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Biomedical subjects

M A French

Publications and source records attributed to M A French.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Central MHC genes, IgA deficiency and autoimmune disease.

IgA deficiency is a common immunological disorder that is sometimes associated with an immunodeficiency syndrome, allergic disease, autoimmune disease and gluten enteropathy. Many subjects with this deficiency, however, are healthy, at least for many decades. Analysis of the immunological and genetic abnormalities found in IgA deficiency and in some of the associated disorders has led to the postulate that a genetically determined defect of immunoregulation underlies all of these diseases. Here, Martyn French and Roger Dawkins propose that the products of genes located within the central region of the major histocompatibility complex (MHC) regulate B cells and/or antibody production. Particular MHC ancestral haplotypes contain specific alleles and arrangements of these genes, thereby explaining associations with either increased or decreased production of immunoglobulin isotypes by B cells.

Agammaglobulinemia

Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations.

Several alleles at multiple HLA loci have been found to be associated with infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4; DR1, DR3 and DQ1, are associated with particular disease manifestations and/or disease progression. Furthermore, in a pilot study we have shown an increase in the frequency of C4 null alleles and suggested that all the reported HLA alleles could reflect association with a limited number of ancestral haplotypes (AHs). On this occasion, we studied 122 Caucasoid patients classified according to Centers for Disease Control (CDC) criteria. The control group consisted of 67 seronegative homosexual or bisexual males at risk of developing HIV infection. C4 null alleles were unequivocally present in 58% of patients in CDC IV compared with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05). Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and IV, respectively, but in 30% of the seronegative subjects. An increased frequency of three AHs largely accounted for the increases in C4 null and HLA alleles. To examine the role of specific AHs we undertook a longitudinal analysis of a subgroup of 26 patients who seroconverted under observation. Seventeen of these patients were followed for 32 to 63 months. All seven patients with the 8.1 AH (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1 AH. The acquired immunodeficiency syndrome developed in three further cases with either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and 35.x AHs contain deletions of the central major histocompatibility complex (MHC) genes, we suggest that the genes affecting HIV infection and progression are within the central MHC region.

Alleles

Multiple pneumatocoeles and bilateral tension pneumothoraces complicating pneumocystis pneumonia in AIDS.

Pneumatocoele and pneumothorax are uncommon complications of Pneumocystis carinii pneumonia. We report a patient with the Acquired Immune Deficiency Syndrome who developed multiple bilateral pneumatocoeles which we demonstrate to have ruptured leading to the subsequent bilateral tension pneumothoraces and to death. The computerised tomographic appearances, and histopathology of these unusual complications are presented. The literature on these manifestations is reviewed and management discussed.

Acquired Immunodeficiency Syndrome

Chain shortening of palmitic acid in human subjects.

Chain shortening of palmitic acid was examined in vivo by comparing oxidation rates of [1-13C]palmitate vs [16-13C]palmitate fed to four male subjects consuming a high-fat diet. For 9 d subjects were fed a diet of normal foods providing an energy intake equal to their estimated requirements. The diet provided (as energy) approximately 14% protein, 46% carbohydrate, and 40% fat at a P:S ratio of 0.25. Analysis of breath 13CO2 enrichment on day 3 permitted analysis of background 13C contribution from the test diet alone. On days 4 and 7 either [1-13C]palmitic acid or [16-13C]palmitic acid (9-13.5 mg/kg body wt) was fed with the breakfast meal. The whole-body rate of oxidation of [1-13C]palmitic acid was significantly greater than that observed for [16-13C]palmitic acid. These results suggest that up to 34% of dietary palmitic acid consumed may be subjected to extramitochondrial chain shortening.

Adult

Protein-losing enteropathy in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) presented with anasarca, pleural effusions and severe hypoalbuminema. Both were demonstrated to have protein-losing enteropathy, a rare complication of SLE. Other causes of gastrointestinal protein loss were excluded. There were marked similarities in both cases including circulating ANF with speckled staining, anti-(U1)RNP antibodies and low serum complement levels. Complete remission was achieved in both with prednisolone. Anti-(U1)RNP may be a marker for a subset of SLE in which protein-losing enteropathy is a major manifestation.

Adult

Platelet monoamine oxidase: low activity in cigarette smokers.

Platelet monoamine oxidase (MAO) activity and plasma thiocyanate concentration (an index of smoking behavior) were measured in 109 normal male and female volunteers. MAO activity was significantly lower and plasma thiocyanate concentration significantly higher in smoking volunteers than in nonsmoking volunteers. A significant negative correlation between MAO activity and thiocyanate concentration was observed in female smokers (rs = 0.43, n = 36) but not for male smokers (rs = 0.02, n = 31). In nine smokers who gave up smoking, mean (+/- SD) platelet MAO activity increased significantly (17.5 +/- 4.1 nmole/mg/hour to 24.6 +/- 4.2 nmole/mg/hour). At the same time, mean (+/- SD) plasma thiocyanate concentrations decreased significantly (144 +/- 41 microM to 50 +/- 12 microM). These data suggest that smoking directly or indirectly reduced platelet MAO activity.

Adolescent

Platelet monoamine oxidase activity in patients with Huntington's disease.

1. Platelet monoamine oxidase (MAO) activity was investigated in 30 patients with Huntington's disease and compared with the activity in a control group. 2. Significantly elevated activity was found in the patients (P less than 0.05; t-test) when same sex contrasts were carried out to account for the well known influence of sex on MAO activity. 3. The mean MAO activity in male patients was 23.5 +/- 6.0 nmol/mg protein per h and female patients was 29.5 +/- 8.9 nmol/mg protein per h using tyramine as the substrate. 4. The possible influence of environmental factors on the results is discussed.

Adolescent

Serum IgG subclasses in patients with an increased susceptibility to respiratory tract infections.

Serum IgG subclass concentrations were assayed in 45 patients with chronic respiratory tract infections and 16 patients with recurrent acute respiratory tract infections. Eleven of these 61 patients, all but one with recurrent acute infections, were IgA-deficient but the remainder had normal or high serum immunoglobulin concentrations. Only 4% of patients with chronic infections were IgG2-deficient. The prevalence of IgG2 deficiency amongst patients with recurrent acute infections was greater (31%), but in most cases this appeared to be due to an association with IgA deficiency. Owing to the limits of assay sensitivity it was not possible to determine whether any patient was IgG4-deficient, but the number of sera with undetectable IgG4 was greater in patients with recurrent acute infections than in controls (37.5% vs 10%, p less than 0.01), although such patients were mainly those with IgA and IgG2 deficiency. None of the patients had IgG1 or IgG3 deficiency; in fact IgG3 concentrations were higher than those of controls in both groups of patients (p less than 0.001) and IgG1 concentrations were higher than those of controls in patients with recurrent infections (p less than 0.01). Thus, unequivocal IgG subclass deficiency is uncommon in non-IgA-deficient patients, but those with IgG2 deficiency may have an immune defect requiring further investigation.

Adult

Immunoglobulin G subclass distribution of autoantibodies in systemic sclerosis, primary biliary cirrhosis, and overlap syndromes.

The IgG subclass reactivities of six anticellular antibodies were measured by indirect immunofluorescence on HEp2 cells using murine monoclonal antibodies to the four human IgG subclasses. Patients with scleroderma, primary biliary cirrhosis (PBC), systemic lupus erythematosus, and mixed connective tissue disease were studied. Anticentromere antibody (ACA) was virtually all IgG1 and 3; antibody to multiple nuclear dots (NSpI) was IgG1, 2, and 3; antimitochondrial antibody was mainly IgG2 and 3; nucleolar staining was varied in subclass reactivity but most often IgG4; the diffusely grainy staining associated with Scl-70 antibody was chiefly IgG1; and the speckled pattern associated with anti-RNP antibody was always IgG1 and 4, with IgG2 and 3 in some cases. These data fail to support the hypothesis that the various patterns of autoimmune disease reflect differences in the biological properties of the associated antibodies. The prominence of IgG2 in antibodies associated with PBC suggests the possibility of an immune response independent of T cells in that condition. Differential subclass staining showed an unexpectedly high frequency of antibody to multiple nuclear dots in ACA positive sera, and such patients (all with CREST syndrome) could be at increased risk of developing PBC later.

Antibodies, Antinuclear