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Biomedical subjects

S B Gordon

Publications and source records attributed to S B Gordon.

At least 19 recordsLinked to original sources
PubMed2002

Macrophage defences against respiratory tract infections.

Pulmonary macrophages with a key role in defence against respiratory infection are a heterogeneous family of cells with phagocytic, antigen processing and immunomodulatory functions. Macrophages are important in both innate and acquired immunity in the respiratory tract, and have a role in lung defence against viruses, bacteria, mycobacteria and fungi. Interactions of pathogens with lung macrophages is strongly influenced by soluble immune components including complement, collectins and immunoglobulins. Macrophage function can be modulated by cytokines, environmental exposures, recent and chronic infection including HIV infection, drug therapy and gene transfer.

Bacterial Infections↗
PubMed2001

Opsonic phagocytosis of Streptococcus pneumoniae by alveolar macrophages is not impaired in human immunodeficiency virus-infected Malawian adults.

Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis, especially among adults infected with the human immunodeficiency virus (HIV). Alveolar macrophages (AMs) are critical components of cellular defense against bacterial infection and are both infected and affected by HIV. In this study, AMs obtained at bronchoscopy from 44 Malawian adults (24 HIV positive and 20 HIV negative) were exposed in vitro to opsonized S. pneumoniae and coagulase-negative staphylococci. AMs from HIV-positive and -negative volunteers showed no significant difference in binding to or internalization of either S. pneumoniae or coagulase-negative staphylococci. In HIV-positive subjects, the presence of detectable HIV in lung fluid was not associated with AM impairment. AMs from HIV-infected adults did not exhibit impaired pneumococcal phagocytosis in the assay used. This suggests that an alternative mechanism of susceptibility is operating in these individuals.

Adult↗
PubMed2001

Bacteraemia and mortality among adult medical admissions in Malawi--predominance of non-typhi salmonellae and Streptococcus pneumoniae.

OBJECTIVES: The high seroprevalence of HIV in Malawi might be expected to alter the pattern of pathogens isolated from bacteraemic patients. We aimed to describe the frequency and seasonal pattern of bacterial isolates from blood, their antibiotic susceptibility, and patient outcome, in order to provide data on which to base empirical antibiotic therapy and further studies of pathogenesis. METHODS: Over a 12-month period, blood cultures were taken from all febrile adult medical admissions to Queen Elizabeth Central Hospital, Blantyre. RESULTS: A total of 2789 out of 9298 adult general medical admissions had blood culture performed, of whom 449 (16.1%) grew significant pathogens. Non-typhi salmonellae (NTS) (37%) and Streptococcus pneumoniae (30%) were the two commonest isolates. Mortality was 18% among general medical admissions and 38% among bacteraemic patients. Mortality for individual pathogens was: NTS 33%; S. pneumoniae 36%; Escherichia coli 54%; Klebsiella spp. 58%; Neisseria meningitidis 44%; Salmonella typhi 17%. Despite an overwhelming association between the major pathogens and HIV infection (95% of S. pneumoniae cases and 92% of NTS cases were seropositive for HIV), a seasonal pattern was preserved. Streptococcus pneumoniae was more frequently isolated in the cold dry months, while STM isolates increased following a rise in temperature. A case of bacteraemia with Vibrio cholerae (serotype 01) was detected during a cholera outbreak in the rainy season. Although S. pneumoniae isolates were relatively susceptible to penicillin (88%) and chloramphenicol (74%), S. typhimurium isolates were fully susceptible only to chloramphenicol. CONCLUSIONS: This large study confirms the dominance of NTS and S. pneumoniae in bacteraemia in an area affected by HIV-1 and allows comparison of mortality by individual pathogens. It demonstrates a preserved seasonal pattern of bacteraemia for these major pathogens, despite an overwhelming association with HIV infection.

Adolescent↗
PubMed2001

Changes in availability of oxygen accentuate differences in capsular polysaccharide expression by phenotypic variants and clinical isolates of Streptococcus pneumoniae.

Most isolates of Streptococcus pneumoniae are mixed populations of transparent (T) and opaque (O) colony phenotypes. Differences in the production of capsular polysaccharide (CPS) between O and T variants were accentuated by changes in the environmental concentration of oxygen. O variants demonstrated a 5.2- to 10.6-fold increase in amounts of CPS under anaerobic compared to atmospheric growth conditions, while CPS production remained low under all conditions for T variants. Increased amounts of CPS in O compared to T pneumococci were associated with increased expression of cps-encoded proteins. The inhibitory effect of oxygen on expression of CPS in O variants correlated with decreased tyrosine phosphorylation of CpsD, a tyrosine kinase and regulator of CPS synthesis. Modulation of CpsD expression and its activity by tyrosine phosphorylation may allow the pneumococcus to adapt to the requirements of both colonization, where decreased CPS allows for adherence, and bacteremia, where increased CPS may be required to escape from opsonic clearance. In patients with invasive infection, paired isolates from the same patient were shown to have predominantly a T colony phenotype without phosphotyrosine on CpsD when cultured from the nasopharynx, and an O phenotype that phosphorylates CpsD in response to oxygen when cultured from the blood. Differences in the availability of oxygen, therefore, may be a key factor in allowing for the selection of distinct phenotypes in these two host environments.

Bacteremia↗
PubMed2000

Bacterial meningitis in Malawian adults: pneumococcal disease is common, severe, and seasonal.

We prospectively collected laboratory details and outcome data on all patients with laboratory-confirmed cases of meningitis that presented to our unit in Blantyre, Malawi, from 1 April 1998 through 31 March 1999. There were 502 patients with cases of meningitis; the most common causative organisms were Cryptococcus neoformans and Streptococcus pneumoniae. This pattern probably reflects the local human immunodeficiency virus (HIV) seroprevalence (31%) and is different from the pattern in 1974, when Neisseria meningitidis was the most common isolate. There has been an 8-fold increase in the number of meningitis cases per year since 1974, and a doubling of the percentage of medical admissions due to meningitis. The inpatient mortality rate among patients with cases of pneumococcal meningitis was 61%, and in the group as a whole was 41%. Despite the HIV-related pattern of infecting pathogens among these cases of meningitis and the increased incidence of the condition, there was evidence that the typical seasonal pattern of pneumococcal meningitis, which peaks in the cold, dry season, was preserved.

Adult↗
PubMed2000

Intracellular trafficking and killing of Streptococcus pneumoniae by human alveolar macrophages are influenced by opsonins.

Human alveolar macrophages (HAM) are the major resident phagocytic cells of the gas-exchanging areas of the lung. Following contact with macrophages, bacteria enter phagosomes, which gradually acquire the characteristics of terminal phagolysosomes, with incorporation of lysosome-associated membrane protein (LAMP). We measured the binding of type 1 Streptococcus pneumoniae to the surface of HAM and then measured subsequent internalization and phagosomal incorporation of LAMP-1 under various opsonic conditions. Opsonization with serum containing immunoglobulin resulted in significantly greater binding of pneumococci to HAM compared with opsonization with immunoglobulin G (IgG)-depleted serum containing complement, which in turn resulted in marginally increased binding over that observed in the absence of opsonization. Internalization of opsonized S. pneumoniae gradually increased to a maximum of 20% of bound bacteria by 120 min of warm incubation, with 20% of internalized pneumococci being localized within LAMP-containing compartments by 80 min. Internalization of opsonized S. pneumoniae by HAM correlated with a reduction of bacterial viability. When inocula were adjusted so that pneumococcal binding under different conditions was equalized, subsequent internalization, trafficking to LAMP-containing compartments, and reduction of bacterial viability were less efficient in the absence of opsonization than that observed following opsonization with adsorbed or IgG-replete adsorbed serum. Once bound to the surface of HAM, pneumococci opsonized with adsorbed serum with or without IgG were internalized, processed, and killed equally well. In conclusion, binding, intracellular trafficking, and killing of S. pneumoniae by HAM are each significantly increased by opsonization with serum containing immunogloblin and/or complement.

Antigens, CD↗
PubMed1998

Respiratory symptoms among glass bottle workers--cough and airways irritancy syndrome?

Glass bottle workers have been shown to experience an excess of respiratory symptoms. This work describes in detail the symptoms reported by a cohort of 69 symptomatic glass bottle workers. Symptoms, employment history and clinical investigations including radiology, spirometry and serial peak expiratory flow rate records were retrospectively analyzed from clinical records. The results showed a consistent syndrome of work-related eye, nose and throat irritation followed after a variable period by shortness of breath. The latent interval between starting work and first developing symptoms was typically 4 years (median = 4 yrs; range = 0-28). The interval preceding the development of dysponea was longer and much more variable (median = 16 yrs; range = 3-40). Spirometry was not markedly abnormal in the group but 57% of workers had abnormal serial peak expiratory flow rate charts. Workers in this industry experience upper and lower respiratory tract symptoms consistent with irritant exposure. The long-term functional significance of these symptoms should be formally investigated.

Adult↗
PubMed1997

Screening questionnaires for bakers' asthma--are they worth the effort?

The use of a respiratory screening questionnaire is recommended annually to screen bakery workers in the UK. We compared questionnaire screening with other methods of detecting workers with asthmatic symptoms and then assessed the significance of these symptoms with careful investigation and follow-up. Reasons for questionnaire failures were then explored. A questionnaire was issued to 362 flour-exposed workers in a large bakery. All positive respondents to respiratory symptom questions were interviewed by an occupational nurse. Workers with occupationally related symptoms at this interview were referred to the chest clinic. In addition, workers with negative questionnaires were screened using attendance records, sick notes and direct workplace observations. Workers with frequent absence from work or sick notes with respiratory diagnoses were interviewed in the same manner as those answering the questionnaire positively and then referred to clinic. At clinic, a diagnosis was made for each worker on the basis of clinical assessment, spirometry, serial peak expiratory flow rate (PEFR) analysis and radioallergosorbent testing (RAST) testing for specific IgE. Using the clinic diagnoses, the referral routes were audited to assess the rates of case detection of asthma and occupational asthma. The respiratory screening questionnaire identified 68 workers with respiratory symptoms. Of these, 21 proceeded to full assessment. A diagnosis of asthma was made in five cases, one of which was bakers' asthma. In addition, 11 workers not reporting any symptoms by questionnaire were referred to clinic and five were diagnosed as having asthma. Screening questionnaires may lead to an underestimate of the prevalence of asthmatic symptoms and as such should not be used alone in workplace screening.

Adult↗
PubMed1997

Glass bottle workers exposed to low-dose irritant fumes cough but do not wheeze.

Workers exposed to irritant fumes experience symptoms both during the acute episode and afterwards. High-dose irritant exposure can result in permanent asthma, but the effects of chronic low-dose irritant exposure are not known. Glass bottle workers are exposed to irritant fumes, and have previously been reported to have an excess of symptoms. We designed a study to compare irritant-exposed glass bottle workers with hospital workers matched for socioeconomic group, area of residence, age, sex, smoking habit, and allergic history. Symptoms reported, spirometry, flow cytometric indices of lymphocyte activation, and past medical and employment histories were compared. We also investigated the prevalence of bronchial hyperresponsiveness to inhaled methacholine and the cough response after inhalation of citric acid and capsaicin. Glass bottle workers showed an excess of upper respiratory tract symptoms, cough, and shortness of breath compared with matched hospital control workers. There was a significant excess of cough induced by citric acid and capsaicin in the bottle workers. However, wheeze, baseline spirometry, flow cytometry, and methacholine challenge were not significantly different between the two groups. These findings suggest that chronic irritant exposure produces an excess of symptoms and increased cough sensitivity but not asthma.

Adult↗
PubMed1997

Irritant exposure, bronchial reactivity and asthma.

The role of irritant exposure in the pathogenesis of bronchial reactivity and asthma is uncertain. This paper reviews the evidence from environmental epidemiological surveys, studies of occupationally exposed populations and chamber studies of asthmatic and nonasthmatic subjects exposed to irritant fumes. The reactive airways dysfunction syndrome and occupational asthma due to irritant exposure are considered in the context of these results. Although several irritants cause acute bronchoconstriction by a number of mechanisms in chamber studies, there is little convincing evidence to suggest that irritant exposure without pulmonary injury is a risk factor for the development of bronchial hyperresponsiveness. This is the case both in relatively intense concentrations, such as those experienced in industrial or chamber exposure, and at the levels experienced by the general population.

Air Pollutants, Occupational↗
PubMed1979

Responsive parenting: an approach to training parents of problem children.

Two behavior modification groups for parents of problem children between the ages of two and ten were conducted along the lines of the Responsive Teaching Model. The two groups met for 10 and 8 weeks, respectively, with six families represented in each group. In Responsive Parenting (RP), parents are taught to observe and measure their children's problematic behavior. Subsequently, each parent develops a home project designed to modify this behavior; 11 of the 12 parents developed a successful home project. In addition, the attendance was approximately 90% and the completion of weekly assignments was close to 100%. Paper-and-pencil measures revealed that the parents were very satisfied with the parent-training group and rated their children as improved on a bipolar adjective checklist. These results are discussed with regard to implications for the delivery of mental health services for children. Future research directions are delineated.

Adult↗