Cognitive symptoms are associated with functional disability in Huntington disease; yet, few controlled trials have examined cognitive treatments that could improve patient independence and quality of life. Atomoxetine is a norepinephrine reuptake inhibitor approved for treatment of attention-deficit/hyperactivity disorder.
Twenty participants with mild Huntington disease who complained of inattention were randomized to receive atomoxetine (80 mg/d) or placebo in a 10-week double-blind crossover study. Primary outcome measures were self-reported attention and attention and executive neuropsychological composite scores. Secondary outcomes were psychiatric and motor symptom scores.
The rate of reported adverse effects while on atomoxetine was 56% (vs 35% on placebo), which most commonly included dry mouth (39%), loss of appetite (22%), insomnia (22%), and dizziness (17%). There were no serious adverse events related to atomoxetine. There were statistically significant, although mild, increases in heart rate and diastolic blood pressure on atomoxetine, consistent with other studies and not requiring medical referral. There were no significant improvements while on atomoxetine compared with placebo on primary outcomes. However, there was evidence of significant placebo effects on self-reported attention and psychiatric functions. There were no group differences on the Unified Huntington's Disease Rating total motor score.
Atomoxetine demonstrated no advantages over placebo for primary or secondary outcomes. Although atomoxetine was not effective at improving attention at this dose, its safety and tolerability were similar to other studies.
Huntington disease; randomized controlled trial; neuropsychological assessment; clinical trials
BACKGROUND AND PURPOSE
Excess morbidity/mortality in rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease. In this ‘proof-of-concept’ study, vascular function was characterized in the murine collagen-induced arthritis (mCIA) model, the benchmark choice for evaluation of the pathological processes and assessment of new therapies.
Mice in the very early stages of arthritis development [and appropriate naïve (non-immunized) age-matched controls] were used in the study. Blood pressure was measured using tail cuff plethysmography. Vascular function in rings of isolated aorta was studied with isometric tension myography. Levels of NO metabolites (NOx), MMP-9 protein and IL-1β in plasma and MMP-9 protein in aortic homogenates were quantified.
Impaired vascular contractile responses in arthritis were unaffected by ex vivo inhibition of NOS (endothelial/neuronal and inducible) or COX activities. Endothelium-dependent and -independent relaxation, plasma NOx and blood pressure were unaffected by arthritis. Plasma and aortic homogenate MMP-9 protein levels were increased significantly in arthritis. Incubation of aortic tissues from naïve control animals with exogenous MMP-9 impaired subsequent contractile responses, mirroring that observed in arthritis. A role for IL-1β in perpetuating contractile dysfunction and increasing aortic MMP-9 was excluded.
CONCLUSIONS AND IMPLICATIONS
These data identify for the first time a relationship between early arthritis and contractile dysfunction and a possible role for MMP-9 therein, in the absence of overt endothelial dysfunction or increased NO production. As such, MMP-9 may constitute a significant target for early intervention in RA patients with a view to decreasing risk of cardiovascular disease.
arthritis; cardiovascular disease; aorta: contractile dysfunction; matrix metalloproteinase 9
Osteoarthritis (OA) of the knee is a major cause of pain and limited function in older adults. Longer-term studies of medical therapy of OA are uncommon. This study was undertaken to evaluate the efficacy and safety of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 24 months.
A 24-month, double-blind, placebo controlled study, conducted at 9 sites in the United States ancillary to the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/ Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients who had been randomized to 1 of the 5 groups in GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome measure was the number who reached a 20% reduction in WOMAC pain over 24 months. Secondary outcomes included reaching an OMERACT/OARSI response and change from baseline in WOMAC pain and function.
The odds of achieving a 20%WOMAC were 1.21 for celecoxib, 1.16 for glucosamine, 0.83 for glucosamine and chondroitin sulfate and 0.69 for chondroitin sulfate alone with widely overlapping confidence intervals for all treatments.
Over 2 years, no treatment achieved a clinically important difference in WOMAC Pain or Function as compared with placebo. However, glucosamine and celecoxib showed beneficial trends. Adverse reactions were not meaningfully different among treatment groups and serious adverse events were rare for all therapies.
Osteoarthritis; nutraceutical; coxib; adverse events; efficacy
We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 SNPs mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with p<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at p<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the US/Australia, Germany, China, Japan, Israel and Sweden (n= 5142 cases/ 6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), p=0.0009). The SNP maps 85kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.
FGFR2; schizophrenia; Genome Wide Association Study
To determine whether a longitudinal, case-based evaluation system can predict acquisition of competency in surgical pathology and how trainees at risk can be identified early.
Data were collected for trainee performance on surgical pathology cases (how well their diagnosis agreed with the faculty diagnosis) and compared with training outcomes. Negative training outcomes included failure to complete the residency, failure to pass the anatomic pathology component of the American Board of Pathology examination, and/or failure to obtain or hold a position immediately following training.
Thirty-three trainees recorded diagnoses for 54 326 surgical pathology cases, with outcome data available for 15 residents. Mean case-based performance was significantly higher for those with positive outcomes, and outcome status could be predicted as early as postgraduate year-1 (P = .0001). Performance on the first postgraduate year-1 rotation was significantly associated with the outcome (P = .02). Although trainees with unsuccessful outcomes improved their performance more rapidly, they started below residents with successful outcomes and did not make up the difference during training. There was no significant difference in Step 1 or 2 United States Medical Licensing Examination (USMLE) scores when compared with performance or final outcomes (P = .43 and P = .68, respectively) and the resident in-service examination (RISE) had limited predictive ability.
Differences between successful- and unsuccessful-outcome residents were most evident in early residency, ideal for designing interventions or counseling residents to consider another specialty.
Our longitudinal case-based system successfully identified trainees at risk for failure to acquire critical competencies for surgical pathology early in the program.
Mycobacterium tuberculosis has 10 universal stress proteins, whose function is unknown. However, proteomic and transcriptomic analyses have shown that a number of usp genes are significantly upregulated under hypoxic conditions and in response to nitric oxide and carbon monoxide, as well as during M. tuberculosis infection of macrophage cell lines. Six of these USPs are part of the DosR regulon and this, along with their expression pattern and the phenotypes of usp mutants in other bacterial species, suggests a potential role in the persistence and/or intracellular survival of Mtb. Knock-out mutants of individual usp genes encoding the USPs Rv1996, Rv2005c, Rv2026c and Rv2028c were generated and their growth and survival under hypoxic and other stress conditions examined. Although the majority of usp genes are highly induced in hypoxic conditions, mutation did not affect the long term survival of Mtb under these conditions, or in response to a range of stress conditions chosen to represent the environmental onslaughts experienced by the bacillus during an infection, nor during infection of mouse and human – derived macrophage cell lines. The possibility remains that these USPs are functionally redundant in Mtb.
DosR; Hypoxia; Stationary phase; hspX
Osteoarthritis of the knee causes significant morbidity and current medical treatment is limited to symptom relief, as therapies able to slow structural damage remain elusive. This study sought to evaluate the effect of glucosamine hydrochloride (glucosamine, G), sodium chondroitin sulfate (chondroitin sulfate, CS) (alone and in combination), celecoxib and placebo on progressive loss of joint space width (JSW).
A double-blind twenty-four month placebo-controlled study conducted at nine sites in the United States enrolled 572 participants from Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) who satisfied radiographic criteria (Kellgren and Lawrence (K&L) Grade 2 or 3 changes and JSW of at least 2mm at baseline). Persons with primarily lateral compartment narrowing at any time point were excluded. Patients continued G 500mg three times daily, CS 400mg three times daily, the combination, celecoxib 200mg daily or placebo as randomized for GAIT. Minimum medial tibiofemoral JSW was measured at baseline, 12 and 24 months. The primary outcome measure was JSW change from baseline.
The average JSW loss at 2 years for placebo, adjusted for design and clinical factors, was 0.16mm. No statistically significant difference for any treatment group compared to the placebo group was observed. Treatment effects for K&L Grade 2 knees, but not K&L Grade 3 knees showed a trend toward improvement relative to placebo. The study’s power was diminished by sample size, variance of JSW measurement and a smaller than expected loss in JSW.
At two years, no treatment achieved a predefined clinically important difference in JSW loss compared to placebo. However, patients with K&L Grade 2 osteoarthritis appear to have the greatest potential for modification by these treatments (ClinicalTrials.gov number, NCT00032890).
Congenital constriction band syndrome is a sporadic condition that may also be present in association with other congenital anomalies. It has an incidence varying from one in 1200 to one in 15,000 live births. There is a significant predilection for the upper extremities and distal limbs. The two main objectives for the treatment of congenital constriction band syndrome are improvement of function and improvement of cosmetic appearance. Different surgical techniques, such as Z-plasty, have been described and used for decades; however, direct closure after the excision of the constricting band seems to be the simplest and most appropriate, allowing the fatty tissue to naturally reposition itself under the skin. This technique is used in a two-stage approach to avoid affecting distal circulation to the limb.
Amniotic bands; Congenital constriction band syndrome; Direct closure; Z-plasty
Self-healing via a vascular network is an active research topic, with several recent publications reporting the application and optimization of these systems. This work represents the first consideration of the probable failure modes of a self-healing system as a driver for network design. The critical failure modes of a proposed self-healing system based on a vascular network were identified via a failure modes, effects and criticality analysis and compared to those of the human circulatory system. A range of engineering and biomimetic design concepts to address these critical failure modes is suggested with minimum system mass the overall design driver for high-performance systems. Plant vasculature has been mimicked to propose a segregated network to address the risk of fluid leakage. This approach could allow a network to be segregated into six separate paths with a system mass penalty of only approximately 25%. Fluid flow interconnections that mimic the anastomoses of animal vasculatures can be used within a segregated network to balance the risk of failure by leakage and blockage. These biomimetic approaches define a design space that considers the existing published literature in the context of system reliability.
self-repair; branched network; polymer composite; human circulation
Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression.
We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers).
Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83).
Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.
schizophrenia; depression; linkage; covariate; chromosome 4q
To examine functional outcomes from a rehabilitation programme and to compare two methods for evaluating cost efficiency of rehabilitation in patients with severe complex disability.
Subjects and setting
Two hundred and ninety seven consecutive admissions to a specialist inpatient rehabilitation unit following severe acquired brain injury.
Retrospective analysis of routinely collected data, including the Functional Independence Measure (FIM), Barthel Index, and Northwick Park Dependency Score and Care Needs Assessment (NPDS/NPCNA), which provides a generic estimation of dependency, care hours. and weekly cost of continuing care in the community. Patients were analysed in three groups according to dependency on admission: “low” (NPDS<10 (n = 83)); “medium” (NPDS10–24 (n = 112)); “high” (NPDS >24 (n = 102)).
Mean length of stay (LOS) 112 (SD 66) days. All groups showed significant reduction in dependency between admission and discharge on all measures (paired t tests: p<0.001). Mean reduction in “weekly cost of care” was greatest in the high dependency group at £639 per week (95% CI 488 to 789)), as compared with the medium (£323/week (95% CI 217 to 428)), and low (£111/week (95% CI 42 to 179)) dependency groups. Despite their longer LOS, time taken to offset the initial cost of rehabilitation was only 16.3 months in the high dependency group, compared with 21.5 months (medium dependency) and 38.8 months (low dependency). FIM efficiency (FIM gain/LOS) appeared greatest in the medium dependency group (0.25), compared with the low (0.17) and high (0.16) dependency groups.
The NPDS/NPCNA detected changes in dependency potentially associated with substantial savings in the cost of ongoing care, especially in high dependency patients. Floor effects in responsiveness of the FIM may lead to underestimation of efficiency of rehabilitation in higher dependency patients.
rehabilitation; outcome measurement; dependency; cost efficiency; brain injury
Intervention development research is an essential prerequisite of any study that attempts to determine whether specific interventions work to prevent work related injury and illness.
Focus groups (n = 5) and direct observational studies (n = 21) of printers were used to elicit key issues that would aid the development of subsequent interventions. Transcripts from these were analysed by standard qualitative methods to identify common and related themes.
The views of managers differed significantly from those of print workers in a number of areas, and working practices did not always follow policy. The majority of printers did not perceive dermatitis to be a major problem, although many complained of dry hands. Other key results included: the lack of skin care policy in most companies; poor understanding of the nature, causes, and treatment of dermatitis; low priority of dermatitis within health and safety concerns; little or no provision of occupational health services, particularly skin checks; variability in provision of and access to appropriate skin protection; and lack of accessible washing facilities.
As a result it was decided to evaluate the implementation of four interventions: provision of (1) skin checks and treatment advice; (2) gloves of the correct type and size, and use of an after‐work cream; (3) information on dermatitis within the printing industry; and (4) development of best practice skin care policy.
intervention development; occupational research; occupational contact dermatitis; printing
Mandibular fractures can lead to significant functional and aesthetic sequelae if treated improperly. They may act as an indicator of concomitant trauma and are very demanding on the public health care system. Thus, knowledge of mandibular fracture epidemiology is critical to effective prevention, as well the establishment of accurate trauma evaluation protocols.
To identify the epidemiology of mandibular fractures treated at a level 1 Canadian trauma centre, clarify the pathogenesis of these epidemiological patterns and suggest potential targets for preventive efforts.
A retrospective review of all mandibular fracture patients presenting to the Montreal General Hospital between 1998 and 2003 was performed. Medical records and digitized radiographic imaging were used to collect patient demographics and injury data.
The chart review identified 181 patients with 307 mandibular fractures. Fifty-two per cent of the fractures occurred in individuals 21 to 40 years of age, 78% of patients were male, and there was wide ethnic diversity. Sixty percent of patients had multiple mandibular fractures; 29% were symphyseal/parasymphyseal fractures, 25% were condylar fractures and 23% were angle fractures. Assault was the most common mechanism of injury, with 29% of fractures involving alcohol or illegal drug use. Thirty percent of patients had an associated facial fracture, and more than one-third had another major injury.
The present epidemiological review reveals several potential prevention targets as well as significant trends. Further research into the impact of these preventive measures could more objectively identify their impact on mandibular trauma.
Epidemiology; Facial trauma; Mandible fracture; Prevention
Foreign body ingestion is a common occurrence in childhood. We report the outcome of an infant who swallowed a piece of glass. The absence of a foreign body on chest radiograph led to delayed diagnosis and then to the well documented complications of retropharyngeal abscess and mediastinitis. She was admitted to the paediatric intensive care unit a week after her initial presentation, subjected to multiple invasive and non‐invasive procedures, and 6 weeks after her initial presentation to the accident and emergency department, was discharged back to her referring hospital having re‐established oral feeds.
x ray; foreign body
A biomimetic analysis is presented in which an expression for the optimum vessel diameter for the design of minimum mass branching or vascular networks in engineering applications is derived. Agreement with constructal theory is shown. A simple design case is illustrated and application to more complex cases with branching networks of several generations discussed. The analysis is also extended into the turbulent flow regime, giving an optimization tool with considerable utility in the design of fluid distribution systems. The distribution of vessel lengths in different generations was also found to be a useful design variable. Integrating a network into a structure is also discussed. Where it is necessary to adopt a non-optimum vessel diameter for structural integration, it has been shown that small deviations from the minimum mass optimum can be tolerated, but large variations could be expected to produce a punitive and rapidly increasing mass penalty.
vascular flow; biomimetic; sandwich structures; self-healing; constructal theory
xanthogranuloma; lacrimal gland; Erdheim-Chester disease; adult onset asthma
Silver dressings are a proven method for burn treatment. Current challenges associated with burn treatment include pain management and limited hospital resources. A new silver-coated nylon dressing was used at the Montreal Children’s Hospital (Montreal, Quebec) to help reduce traumatic dressing changes and cost.
Burn victims in a pediatric patient population were followed over two years. Patients were excluded if they were evaluated more than 48 h postburn or if the burn affected less than 5% of the total body surface area. The same burn team admitted and treated all case subjects, and one dressing nurse recorded and monitored all progress throughout the study to ensure standardization.
Fifteen patients were included in the study. The average number of dressing changes needed was 4.13, with a median of three changes. The average total body surface area burned was 8%, with a mean of 13.9 days before superficial wounds were re-epithelialized. The average length of in-hospital stay was four days. The cost was $388 less for silver-coated nylon dressings than for silver sulfadiazine cream for seven days of treatment. Silver-coated nylon dressings did not leave any residue or pseudoeschar on the wounds and were easily maintained at home.
The silver-coated nylon dressings are as effective as other silver dressings used for pediatric burn victims. The dressings are less traumatic, require fewer resources and do not leave wound residue compared with other dressings.
Burn; Plastic surgery; Prospective study; Silver; SilverLeaf; Sulfadiazine; treatment
Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case–control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants, were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and α1-globulin, α2-globulin, β-globulin, γ-globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51–6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation.
Objective: To establish the prevalence of and risk factors for Chlamydia trachomatis infection to determine the role of universal versus targeted testing.
Methods: A prospective study of 1107 women attending two sexual and reproductive health clinics in Melbourne, Australia, was carried out. A questionnaire was used to establish risk factors. Urine samples were tested for C trachomatis by PCR. The main outcome measures were prevalence of and risk factors for C trachomatis infection.
Results: Of 1107 recruitable women, 851 (76.9%) consented and were successfully tested. C trachomatis was detected in 18 (4.8% (95% CI 2.9 to 7.5)) of 373 women in the inner city and eight (1.7% (95% CI (0.7 to 3.3)) of 478 women in the suburban clinic. Of women under 25 years, 17 (6.2% (95% CI 3.7 to 9.8)) of 273 in the inner city in contrast with three (1.7% (95% CI 0.4 to 5.0)) of 174 in the suburban clinic were infected. In the inner city clinic, age under 25 years (OR 5.4 (95% CI 0.7 to 41.5)), vaginal discharge (OR 4.1 (95% CI 1.5 to 11.1)), and recent change of sexual partner (OR 4.6 (95% CI 1.6 to 12.9)) were associated with C trachomatis. In contrast, in the suburban clinic, only vaginal discharge (OR 3.5 (95% CI 0.9 to 14.3)) and recent change of sexual partner (OR 3.4 (95% CI 0.8 to 15.7)) were identified as risk factors. Multivariate analysis showed that recent change of partner (OR 4.5 (95% CI 1.5 to 13.8)) was the most strongly associated independent risk factor for infection in the inner city clinic.
Conclusion: The high prevalence of C trachomatis indicates that universal testing should be undertaken in the inner city clinic. Young age may not be a risk factor for C trachomatis in more affluent populations with lower prevalence rates. No risk factors were identified with sufficient sensitivity and specificity to be useful for targeted testing. Prevalence and identifiable risk factors for C trachomatis are not transferable between populations, even in the same city.
Aims: To quantify occupational ill health resulting from dermatitis in the UK printing industry and to explore links with particular processes and activities.
Methods: Approximately 2600 members of the Graphical, Paper and Media Union living in Nottinghamshire were sent a self completion questionnaire. A sample of respondents, both those who reported current skin problems and those who did not, were invited for a short dermatological examination.
Results: The overall response rate was 62%. A total of 1189 respondents were directly involved in the printing industry and categorised according to work in pre-press (25%), printing (46%), or finishing (42%) processes. A total of 490 respondents (41%) self reported having a skin complaint at some time. Prevalence was highest in males (43%) and those working in printing (49%), in particular those who cleaned rollers and cylinders or who came into contact with substances containing isocyanates on a daily basis. The most commonly affected areas reported were the fingers and webs between the fingers. Twenty six per cent of the 490 reported a current problem on the hand. Reported symptoms included itching (61%), rash (58%), and dry skin (56%). Although certain printing industry substances were thought by respondents to aggravate their condition, constant washing and friction was most often cited. Reported use of protective equipment and cleansing products was generally high, particularly by printers. Clinical examination confirmed the high self reported prevalence and also identified a substantial proportion of mild cases which were not reported. The overall prevalence of occupationally related skin complaints is estimated to be 40%.
Conclusions: A much higher prevalence of dermatitis has been identified than from routine surveillance schemes. The use of good quality records from unions with high membership facilitated access to workers across a range of company sites and printing processes. Validation of self reported symptoms through clinical examination was shown to be essential. The importance of non-chemical causes of dermatitis was highlighted. The findings point towards the need for the development of effective and acceptable risk reduction strategies, in particular to reduce water contact and friction.
BACKGROUND—A study was
undertaken to determine the consequences of long term intranasal
instillation of Penicillium
chrysogenum propagules in a mouse model.
mice were inoculated intranasally each week for six weeks with
104 viable and non-viable P
chrysogenum conidia. Cytokine levels and cellular responses
in these animals were then measured.
controls, mice inoculated intranasally each week for six weeks with
104P chrysogenum conidia
(average viability 25%) produced significantly more total serum IgE
(mean difference 1823.11, lower and upper 95% confidence intervals
(CI) 539.09 to 3107.13), peripheral eosinophils (mean difference 5.11, 95% CI 2.24 to 7.99), and airway eosinophilia (rank difference 11.33, 95% CI 9.0 to 20.0). With the exception of airway neutrophilia (mean
difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intranasally
with 104 non-viable conidia did not show significant
changes in total serum IgE, peripheral or airway eosinophils. However,
when compared with controls, this group (104 non-viable)
had a significant increase in total serum IgG2a (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-γ (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice
inoculated intranasally with 104 viable
P chrysogenum conidia had
significantly increased levels of interleukin (IL)-4 (mean difference
285.28, 95% CI 108.73 to 461.82) and IL-5 (mean difference 16.61, 95%
CI 11.23 to 21.99). The IgG2a/IgE ratio and the
IFN-γ/IL-4 ratio was lower in the group of mice inoculated
intranasally with 104 viable conidia than in the
104 non-viable conidia group and the controls. When
proteins were extracted from P chrysogenum
conidia, attached to microtitre plates and incubated with serum from
the 104 viable group, significant increases in
conidia-specific IgE and IgG1 were observed compared with
controls, while serum from the 104 non-viable group was
similar to controls.
suggest that long term inhalation of viable P
chrysogenum propagules induces type 2 T helper cell mediated
(Th2) inflammatory responses such as increases in total and
conidia-specific serum IgE and IgG1, together with BAL
fluid levels of IL-4 and IL-5 and peripheral and airway
eosinophilia, which are mediators of allergic reactions.