Biomedical subjects
A J Pollard
Publications and source records attributed to A J Pollard.
Clinical features of headache at altitude: a prospective study.
BACKGROUND: Headache is the most common nervous system complication at altitude; however, there have been few attempts to characterize clinical features of high-altitude headaches (HAH). OBJECTIVE: To measure prospectively the incidence of HAH and to determine its risk factors and characteristics. METHODS: Members of an expedition to Kanchenjunga base camp in Nepal (5,100 m) were prospectively studied. Subjects were interviewed prior to the trip and while trekking recorded headaches experienced at >3,000 m using a structured questionnaire incorporating International Headache Society (IHS) and acute mountain sickness (AMS) criteria. In addition, clinical features of headaches in 19 trekkers in other groups above 3,000 m were recorded using the same questionnaire. RESULTS: Eighty-three percent (50/60) reported at least 1 HAH (median 2, range 0 to 10). Those who developed HAH were younger (p = 0.04); women and persons with headaches in daily life were more likely to report severe headaches (p = 0.03 and p = 0.07). One hundred thirty-eight HAH, experienced by 69 persons, are described. The mean altitude at which headaches occurred was 4,723 m. Twenty-six percent of headaches woke subjects at night or occurred upon awakening. HAH reported by migraineurs were accompanied by more phonophobia (p = 0.008). There were no IHS accompanying symptoms in 44% of headaches or symptoms of AMS in 52% of headaches. CONCLUSIONS: Headaches are a frequent complication of ascent to altitude. Older age appears to offer some protection, whereas headaches were more severe in women and persons with headaches in daily life. There is a wide clinical spectrum, with some suggesting intracranial hypertension. There is a need for evidence-based diagnostic criteria for headaches at altitude.
Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure.
AIMS: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. METHODS: Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. RESULTS: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15); unvaccinated GMC 1.48 microg/ml (0.90 to 2.21); p = 0.003). CONCLUSIONS: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.
The future of meningitis vaccines.
Without effective vaccines meningitis remains a substantial worldwide threat with major health-care implications. A number of advances have been made in vaccine design and implementation over the last decade, with new vaccine initiatives providing substantial promise for the future reduction of global disease burden.
Respiratory syncytial virus infections in children and adults.
Respiratory syncytial virus is the leading cause of hospital admission for lower respiratory tract infection in young children and appears to be responsible for a significant burden of disease in adults, particularly the elderly and the immunocompromised. In this review, we describe the epidemiology, diagnosis and clinical manifestations of infection attributed to this virus. We also consider current therapeutic and prophylactic options and appraise strategies for vaccination that are in clinical trials.
Pelvic inflammatory disease associated with Enterobius vermicularis.
A case of pelvic inflammatory disease in a sexually non-active 13 year old girl is described, with evidence of pinworms as the cause. Albendazole treatment cleared the infestation but the patient suffered subsequent bouts of lower abdominal pain. The literature is reviewed regarding abdominal pathology associated with ectopic migration of pinworms.
The meningococcus tamed?
Serogroup B Neisseria meningitidis is a frequent cause of invasive meningococcal disease, yet there are no effective vaccines suitable for routine immunisation. Limited efficacy has been shown with meningococcal outer membrane vacccines in children 4 years and older. Here we review the status of current research and consider new approaches to development of meningococcal serogroup B vaccines.
Increased resting bronchial tone in normal subjects acclimatised to altitude.
BACKGROUND: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms. METHODS: BHR to histamine was measured using a turbine spirometer to record partial and full flow-volume curves and expressed as log dose slopes. Twenty one subjects were tested at sea level and after acclimatisation at 5000 m altitude. RESULTS: No significant change in log dose slope measurements of forced expiratory volume in 1 second occurred after acclimatisation, and the maximal expiratory flow with 30% of forced vital capacity remaining (MEF(30%)) rose on the full loop and fell on the partial loop. Their ratio (full divided by partial) rose on average by 0.28 (95% confidence limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20). CONCLUSIONS: There is no increase in BHR in normal subjects acclimatised to altitude but an increase in resting bronchial tone occurs that could be released by deep inspiration. This may be the result of increased cholinergic tone.
Vaccine prevention of meningococcal disease, coming soon?
The past century has seen the use of a number of vaccines for prevention and control of meningococcal disease with varied success. The use of polysaccharide vaccines for the control of outbreaks of serogroup C infections in teenagers and young adults and epidemic serogroup A disease has been established for 30 years and an effective protein-polysaccharide conjugate vaccine against serogroup C was introduced into the UK infant immunisation schedule in 2000. The next generation of these glycoconjugate vaccines will be on the shelf soon, eventually offering the prospect of eradication of serogroups A, C, Y and W135 through routine infant immunisation. Despite these exciting prospects, serogroup B meningococci still account for a majority of infections in industrialised nations but development of safe, immunogenic and effective serogroup B meningococcal vaccines has been an elusive goal. Outer membrane vesicle vaccines for B disease are already used in some countries, and will likely be used more widely in the next few years, but efficacy for endemic disease in children has so far been disappointing. However, the innovations arising from the availability of the meningococcal genome sequence, public and scientific interest in the disease and recent pharmaceutical company investment in development of serogroup B vaccines may have started the countdown to the end of meningococcal infection in children.
Two distinct receptors mediate nonopsonic phagocytosis of different strains of Pseudomonas aeruginosa.
Complement receptor 3 (CR3) mediates both opsonic and nonopsonic phagocytosis of bacteria. Leukocyte adhesion deficiency (LAD) allows for the study of CR3-dependent phagocyte-bacterial ingestion, since LAD phagocytes do not express this receptor. Phagocytes from an infant with LAD were unable to ingest 50% of the Pseudomonas aeruginosa strains studied, which indicates a requirement for CR3. However, the remaining strains were phagocytosed in the absence of CR3, and ingestion was blocked by monoclonal antibodies directed at CD14. This CR3/CD14 receptor bias was further confirmed by using thioglycollate-elicited murine peritoneal macrophages, which have nonfunctional CR3 before activation. Results indicate that either CR3 or CD14 is involved independently in nonopsonic phagocytosis of different P. aeruginosa strains. Clearance of P. aeruginosa from the endobronchial space may be facilitated by nonopsonic phagocytosis, since low levels of opsonins are present. The impact of lung infection with P. aeruginosa may be determined, in part, by the phagocytic receptor that mediates ingestion.
Death from invasive meningococcal disease following close contact with a case of primary meningococcal conjunctivitis--Langley, British Columbia, 1999.
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Development of natural immunity to Neisseria meningitidis.
Although meningococcal disease is rare in industrialized nations, Neisseria meningitidis holds a prominent position amongst pediatric infections because of the dramatic clinical presentation of the disease, high mortality, epidemic potential and the recent disappearance of many other important infectious diseases in developed countries through improvements in public health and vaccination. The precise nature of natural immunity to meningococci remains unknown, although a complex interaction between the organism and nasopharyngeal mucosal barrier, innate immune mechanisms and acquired immunity is involved. Study of the mechanisms of natural immunity may provide the key to development of vaccines that can reduce the burden of disease in early childhood.
Meningococcal disease and vaccination in North America.
In North America, meningococcal disease occurs at a rate of I case per 100000 population per year, producing 2725 cases notified in the US in 1998 and 155 laboratory confirmed cases in Canada in the same year. A majority of these cases occur in the winter season and in early childhood, with a case fatality rate of approximately 10%. There has been an increase in the proportion of cases due to serogroup Y meningococci over the past decade: in 1995-98 in the US, 33% of cases were due to serogroup B, 28% were due to serogroup C and 34% were due to serogroup Y; in Canada in 1995-96, 47% of cases were due to serogroup B, 40% were due to serogroup C and 10% were due to serogroup Y. Outbreaks due to serogroup C were more common in the 1990s in the US and a number of outbreaks have occurred in Canada due to organisms from the hypervirulent ET-37 complex. College freshmen in the US in dormitories were found to be at an increased risk of disease. In addition, over the past 10 years, an outbreak of serogroup B disease occurred in the Pacific North-west of the US, with a fourfold increased rate of disease in that region. The explanations for these changes in epidemiology are unknown, but probably reflect the appearance of hypervirulent clones of meningococci and/or changing levels of population immunity. Meningococcal serogroup C polysaccharide-protein conjugate vaccines have been introduced recently in the UK, seem efficacious and offer the potential to reduce the burden of disease in the US and Canada too. Because serogroups other than serogroup C are prevalent in North America, a combination polysaccharide-protein vaccine, including C, Y and possibly W135 serogroups, would be attractive for this population. Although not currently an issue in industrialized nations, inclusion of serogroup A conjugates in any future vaccine policy would be an important decision in driving global prevention of meningococcal disease. A meningococcal conjugate vaccine against serogroup C was licensed in Canada in April 2001.
The long-term results of Anderson-Hynes pyeloplasty.
OBJECTIVES: To examine the durability of open pyeloplasty for pelvi-ureteric junction obstruction. PATIENTS AND METHODS: The records of 56 Anderson-Hynes pyeloplasties undertaken by two surgeons between 1981 and 1994 were examined. Attempts were made to trace all patients and for them to undergo diuretic renography to examine the current status of the operated renal unit. RESULTS: In all, 41 evaluable patients were identified; 24 agreed to return for reassessment. The mean (range) time from surgery was 10.6 (6-19) years. The results showed an improvement over the preoperative split renal function in 19 patients (79%) and an improvement in drainage in 23 (96%). CONCLUSIONS: The Anderson-Hynes pyeloplasty is an excellent procedure for treating pelvi-ureteric junction obstruction, and produces a lasting improvement in function and drainage in most patients. It is the 'gold standard' against which newer techniques should be compared.
The choice of timing for diuresis renography: the F + 0 method.
OBJECTIVE: To investigate a method of diuresis renography where the radiopharmaceutical and frusemide (diuretic) are given simultaneously, in contrast to conventional renography which involves an intravenous injection with frusemide 20 min after administering the radiopharmaceutical (F + 20) or 15 min before (F - 15), with particular interest in the effect of this change on assessing split renal function and interpreting upper tract drainage dynamics. PATIENTS AND METHODS: In a prospective study, 29 patients (18 women and 11 men, mean age 47 years, range 21--86) were assessed. Each patient had two renograms taken over a 48-h period, either by the F + 20 or F - 15, and the F + 0 method: Data for split renal function and drainage curves were obtained in the usual way. Two independent assessments of the drainage curves were obtained and the results compared. RESULTS: The split function assessments were identical (< 5% variation) in all but two patients; 26 of 29 (90%) gave identical conclusions about the drainage curves. The three patients with discrepancies between the studies had either hugely dilated upper tracts or otherwise had multiple complicating factors, e.g. impaired renal function, neuropathic bladder. CONCLUSIONS: F + 0 renography has been used in paediatric urological practice before, but there are no comparative studies and no data on its use in adults. This prospective study confirmed that in investigating dilated upper tracts, the F + 0 technique gives similar results to the conventional techniques. The F + 0 method has the potential to reduce the time required to undertake standard F + 20 renography but it may not be useful in evaluating the grossly dilated upper tract, where the F-15 technique has the best record in terms of reducing equivocal results.
Children at high altitude: an international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001.
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Nonopsonic phagocytosis of Pseudomonas aeruginoas: insights from an infant with leukocyte adhesion deficiency.
Children with leukocyte adhesion deficiency type I are at risk for overwhelming infection because their neutrophils lack surface beta 2 integrins (CD18/CD11) that normally interact with endothelial cell adhesion molecules and mediate migration to sites of bacterial invasion. In vitro studies of phagocytic cells from an infant with leukocyte adhesion deficiency type I demonstrated that complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some Pseudomonas aeruginosa strains and might play a control role in the control of Pseudomonas infections at sites where there are low levels of opsonins.
Production of low-avidity antibody by infants after infection with serogroup B meningococci.
Experimental serogroup B meningococcal vaccines have induced only poor immune responses and have had little protective efficacy in children younger than 1 year of age. We used ELISA with potassium thiocyanate to compare the average avidity of antibody produced by infants with that of children older than 10 years after systemic disease. Infants produced specific antibody of lower average avidity than older children--a finding that correlates with absence of serum bactericidal activity in the serum samples of the same infants.