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1.  Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort 
Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions.
Methodology/Principal Findings
TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100.
Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.
Author Summary
Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules.
PMCID: PMC3236729  PMID: 22180790
2.  The risk factors for unexplained antepartum stillbirths in Scotland, 1994 to 2003 
Journal of Perinatology  2009;30(5):311-318.
To determine the factors contributing to unexplained antepartum stillbirth in Scotland.
Study Design:
A 10-year birth database in Scotland was used to compare the unexplained antepartum stillbirth with other birth outcomes. The sample unit was a pregnant mother with a gestational age of 20 weeks and above and with a fetal birth weight of 200 g and above.
Maternal age of 35 years and above, lower deprivation category, inaccessible area of residence, maternal smoking, maternal height of <160 cm and gestational age of above 39 weeks were significantly associated with unexplained antepartum stillbirth. In multivariable analysis only maternal age (adjusted odds ratio (OR): 1.8, confidence interval (CI): 1.1 to 3.0, P=0.02), smoking during pregnancy (adjusted OR: 2.0, CI: 1.1 to 3.5, P=0.02), and maternal height (adjusted OR: 1.4, CI: 1.1 to 1.8, P=0.01), remain significant. Screening of pregnancies based on these three risk factors had 4.2% sensitivity and 99.4% specificity. The prevalence of stillbirth for this population was 0.2%. A positive predictive value of only 1.2% implies that only 1 in 83 women with these three risk factors will have antepartum stillbirth. The remaining 82 will suffer needless anxiety and potentially diagnostic procedures.
Advanced maternal age, maternal smoking, and shorter maternal height were associated risk for unexplained antepartum stillbirth but screening based on these factors would be of limited value.
PMCID: PMC2864419  PMID: 19829298
singleton; nullipara; smoking; screening; maternal height; gestational age
3.  Variation in coronary risk factors by social status: results from the Scottish Heart Health Study. 
The relationship between social status and coronary heart disease in the United Kingdom is well established with the more socially disadvantaged being at higher risk. There is also evidence that the levels of most of the known coronary risk factors vary with social status in a way consistent with their relationship to coronary heart disease. Using data from the Scottish heart health study the aim of this study was to quantify, for men and women, the variation in four of the main coronary heart disease risk factors--smoking, serum total cholesterol level, blood pressure and obesity--according to a number of social factors--occupational social class, housing tenure, level of education and employment status. The analyses used both mean risk factor levels as well as the percentages above suggested cut off levels, in order to provide estimates of the percentage of people at risk. All the risk factors, apart from total cholesterol level in men, showed fairly consistent variation across social groups with the more socially disadvantaged being at higher risk. Similar social variation was found for the percentages above the cut off levels, and these indicate that nearly 60% of the Scottish population aged 40-59 years, have one or more risk factors for coronary heart disease. These results suggest that some targeting of health education and management is appropriate, and this is especially relevant as the reforms to the National Health Service set health targets for health authorities and encourage general practitioners to provide health promotion services.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1372229  PMID: 1466917
4.  Cigarette tar content and symptoms of chronic bronchitis: results of the Scottish Heart Health Study. 
STUDY OBJECTIVE--The aim was to determine if there was a relationship between cigarette tar yield and rates of chronic cough and chronic phlegm. SETTING--22 districts across Scotland were used for the Scottish Heart Health Study (SHHS) which was conducted between 1984 and 1986 and from which the data for this analysis were obtained. SUBJECTS--10,359 men and women aged 40-59 years were studied. Of these, 2801 current cigarette smokers whose brand of cigarette smoked was known were selected. MEASUREMENTS AND MAIN RESULTS--Data on self reported smoking habits and prevalence of chronic cough and chronic phlegm were obtained from the SHHS. Tar yield was divided into three groups: low (less than or equal to 12 mg/cigarette); middle (13-14 mg/cigarette); high (greater than or equal to 15 mg/cigarette). The average tar yield consumed per person was 13.2 mg/cigarette. Women in the middle and high tar groups had smoked for longer and had significantly higher breath carbon monoxide levels, serum thiocyanate levels, serum cotinine levels, and daily cigarette consumption than the women in the low tar group. This pattern was not seen in men for any of these five smoking variables. Rates of chronic cough and chronic phlegm were higher with higher tar yield of cigarettes smoked for women (low tar v high tar: p less than 0.001) but not for men. Daily cigarette consumption and the number of years of smoking were the most significant risk factors for chronic cough and chronic phlegm for both men and women. Tar was still a significant risk factor (p less than 0.05) for women after controlling for these two risk factors and social class. CONCLUSIONS--Both sexes show strong effects of daily cigarette consumption and years of smoking on respiratory symptoms; women show an additional effect of cigarette tar content while men do not. The spread of tar yield in both sexes was small but there were more women on low tar cigarettes and this may have enabled a weak effect of tar to be seen better in them. On the other hand, tar level in women was confounded with other factors. Statistical methods of controlling for this may not have removed this confounding completely.
PMCID: PMC1059462  PMID: 1795148
5.  Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study. 
British Heart Journal  1990;64(5):295-298.
Data from 10,359 men and women aged 40-59 years from 22 districts in the Scottish Heart Health Study were used to describe the prevalence rates of coronary heart disease in Scotland in 1984-1986 and their relation to the geographical variation in mortality in these districts. Prevalence was measured by previous history, Rose chest pain questionnaire, and the Minnesota code of a 12 lead resting electrocardiogram. The prevalence of coronary heart disease in Scotland was high compared with studies from other countries that used the same standardised methods. A history of angina was more common in men (5.5%) than in women (3.9%), though in response to the Rose questionnaire 8.5% of women and 6.3% of men reported chest pain. A history of myocardial infarction was three times more common in men than women, as was a Q/QS pattern on the electrocardiogram. There were significant correlations between the different measures of coronary prevalence. District measures of angina correlated well with mortality from coronary heart disease, and these correlations tended to be stronger in women than in men. There was no significant correlation between mortality from coronary heart disease and measures of myocardial infarction. The study provides data on the prevalence of coronary heart disease in men and women that are valuable for the planning of cardiological services.
PMCID: PMC1216805  PMID: 2245107
6.  Coronary heart disease and water hardness in Scotland--is there a relationship? 
Scotland has a mortality rate from coronary disease which is one of the highest in the world. There is also a considerable variation in this mortality rate within Scotland. Data on water hardness throughout Scotland have been collected from Regional Water Authorities to see whether variations in coronary mortality rates can be explained by variations in water hardness. Analysis demonstrates a much weaker negative association than has been demonstrated in studies in other countries. The geographical variation in coronary mortality rates in Scotland cannot be explained by variations in water hardness, and weak association between these in Scotland is discussed.
PMCID: PMC1052625  PMID: 3443816
7.  The impact of quitting smoking on symptoms of chronic bronchitis: results of the Scottish Heart Health Study. 
Thorax  1991;46(2):112-116.
Scotland has high rates of death from diseases of the respiratory system and high rates of smoking, especially among women. Data on self reported smoking and prevalence of chronic cough and chronic phlegm among 10,359 men and women aged 40-59 years were obtained from the Scottish Heart Health Study. Overall, current cigarette smokers had rates of chronic cough and chronic phlegm four to five times those of never smokers after standardisation for age (32.3% v 6.5% for men and 24% v 5.5% for women for chronic cough; 31% v 8.3% for men and 21% v 5.5% for women for chronic phlegm). Ex-smokers' symptom rates were a little above those of never smokers and were significant for chronic cough among women and chronic phlegm among men. Men had higher symptom rates than women and this was true for smokers, ex-smokers, and never smokers. The higher rates among men could not be explained by higher cotinine concentrations. Tests to detect "deceivers" among ex-smokers and never smokers using biochemical validation suggested that 87 (1.5%) respondents were in fact smoking; they were excluded from analyses. There were substantially lower rates of chronic cough and chronic phlegm within a year of stopping smoking, and two to four years after stopping 89-99% of the difference between current smokers and never smokers was accounted for (99% and 93% for men and women with chronic cough, 96% and 89% for men and women with chronic phlegm). Even 10 years after stopping, rates of symptoms among ex-smokers remained a little above those of never smokers (except for women with chronic phlegm), though these differences were not statistically significant. Former heavy smokers continued to have rates of chronic cough and chronic phlegm that were higher than those of former light and moderate smokers (though not significantly so). These are cross sectional data, but they emphasise the importance for chronic bronchitis symptoms of giving up cigarette smoking, though the amount previously smoked continues to exert a small influence.
PMCID: PMC462964  PMID: 2014491
8.  Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. 
British Heart Journal  1990;64(3):199-203.
A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland.
PMCID: PMC1024372  PMID: 2206712
10.  Control of blood pressure in Scotland: the rule of halves. 
BMJ : British Medical Journal  1990;300(6730):981-983.
OBJECTIVE--Audit of detection, treatment, and control of hypertension in adults in Scotland. DESIGN--Cross sectional survey with random population sampling. SETTING--General practice centres in 22 Scottish districts. SUBJECTS--5123 Men and 5236 women aged 40-59 in the Scottish heart health study, randomly selected from 22 districts throughout Scotland, of whom 1262 men and 1061 women had hypertension (defined as receiving antihypertensive treatment or with blood pressure above defined cut off points). MAIN OUTCOME MEASURE--Hypertension (assessed by standardised recording, questionnaire on diagnosis, and antihypertensive drug treatment) according to criteria of the World Health Organisation (receiving antihypertensive treatment or blood pressure greater than or equal to 160/95 mm Hg, or both) and to modified criteria of the British Hypertension Society. RESULTS--In half the men with blood pressure greater than or equal to 160/95 mm Hg hypertension was undetected (670/1262, 53%), in half of those in whom it had been detected it was untreated (250/592, 42%), and in half of those receiving treatment it was not controlled (172/342, 50%). In women the numbers were: 486/1061, 46%; 188/575, 33%; and 155/387, 40% respectively. Assessment of blood pressure according to the British Hypertension Society's recommendations showed an improvement, but in only a quarter of men and 42% of women was hypertension detected and treated satisfactorily (142/561, 215/514 respectively). IMPLICATIONS--The detection and control of hypertension in Scotland is unsatisfactory, affecting management of this and other conditions, such as high blood cholesterol concentration, whose measurement is opportunistic and selective and depends on recognition of other risk factors.
PMCID: PMC1662684  PMID: 2344507
11.  Urinary electrolyte excretion, alcohol consumption, and blood pressure in the Scottish heart health study. 
BMJ : British Medical Journal  1988;297(6644):329-330.
As part of a study of risk factors for coronary heart disease 24 hour urine collections were obtained from 7354 men and women aged 40-59 selected at random from 22 districts throughout Scotland (Scottish heart health study). The mean of two standardised measurements of blood pressure was related to the reported consumption of alcohol and measurements of height, weight, pulse rate, and electrolyte excretion. Several significant correlations were found with both systolic and diastolic pressure, but only the coefficients for age, body mass index, and pulse rate were greater than 0.1. Alcohol consumption showed a weak positive correlation with blood pressure in men. Sodium excretion showed a weak positive correlation with blood pressure in both sexes, and potassium excretion showed weak negative correlations. In multiple regression analysis age, pulse rate, body mass index, alcohol consumption, and potassium excretion had significant independent effects but sodium excretion did not. Although measuring blood pressure twice on one occasion and 24 hour urinary sodium excretion only once may have weakened any potential correlation, the most likely explantation of these results is that the relation between sodium and blood pressure in the population is weak and that potassium and alcohol are of greater importance.
PMCID: PMC1834048  PMID: 3416163
13.  Comparison of response rates to a postal questionnaire from a general practice and a research unit. 
A postal questionnaire study was carried out in an urban general practice to determine the effect of the introductory letter being sent by the participants' own general practitioner compared with that from a letter sent directly from a research unit. By sequential sampling 409 individuals aged between 40 and 59 were assigned to one of two groups. The people in one group were written to by their own general practitioner and those in the other by a doctor from a research unit. Husbands and wives were paired and were always sent the same letter. A second letter was sent to nonresponders after one month. The response rate to the general practitioner was significantly higher than that to the doctor in the research unit (85% compared with 75%) and differed by age and sex. The results have important implications for other research workers and suggest that general practitioners are in a key position in the conduct of medical and epidemiological research.
PMCID: PMC1418119  PMID: 3933719
16.  Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome 
British Journal of Cancer  2005;92(2):225-230.
Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7–12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery.
PMCID: PMC2361843  PMID: 15655557
breast cancer; mastectomy; post mastectomy pain; chronic pain
17.  Assessment of the immunization status of practice children under five years of age 
Many professional groups are involved in immunization, and four different immunization records may be kept—the general practice record, the community child health record, the health visitor record and a record retained by the parent. The first three of these sources were examined for the immunization status of children under five years of age in a practice. The health visitor record was the most comprehensive. There was a remarkable improvement in pertussis vaccine acceptance over the four years reviewed but there were gaps in the uptake of measles vaccine.
PMCID: PMC1959619  PMID: 6708006
18.  Developmental genetics in primitive chordates. 
Recent advances in the study of the genetics and genomics of urochordates testify to a renewed interest in this chordate subphylum, believed to be the most primitive extant chordate relatives of the vertebrates. In addition to their primitive nature, many features of their reproduction and early development make the urochordates ideal model chordates for developmental genetics. Many urochordates spawn large numbers of transparent and externally developing embryos on a daily basis. Additionally, the embryos have a defined and well-characterized cell lineage until the end of gastrulation. Furthermore, the genomes of the urochordates have been estimated to be only 5-10% of the size of the vertebrates and to have fewer genes and less genetic redundancy than vertebrates. Genetic screens, which are powerful tools for investigating developmental mechanisms, have recently become feasible due to new culturing techniques in ascidians. Because hermaphrodite ascidians are able to self-fertilize, recessive mutations can be detected in a single generation. Several recent studies have demonstrated the feasibility of applying modern genetic techniques to the study of ascidian biology.
PMCID: PMC1088537  PMID: 11604124
19.  Differential effects of the incorporation of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) on the binding of the transcription factors, AP-1 and TFIID, to their cognate target DNA sequences. 
Nucleic Acids Research  1996;24(21):4111-4116.
The thymidine analog, 1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl)-5-iodouracil (FIAU), is incorporated into DNA in cell culture and in vivo. To investigate the effect of incorporation of FIAU into DNA on the binding of transcription factors, oligonucleotide duplexes which bind specifically to activator protein 1 (AP-1) or to TFIID were synthesized and binding of these oligonucleotides to their respective proteins was studied using gel-shift analysis. When thymidine at position -3, -1, 1 or 7 (relative to the first thymidine of the core binding sequence) was replaced with FIAU, binding to AP-1 was approximately 82, 28, 86 and 51%, respectively, of the binding to the non-substituted oligonucleotide to AP-1. When thymidine at position 3 or 5 (each adjacent to the center of dyad symmetry) was replaced with FIAU, binding to AP-1 was abrogated. Oligonucleotides containing FIAU at positions -1, 3 or 5, were much less able to compete with radiolabeled wild-type oligonucleotides for binding to AP-1. In contrast, the presence of FIAU, depending on its location, resulted in the increased binding of TFIID to its consensus target DNA sequence. These results indicate that incorporation of FIAU into DNA may induce local conformational changes resulting in the altered ability of transcriptional factors to bind to their cognate DNA sequences. Additional studies demonstrated that the presence of FIAU at a position 5' to the cleavage site in the consensus sequence T*TAA (where * is the cleavage site) inhibited restriction of the oligomeric duplex by MseI.
PMCID: PMC146219  PMID: 8932359
20.  Unemployment, socioenvironmental factors, and coronary heart disease in Scotland. 
British Heart Journal  1989;61(2):172-177.
Scotland, which has one of the highest death rates in the world from coronary heart disease, also has considerable regional variation in mortality from this cause. The relation between standardised mortality ratios for coronary deaths (1979-83) for 56 local government districts and a range of socioeconomic factors from the 1981 Census as well as climatic factors and water hardness were investigated. Strong associations were seen with several measures of social disadvantage, the strongest being with percentage of male unemployment. A fitted multiple regression model with mortality from coronary heart disease in men found independent effects of two social variables (percentage male unemployment and percentage social class III-V) and one climatic factor (rainfall). The model explained much (73%) of the geographical variation in mortality from coronary heart disease, but part of the geographical pattern, in particular some of the east-west gradient in mortality, remained unexplained by it. Explanations for the geographical variation and the association with economic factors are currently being sought in terms of individual risk factors in a large screening study, the Scottish Heart Health Study.
PMCID: PMC1216636  PMID: 2923755
21.  Computed axial tomography of the porcine nasal cavity and a morphometric comparison of the nasal turbinates with other visualization techniques. 
A non-invasive imaging modality, computed tomography (CT), was used to visualize changes in nasal turbinates of anesthetized pigs over a 12-week observation period (pigs were 14 wk of age at study week 0). Normal, non-infected pigs were compared to pigs with mild challenge-induced atrophic rhinitis (AR) in order to detect subtle differences in morphology. To determine feasibility for time course studies in future experiments, morphometric quantitation at the level of the 2nd premolar (turbinate area ratio or TAR) in cross-section CT images at multiple timepoints was done. Additionally, at study termination, the TAR determined from CT images, magnetic resonance imaging (MRI), and wet tissue (WT), were compared to each other and to the standard subjective measure, visual scoring. There were no statistically significant differences between the control and AR groups at CT imaging dates of 0, 3, 6, 9, or 12 wk (P = 0.182). However, a statistically significant decrease in TAR measurements over time (P = 0.015) was observed in both groups, with lower mean values observed on Weeks 3 and 6 before rebounding to baseline values at study termination. At Week 12 (termination of the study), the TAR measurements derived from CT, MRI, and WT were not statistically different from one another (P = 0.220) and the treatment group-by-method interaction was not significant (P = 0.800). This provided evidence of equivalency of the techniques. Mean values for normal and infected groups were not significantly different based on either TAR imaging methods (P = 0.552) or visual scores (P = 0.088). Thus, the current study demonstrated that CT was an acceptable alternative imaging modality which could be used for quantitation of turbinate changes in snouts of live pigs to provide data comparable to tissue taken at necropsy. Computed tomographic imaging would allow non-invasive tracking of disease or treatment responses within individual animals over time. Morphometric analysis of the TAR was equivalent between the CT, MRI, and WT specimens.
PMCID: PMC1189496  PMID: 9798095
22.  The quantitation of turbinate atrophy in pigs to measure the severity of induced atrophic rhinitis. 
The two-fold purpose of this study was to establish a useful image analysis technique for quantitation of turbinate atrophy and to determine an optimum bacterial dose for inducing atrophic rhinitis (AR). Two morphometric analysis methods were compared to determine a turbinate area ratio (TAR) and a turbinate perimeter ratio (TPR); the ratios of turbinate area to total nostril area and of turbinate perimeter to total nostril perimeter, respectively. Our first image analysis method differed from Collins et al (1) in that we used direct image capture (digitalization) via a video camera and a Macintosh microcomputer, rather than photographs and a digitizer tablet. The tracing techniques were the same as those used by Collins et al. The second morphometric method was modified from the first by exclusion of dorsal turbinate when tracing the nostril area and directly tracing only the ventral turbinate to get a turbinate measurement without subtracting. Area and perimeter ratios, for both methods, were compared to conventional visual snout scores, ventral measurements, and to each other. The results of the two image analysis methods correlated well, both with each other and with the visual scores. Doses of Pasteurella multocida (Pm) at a constant level, and Bordetella bronchiseptica (Bb) at various concentrations, were administered to 36 Hampshire-Duroc F1 SPF pigs to determine the best dose and frequency for inducing AR. Although the dose selection may have been somewhat affected by the pre-existing presence of Bb, the optimal dose per naris in this study was 2 mL Bb at 10(7) cfu/mL combined with 2 mL Pm at 10(9) cfu/mL inoculum. The frequency of administration (1 x or 2 x) did not greatly affect results. Turbinate area ratio was the best tool for quantitating gross morphological turbinate changes associated with atrophic rhinitis in this study. Our simplified modification of Collins et al image analysis method (exclusion of dorsal turbinates and direct measurement of ventral turbinates) correlated well with visual scores, and, when compared to Collins et al method, required less data manipulation and labour.
PMCID: PMC1263817  PMID: 8785717

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