Death from invasive meningococcal disease following close contact with a case of primary meningococcal conjunctivitis--Langley, British Columbia, 1999.
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Adult↗
Biomedical subjects
A J Pollard
Publications and source records attributed to A J Pollard.
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.
Antibodies, Bacterial↗
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.
Adolescent↗
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.
Adolescent↗
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.
Adult↗
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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Altitude Sickness↗
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.
CD18 Antigens↗
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.
Age Factors↗
A prospective evaluation of scrotal ultrasonography in clinical practice.
OBJECTIVES: To prospectively evaluate scrotal ultrasonography (SUS) in patients presenting with scrotal symptoms and to make recommendations about use of SUS in clinical practice. PATIENTS AND METHODS: Forty-eight men with scrotal symptoms were examined by a urologist and independently underwent SUS by one radiologist with no knowledge of the clinical diagnosis. The clinical and SUS diagnoses were compared and the effect on subsequent management recorded. RESULTS: The clinical and SUS diagnoses agreed in 35 men (73%) although SUS provided an additional diagnosis in half of these men. The SUS diagnosis differed in 13 men (27%) although the management was altered in only four patients. CONCLUSION: The clinical diagnosis is correct in most men with scrotal symptoms; the routine use of SUS is inappropriate and should be reserved for specific indications.
Adolescent↗
Serial changes in spirometry during an ascent to 5,300 m in the Nepalese Himalayas.
The aims of the present study were to determine the changes in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and peak expiratory flow (PEF), during an ascent to 5,300 m in the Nepalese Himalayas, and to correlate the changes with arterial oxygen saturation measured by pulse oximetry (SpO2) and symptoms of acute mountain sickness (AMS). Forty-six subjects were studied twice daily during an ascent from 2,800 m (mean barometric pressure 550.6 mmHg) to 5,300 m (mean barometric pressure 404.3 mmHg) during a period of between 10 and 16 days. Measurements of FVC, FEV1, PEF, SpO2, and AMS were recorded. AMS was assessed using a standardized scoring system. FVC fell with altitude, by a mean of 4% from sea level values [95% confidence intervals (CI) 0.9% to 7.4%] at 2,800 m, and 8.6% (95% CI 5.8 to 11.4%) at 5,300 m. FEV1 did not change with increasing altitude. PEF increased with altitude by a mean of 8.9% (95% CI 2.7 to 15.1%) at 2,800 m, and 16% (95% CI 9 to 23%) at 5,300 m. These changes were not significantly related to SpO2 or AMS scores. These results confirm a progressive fall in FVC and increase in PEF with increasing hypobaric hypoxia while FEV1 remains unchanged. The increase in PEF is less than would be predicted from the change in gas density. The fall in FVC may be due to reduced inspiratory force producing a reduction in total lung capacity; subclinical pulmonary edema; an increase in pulmonary blood volume, or changes in airway closure. The absence of a correlation between the spirometric changes and SpO2 or AMS may simply reflect that these measurements of pulmonary function are not sufficiently sensitive indicators of altitude-related disease. Further studies are required to clarify the effects of hypobaric hypoxia on lung volumes and flows in an attempt to obtain a unifying explanation for these changes.
Adult↗
Vaccines for prevention of meningococcal disease.
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Adolescent↗
Spatio-temporal expression of the trans-acting splicing factors SF2/ASF and heterogeneous ribonuclear proteins A1/A1B in the myometrium of the pregnant human uterus: a molecular mechanism for regulating regional protein isoform expression in vivo.
Many of the human myometrial proteins associated with uterine quiescence and the switch to coordinated contractions at the onset of labor exist as alternatively spliced isoforms. There is now extensive evidence to indicate that the nuclear concentrations of the trans-acting splicing regulators SF2/ASF and hnRNP A1/A1B are fundamental in regulating the expression of specific protein isoforms derived from alternative splicing of single precursor messenger ribonucleic acid transcripts. The question thus arose as to whether these factors were also involved in regulating the expression of specific myometrial protein species within different uterine regions during human gestation and parturition. SF2/ASF and hnRNP A1/A1B expression was therefore determined in paired upper (corpus) and lower segment myometrial samples taken from individual women at term/during spontaneous labor and compared with nonpregnant control samples using specific monoclonal antibodies. We report that SF2/ASF levels were substantially increased in the lower uterine region, and this was associated with a parallel decrease in levels of hnRNP A1/A1B during gestation. Conversely, the opposite pattern was observed within the upper uterine region during pregnancy, where hnRNP A1/A1B was significantly up-regulated and SF2/ASF levels were much less than those found in the lower uterine segment. The differential expression of hnRNP A1/A1B and SF2/ASF in the upper and lower uterine segments may have a primary role in defining the formation of specific myometrial protein species associated with the known contractile and relaxatory properties of these regions before and during parturition.
Alternative Splicing↗
Meningococcal disease and healthcare workers.
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Health Personnel↗
Assessment of immune response to meningococcal disease: comparison of a whole-blood assay and the serum bactericidal assay.
A whole-blood assay (WBA), which assesses the complete bactericidal activity of blood, was compared with the serum bactericidal assay (SBA), which measures antibody and complement mediated cell lysis. Twenty children infected with serogroup B strains and 25 infected with serogroup C strains were studied 8-12 weeks after disease, and 29 healthy children were used as controls. The infecting strain (convalescent children only) and two reference strains, MC58 (B:15:P1.7, 16) and NCTC 8554 (C:NT:P1.5) were used. In children previously infected with a serogroup B strain, bactericidal activity was detected in 95% and 85% to their infecting strain by the WBA (>50% killing) and the SBA (s), respectively. Bactericidal activity to the reference serogroup B and C strain was detected by WBA in 70 and 75% of children, respectively, and the SBA in 45% and 20%. In contrast bactericidal activity was detected to both serogroup C strains in >80% of children previously infected with a serogroup C strain using either assay and in 48% (WBA) and 20% (SBA) to the reference serogroup B strain. Levels of bactericidal activity were detectable in fewer control children. Children convalescing from meningococcal disease develop an immune response to their infecting strain, detectable by both the WBA and SBA, which is independent of age. However, the WBA appears to be a more sensitive measure of bactericidal activity to heterologous strains than the SBA.
Adolescent↗
The effect of high altitude on platelet counts, thrombopoietin and erythropoietin levels in young Bolivian airmen visiting the Andes.
Recognition of thrombosis as a complication of exposure to high altitude has stimulated interest in rheological changes resulting from hypobaric hypoxia. Previous studies of platelet counts at high altitude have yielded conflicting results and have not been studied in conjunction with potential mediating cytokines. We studied the effects of high-altitude exposure on platelet numbers, thrombopoietin (tpo) and erythropoietin (epo) levels in man. A group of 28 volunteers from the Bolivian Airforce stationed at Santa Cruz (600 m altitude) were studied 48 h and 1 week after their ascent to La Paz (3600 m). In addition 105 volunteers based at Santa Cruz for at least 1 year were compared with 175 age- and sex-matched residents at El Alto (4200 m). Platelet counts were measured immediately after sampling and serum samples assayed for tpo and epo. In the ascending group, mean platelet counts were 251 x 10(9), 367 x 10(9) and 398 x10 (9)/l at 600 m and following 48 h and 1 week at 3600 m respectively. Mean tpo levels were 132.5, 76 and 92 pg/ml with epo values of 2.98, 11.6 and 7.9 mIU/ml respectively. In the resident populations mean platelet counts were 271 x 10(9)/l in the low- and 471 x 10(9)/l in the high-altitude groups. Mean tpo and epo levels measured 69.3 pg/ml and 4.5 mIU/ml respectively at 600 m and 58.5 pg/ml and 5.1 mIU/ml at 4200 m. In conclusion we have demonstrated a significant and sustained elevation in platelet numbers within 48 h of ascent to high altitude. Our findings do not support a role for tpo as a mediator of the increased platelet count. However, these data do not discount epo as a potential candidate.
Adaptation, Physiological↗
Humoral immune responses to Neisseria meningitidis in children.
An understanding of the nature of immunity to serogroup B meningococci in childhood is necessary in order to establish the reasons for poor responses to candidate vaccines in infancy. We sought to examine the nature of humoral immune responses following infection in relation to age. Serum bactericidal activity was poor in children under 12 months of age despite recent infection with Neisseria meningitidis. The highest levels of bactericidal activity were seen in children over 10 years of age. However, infants produced levels of total immunoglobulin G (IgG) and IgG subclass antibodies similar to those in older children in a meningococcal enzyme-linked immunosorbent assay. Most antibody was of the IgG1 and IgG3 subclasses. This striking age dependency of bactericidal antibody response following infection is not apparently due to failure of class switching in infants but might be due to qualitative differences in antibody specificity or affinity.
Adult↗
Cellular immune responses to Neisseria meningitidis in children.
There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.
Adult↗
Emergency management of meningococcal disease.
Meningococcal disease remains a major cause of mortality in children in the UK. Aggressive early volume resuscitation, meticulous attention to the normalisation of all physiological and laboratory parameters, and prompt referral to specialist paediatric intensive care may lead to a sharp reduction in mortality. Application of the management algorithm described in this article may be helpful to those involved in the early part of management of critically ill patients with meningococcal disease.
Algorithms↗