, although it may not be S-phase specific. GIA represents a novel inhibitor that merits further investigation.

Bone Marrow↗
PubMed1990

Correction of human immunodeficiency virus-associated depression of delayed-type hypersensitivity (DTH) after zidovudine therapy: DTH, CD4+ T-cell numbers, and epidermal Langerhans cell density are independent variables.

Twenty-four patients with various degrees of human immunodeficiency virus (HIV)-associated immunodeficiency were treated with zidovudine for up to 6 months. Nineteen of these patients had persistent depression of delayed-type hypersensitivity (DTH) responses prior to commencing therapy. In 11 of these 19 patients (58%) there was sustained improvement of DTH responses with the maximal effect occurring at approximately 3 months after therapy was started. DTH declined after 3 months but remained significantly higher than baseline at 6 months. Patients who did not have a sustained increase in DTH responses had more severe disease than those that did. Blood CD4+ T-cell counts increased in the majority of patients on zidovudine therapy, but varied independently of DTH responses. Epidermal Langerhans cell density was lower in HIV-infected patients than controls but also varied independently of DTH responses before and after zidovudine therapy. We suggest that sequential measurement of DTH responses is a valuable means of monitoring the restoration of cell-mediated immune responses by zidovudine in some HIV-infected patients. Our findings also demonstrate the need to define the processes involved in the restoration of DTH responses as this may lead to new approaches to the therapeutic manipulation of cell-mediated immune responses in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗