Vascular plants are often considered to be among the better known large groups of organisms, but gaps in the available baseline data are extensive, and recent estimates of total known (described) seed plant species range from 200 000 to 422 000. Of these, global assessments of conservation status using International Union for the Conservation of Nature (IUCN) categories and criteria are available for only approximately 10 000 species. In response to recommendations from the Conference of the Parties to the Convention on Biological Diversity to develop biodiversity indicators based on changes in the status of threatened species, and trends in the abundance and distribution of selected species, we examine how existing data, in combination with limited new data collection, can be used to maximum effect. We argue that future work should produce Red List Indices based on a representative subset of plant species so that the limited resources currently available are directed towards redressing taxonomic and geographical biases apparent in existing datasets. Sampling the data held in the world's major herbaria, in combination with Geographical Information Systems techniques, can produce preliminary conservation assessments and help to direct selective survey work using existing field networks to verify distributions and gather population data. Such data can also be used to backcast threats and potential distributions through time. We outline an approach that could result in: (i) preliminary assessments of the conservation status of tens of thousands of species not previously assessed, (ii) significant enhancements in the coverage and representation of plant species on the IUCN Red List, and (iii) repeat and/or retrospective assessments for a significant proportion of these. This would result in more robust Sampled Red List Indices that can be defended as more representative of plant diversity as a whole; and eventually, comprehensive assessments at species level for one or more major families of angiosperms. The combined results would allow scientifically defensible generalizations about the current status of plant diversity by 2010 as well as tentative comments on trends. Together with other efforts already underway, this approach would establish a firmer basis for ongoing monitoring of the status of plant diversity beyond 2010 and a basis for comparison with the trend data available for vertebrates.
global biodiversity; species richness; conservation assessments; extinction risk; IUCN Red List; Living Planet Index
Serotonin receptor (5-HTR) agonists that target 5-HT4(a)R and 5-HT1AR can reverse μ-opioid receptor (μ-OR)-evoked respiratory depression. Here, we have tested whether such rescuing by serotonin agonists also applies to the cardiovascular system. In working heart–brainstem preparations in situ, we have recorded phrenic nerve activity, thoracic sympathetic chain activity (SCA), vascular resistance and heart rate (HR) and in conscious rats, diaphragmatic electromyogram, arterial blood pressure (BP) and HR via radio-telemetry. In addition, the distribution of 5-HT4(a)R and 5-HT1AR in ponto-medullary cardiorespiratory networks was identified using histochemistry. Systemic administration of the μ-OR agonist fentanyl in situ decreased HR, vascular resistance, SCA and phrenic nerve activity. Subsequent application of the 5-HT1AR agonist 8-OH-DPAT further enhanced bradycardia, but partially compensated the decrease in vascular resistance, sympathetic activity and restored breathing. By contrast, the 5-HT4(a)R agonist RS67333 further decreased vascular resistance, HR and sympathetic activity, but partially rescued breathing. In conscious rats, administration of remifentanyl caused severe respiratory depression, a decrease in mean BP accompanied by pronounced bradyarrhythmia. 8-OH-DPAT restored breathing and prevented the bradyarrhythmia; however, BP and HR remained below baseline. In contrast, RS67333 further suppressed cardiovascular functions in vivo and only partially recovered breathing in some cases. The better recovery of μ-OR cardiorespiratory disturbance by 5-HT1AR than 5-HT4(a)R is supported by the finding that 5-HT1AR was more densely expressed in key brainstem nuclei for cardiorespiratory control compared with 5-HT4(a)R. We conclude that during treatment of severe pain, 5-HT1AR agonists may provide a useful tool to counteract opioid-mediated cardiorespiratory disturbances.
cardiovascular control; neural control of breathing; apnoea; apneusis; cardio-sympathetic coupling; in vivo awake
Mammalian central pattern generators producing rhythmic movements exhibit robust but flexible behavior. However, brainstem network architectures that enable these features are not well understood. Using precise sequential transections through the pons to medulla, it was observed that there was compartmentalization of distinct rhythmogenic mechanisms in the ponto-medullary respiratory network, which has rostro-caudal organization. The eupneic 3-phase respiratory pattern was transformed to a 2-phase and then to a 1-phase pattern as the network was physically reduced. The pons, the retrotrapezoid nucleus and glycine mediated inhibition are all essential for expression of the 3-phase rhythm. The 2-phase rhythm depends on inhibitory interactions (reciprocal) between Bötzinger and pre-Bötzinger complexes, whereas the 1-phase-pattern is generated within the pre-Bötzinger complex and is reliant on the persistent sodium current. In conditions of forced expiration, the RTN region was found to be essential for the expression of abdominal late expiratory activity. However, it is unknown whether the RTN generates or simply relays this activity. Entrained with the central respiratory network is the sympathetic nervous system, which exhibits patterns of discharge coupled with the respiratory cycle (in terms of both gain and phase of coupling) and dysfunctions in this coupling appear to underpin pathological conditions. In conclusion, the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors.
retrotrapezoid nuclei; Bötzinger Complex; abdominal nerve
Background and Aims
Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) >400 μg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.
Children recorded as prescribed FP ⩾500 μg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response >500 nmol/l); impaired (peak cortisol ⩽500 nmol/l); or flat (peak cortisol ⩽500 nmol/l with increment of <200 nmol/l and basal morning cortisol <200 nmol/l).
A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6–19.3 years) were successfully tested. Of 194 receiving FP ⩾500 μg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of ⩾ 1000 μg/day.
Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving ⩾1000 μg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.
asthma; adrenal suppression; high dose inhaled corticosteroids; fluticasone propionate
A socioeconomic gradient in childhood obesity is known to be present by the age of school entry in the UK. The origin of this gradient is unclear at present, but must lie in socioeconomic differences in habitual physical activity, sedentary behaviour, or dietary intake.
To test the hypothesis that habitual physical activity and/or sedentary behaviour are associated with socioeconomic status (SES) in young Scottish children.
Observational study of 339 children (mean age 4.2 years, SD 0.3) in which habitual physical activity and sedentary behaviour were measured by accelerometry over six days (study 1). In a second study, 39 pairs of children of distinctly different SES (mean age 5.6 years, SD 0.3) were tested for differences in habitual physical activity and sedentary behaviour by accelerometry over seven days.
In study 1, SES was not a significant factor in explaining the amount of time spent in physical activity or sedentary behaviour once gender and month of measurement were taken into account. In study 2, there were no significant differences in time spent in physical activity or sedentary behaviour between affluent and deprived groups.
Results do not support the hypothesis that low SES in young Scottish children is associated with lower habitual physical activity or higher engagement in sedentary behaviour.
social inequalities; sedentary behaviour; energy metabolism; obesity
Mammalian central pattern generators (CPGs) producing rhythmic movements exhibit extremely robust and flexible behavior. Network architectures that enable these features are not well understood. Here we studied organization of the brain stem respiratory CPG. By sequential rostral to caudal transections through the pontine-medullary respiratory network within an in situ perfused rat brain stem–spinal cord preparation, we showed that network dynamics reorganized and new rhythmogenic mechanisms emerged. The normal three-phase respiratory rhythm transformed to a two-phase and then to a one-phase rhythm as the network was reduced. Expression of the three-phase rhythm required the presence of the pons, generation of the two-phase rhythm depended on the integrity of Bötzinger and pre-Bötzinger complexes and interactions between them, and the one-phase rhythm was generated within the pre-Bötzinger complex. Transformation from the three-phase to a two-phase pattern also occurred in intact preparations when chloride-mediated synaptic inhibition was reduced. In contrast to the three-phase and two-phase rhythms, the one-phase rhythm was abolished by blockade of persistent sodium current (INaP). A model of the respiratory network was developed to reproduce and explain these observations. The model incorporated interacting populations of respiratory neurons within spatially organized brain stem compartments. Our simulations reproduced the respiratory patterns recorded from intact and sequentially reduced preparations. Our results suggest that the three-phase and two-phase rhythms involve inhibitory network interactions, whereas the one-phase rhythm depends on INaP. We conclude that the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors.
Background: A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress.
Methods: Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events.
Results: An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69 (p = 0.00). In the period 3–10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 was found 5–7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children.
Conclusion: The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5–7 weeks later.
histiocytosis; Langerhans cell; orbit; tumour
Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes.
depression; hippocampus; prefrontal cortex; raphe; 5-HT; vagus; ANOVA, analysis of variance; AP, area postrema; c-Fos-ir, c-Fos-like-immunoreactive; DR, dorsal raphe nucleus; DRC, dorsal raphe nucleus, caudal part; DRI, dorsal raphe nucleus, interfascicular part; ECG, electrocardiogram; EDTA, ethylenediaminetetraacetic acid; EMG, electromyogram; HPLC, high pressure liquid chromatography; IL-6, interleukin-6; IL-10, interleukin-10; i.t., intratracheal; LPS, lipopolysaccharide; LSD, least significant difference; mlf, medial longitudinal fasciculus; M. vaccae, Mycobacterium vaccae; Mv-NC, Mycobacterium vaccae antigen, M. vaccae coupled to nitrocellulose beads; NC, nitrocellulose beads; nTS, nucleus of the solitary tract; OVA, ovalbumin; OVA-NC, ovalbumin coupled to nitrocellulose beads; PBG, phenylbiguanide; PBS, phosphate-buffered saline; PBST, phosphate-buffered saline containing 0.3% Triton X-100; RMg, raphe magnus; ROb, raphe obscurus; S.E.M., standard error of the mean; SolDL, dorsolateral part of the nucleus of the solitary tract; TGF-β, transforming growth factor-β; Th1, T helper cell 1; Th2, T helper cell 2; TNF-α, tumor necrosis factor-α; Treg, T regulatory cell; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin
BACKGROUND—In the past 10 years,
medication errors have come to be recognised as an important cause of
iatrogenic disease in hospital patients.
AIMS—To determine the incidence and
type of medication errors in a large UK paediatric hospital over a five
year period, and to ascertain whether any error prevention programmes
had influenced error occurrence.
METHODS—Retrospective review of
medication errors documented in standard reporting forms completed
prospectively from April 1994 to August 1999. Main outcome measure was
incidence of error reporting, including pre- and post-interventions.
RESULTS—Medication errors occurred
in 0.15% of admissions (195 errors; one per 662 admissions). While the
highest rate occurred in neonatal intensive care (0.98%), most errors
occurred in medical wards. Nurses were responsible for most reported
errors (59%). Errors involving the intravenous route were commonest
(56%), with antibiotics being the most frequent drug involved (44%).
Fifteen (8%) involved a tenfold medication error. Although 18 (9.2%)
required active patient intervention, 96% of errors were classified as minor at the time of reporting. Forty eight per cent of parents were
not told an error had occurred. The introduction of a policy of double
checking all drugs dispensed by pharmacy staff led to a reduction in
errors from 9.8 to 6 per year. Changing the error reporting form to
make it less punitive increased the error reporting rate from 32.7 to
38 per year.
CONCLUSION—The overall medication
error rate was low. Despite this there are clear opportunities to make
system changes to reduce error rates further.
clinical formulae (CF conference formula and estimation based on 120%
of average requirement for energy) have been recommended for the
estimation of energy requirements in cystic fibrosis but their accuracy
AIM—To compare the
accuracy of estimates of energy requirement derived from the two formulae.
requirement, defined as total daily energy expenditure, was measured
using the doubly labelled water method in 15 patients (six girls, nine
boys; mean (SD) age, 10.0 (2.4) years) who were well and clinically
stable. The accuracy of the formulae was assessed using calculation of
biases and limits of agreement relative to measured energy requirement.
the CF conference formula were lower than measured values (mean paired
difference, 0.52 MJ/day; 95% confidence interval (CI), −1.10 to
0.10), but this bias was not significant, and was smaller than that
from the alternative formula (mean paired difference, 0.77 MJ/day; 95%
CI, −0.20 to 1.74). Limits of agreement relative to measured total
daily energy expenditure were narrower for the CF conference formula
(−2.72 to 1.68 MJ/day) than for that based on 120% of estimated
average requirement (−2.75 to 4.29 MJ/day), but with both formulae
errors in estimation at the individual level were large.
conference formula offers improved prediction of energy requirements,
but the accuracy of both formulae at the individual level is not
sufficiently good for clinical purposes.
BACKGROUND: Re-admissions to hospital in childhood asthma are common with studies reporting that 25% or more of children will be re-admitted within a year. There is a need for strategies to reduce re-admissions. METHODS: A prospective randomised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma. Two hundred and one children were randomised at admission to either an intervention group (n = 96) which received the teaching programme or a control group (n = 105). A nurse- led teaching programme used the current attack as a model for the management of future attacks and included discussion, written information, subsequent follow up and telephone advice aimed at developing and reinforcing individualised asthma management plans. Parents were also provided with a course of oral steroids and guidance on when to start them. RESULTS: The groups were similar in degree of social deprivation, length of stay, number of previous admissions, acute asthma treatment, and asthma treatment at discharge. Subsequent re-admissions were significantly reduced in the intervention group from 25% to 8% in individual follow up periods that ranged from two to 14 months (chi 2 = 9.63; p = 0.002). This reduction was not accompanied by any increase in subsequent emergency room attendances nor, in the short term, by any increase in urgent community asthma treatment. The intervention group also showed significant reductions in day and night morbidity 3-4 weeks after admission to hospital. CONCLUSIONS: A nurse- led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma. Acute hospitalisation may be a particularly effective time to deliver home management training.
To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs.
Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom.
All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing.
141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school.
A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.
Key messagesThe number of children requiring long term ventilatory support has increased substantially in the past 8 yearsVentilatory support at home is the best option for meeting the child’s psychological needs and enhancing quality of lifeThe majority of children dependent on long term ventilation live at home and attend mainstream schoolsA shift of care has occurred from intensive care units to less acute areas
BACKGROUND--Previous studies have shown poor compliance with regular drug therapy in children and adults with asthma. In preschool children the parents supervise and are responsible for drug administration, but little is known of compliance in this group. In addition, there are few data on the patterns of drug use of inhaled prophylactic asthma therapy or of the relation between compliance and symptom control. A study was undertaken to address these issues with the hypothesis that parental supervision would result in good compliance. METHODS--The subjects were 29 asthmatic children aged 15 months to five years already established on inhaled prophylactic medication delivered through a large volume spacer. The prescribed drug regimens varied between subjects. This was an observational study using an electronic inhaler timer device to record the date and time of each actuation of the aerosol canister. Diary cards were used for parallel recording of symptoms and parentally reported compliance with a drug regimen. RESULTS--Variable and generally poor compliance was demonstrated with a median of 50% of study days with full compliance (subject range 0-94%) and an overall median of 77% of prescribed doses of therapy taken during the study period. No relation was found between frequency of prescribed regimen and good compliance. Day care was associated with poorer compliance. No relation between good compliance and low symptom scores was found. CONCLUSION--Compliance with inhaled prophylactic therapy is poor in preschool children with asthma whose medication is administered under parental supervision.
BACKGROUND--While there are reports on the outcome in adults and teenagers with cystic fibrosis of colonisation with Burkholderia (Pseudomonas) cepacia, there is little information in children. METHODS--In December 1991 only one of 115 children with cystic fibrosis attending a paediatric centre was colonised with B cepacia. Over the next 12 months there was a rapid increase with 23 (20%) becoming colonised; eighteen (79%) of these became colonised in hospital at a time that overlapped with the admission of a B cepacia positive child. Three different bacteriocin types were isolated, with one type (S22/PO) being present in 17 (74%) patients. The outcome for children who became colonised with B cepacia was compared with that in 33 children who continued to be colonised with Pseudomonas aeruginosa alone. RESULTS--Children colonised with B cepacia were older and more poorly nourished than those colonised with P aeruginosa, but did not have poorer pulmonary function. After colonisation, the forced expiratory volume in one second (FEV1) deteriorated between consecutive annual tests, with the average deterioration being greater in those with higher initial levels. Five children with B cepacia died from respiratory failure although none showed a fulminant deterioration. Introduction of segregation measures within hospital led to a dramatic decrease in the number of newly colonised patients. CONCLUSIONS--This study provides further evidence for person-to-person spread of B cepacia and confirms the effectiveness of simple isolation measures in interrupting spread. Colonisation with B cepacia and P aeruginosa in children is associated with a more rapid decline in lung function and a significantly increased mortality compared with cases colonised with P aeruginosa alone.
Shiga toxin-producing Escherichia coli (STEC) strains are a diverse group of organisms which are known to cause diarrhea and hemorrhagic colitis in humans. We have recently described a large food-borne outbreak of STEC disease caused by contaminated semidry fermented sausage (A. W. Paton, R. Ratcliff, R. M. Doyle, J. Seymour-Murray, D. Davos, J. A. Lanser, and J. C. Paton, J. Clin. Microbiol. 34:1622-1627, 1996). STEC strains belonging to several O serotypes were isolated from the contaminated food source, but of these, only a subset were isolated from patients with diarrhea or hemolytic-uremic syndrome (HUS). In the present study, we characterized these STEC isolates with respect to the presence of putative virulence-associated genes and the capacity to adhere to a human intestinal epithelial cell line (Henle 407). The O111:H- STEC strain 95NR1 (isolated from one of the outbreak HUS patients) was shown to adhere to Henle 407 cells in a dose-dependent, mannose-resistant fashion. Microscopic examination revealed a diffuse pattern of adherence for this as well as several other STEC strains. Interestingly, the adherence of STEC strains from HUS cases (both outbreak related and sporadic) was significantly greater than that of STEC strains found in the contaminated food source but not found in any patients. These studies support the hypothesis that an enhanced capacity to adhere to intestinal cells is one of the factors which distinguishes human-virulent STEC strains from those of lesser clinical significance.
We have previously reported the nucleotide sequence of the Streptococcus pneumoniae type 19F capsular polysaccharide synthesis locus (cps19f), which consists of 15 open reading frames (ORFs) designated cps19fA to -O. Hybridization analysis indicated that close homologs for cps19fA to -H and cps19fK to -O were found in type 19B, but there were no homologs for cps19fI and -J. In this study we used long-range PCR to amplify and clone a 10.5-kb section of the S. pneumoniae type 19B capsule locus (cps19b) between cps19bH and cps19bK. This region of the cps19b locus is 4 kb larger than that in the cps19f locus and replaces cps19fI and cps19fJ with five new ORFs, designated cps19bP, -I, -Q, -R, and -J. We have proposed functions for four of the protein products, including functional homologs of Cps19fI and Cps19fJ. Transformation of a S. pneumoniae mutant containing an interrupted type 19F capsule locus with the 10.5-kb cps19b PCR product converted the recipient strain to type 19B. Southern hybridization analysis indicated that cps19bP, -I, -Q, -R, and -J are unique to type 19B and the closely related type 19C.
We observed that differences in the in vivo growth kinetics of pneumococcal strains of capsular types 3, 4, 5, and 6 were reminiscent of differences that we had previously reported for type 2 strain D39 and its pneumolysin-deficient mutant, PLN. Capsular type 2 Streptococcus pneumoniae D39 exhibits exponential growth in the blood of XID mice until the death of the mice at 24 to 36 h. In contrast, PLN reaches a plateau in growth that is maintained for several days. Capsular type 3 and 5 strains exhibited exponential growth and caused rapid death of XID mice following intravenous challenge, similar to the observation with D39. Strains of capsular types 4 and 6 exhibited growth kinetics reminiscent of PLN. Since the observed differences in the pathogenesis of types 3 and 5 compared to 4 and 6 were reminiscent of the effects of pneumolysin deficiency in type 2, we examined the levels of in vitro pneumolysin production for the entire panel of strains. The onset of pneumolysin production in most strains was rapid and occurred near the end of log-phase growth. Differences in in vivo growth patterns of capsular type 2, 3, 4, 5, and 6 strains were not found to be associated with differences in the levels of pneumolysin.