Making the match and breaking it: values, perceptions, and obstacles of trainees applying into physician-scientist training programs.

BACKGROUND: Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing threat. Among the barriers facing physician-scientists today is the game-like model of U.S. medical residency matching through the National Research Matching Program (NRPM), which applies several assumptions regarding the comparability of applicant qualifications, cohort size, and the institutional breadth of applicants' training needs. METHODS: The current report therefore summarizes the survey-based views and experiences of physician-scientist trainees obtained following the 2021-2022 application cycle for research-oriented residency programs, or physician-scientist training programs (PSTPs). From among this small cohort of applicants, we obtained survey-based feedback of 27 PSTP applicants across 17 U.S. medical universities, among whom 85% (23/27) matched into a PSTP. RESULTS: Among these PSTP applicants, 25/27 (93%) recognized "scientific community" as the most important feature of a postgraduate training program, with applicants identifying as female placing a higher value on the program's infrastructure of personal and/or family support. Most (18/27) respondents found "waiting for interviews" as the most stressful phase of their application cycle, and roughly half of all respondents encountered at least one NRMP policy violation through post-interview communication. Specifically, 93% (25/27) respondents were contacted by at least one PSTP following interviews, and 1/3 of them admitted to feeling pressured into sharing their ranking preferences. CONCLUSION: We highlight many previously unrecognized priorities among applicants to PSTPs, which include fostering community among its trainees and reinforcing structured mentoring. We uncover an inconsistency among PSTPs regarding the post-interview process, which represents an opportunity to better support applicants seeking to gauge programs according to their clinical, scientific, and academic interests as physician-scientists, while still adhering to NRMP policies.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

[Oncogeriatric assessment: The first step in personalizing cancer treatment in the elderly]. / L'évaluation oncogériatrique : la première étape de la personnalisation du traitement du cancer du sujet âgé.

With aging worldwide population and the high incidence of cancer in the population of people over 75 years old, there is a need for oncologists and geriatricians to strengthen their collaboration to improve elderly patients care. Complexity of cancer and aging issues must be considered simultaneously to establish a personalized care plan. Thus, the G8 is a screening tool that allows to identify patients who should benefit from a geriatric assessment, which is a key step in the management process. This specific evaluation offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status and has demonstrated its prognostic value in terms of choice of treatment but also in terms of patient survival. In nearly 20% of cases, the geriatric assessment leads to a change in the choice of treatment, and at one year the initial care plan is not carried out in a quarter of cases. The presence of malnutrition and functional impairment leading to dependence on basic activities of daily living had a significant impact on this change in therapeutic choice. Survival is not only impacted by malnutrition and functional impairment but also by the presence of severe comorbidities and thymic and neurocognitive impairment. The patient's choice must remain at the center of the elaboration of the care plan with the oncologists and geriatricians in order to propose the most appropriate treatment for his or her situation.

Knowledge, Attitudes, Practices and Zoonotic Risk Perception of Bovine Q Fever (Coxiella burnetii) among Cattle Farmers and Veterinary Personnel in Northern Regions of Cameroon.

A cross-sectional survey was conducted to investigate the knowledge, attitudes, practices and zoonotic risk perception of Q fever among 484 selected cattle farmers (438) and veterinary personnel (46) in three northern regions of Cameroon. Data collection was conducted using questionnaires and responses were recoded into binary scale. An ANOVA test was used to assess significant differences in mean knowledge, attitude, practice and zoonotic risk perception (KAPP) scores between regions, while Linear regression was done to explore the relationship between demographic characteristic and KAPP. Overall, surveyed had low mean scores for knowledge (0.02 ± 0.11), desirable attitude (0.30 ± 0.16), appropriate practice (0.43 ± 0.13) and negative perception of zoonotic risks (0.05 ± 0.11). The means knowledge, attitude, practice and risks perception scores of cattle farmers were lower than those of veterinary personnel. The nature of respondent was negatively associated to knowledge and risks perception, while regions were negatively correlated to attitude and practice. These results revealed significant knowledge gaps, low levels of desired attitudes, and high-risk behavioral practices. To improve awareness, control programs are needed to update knowledge on medical personnel and to prevent animal-to-human transmission.

Seroprevalence and Risks Factors Associated with Coxiella burnetii Infection in Slaughterhouse Zebu Cattle (Bos indicus) from Northern Regions of Cameroon.

A study was conducted to determine the seroprevalence and risks factors of Coxiella burnetii in zebu cattle from the northern regions of Cameroon. From a total of 2016 (1754 females and 262 males) sera sampled, 801, 762 and 453 were collected, respectively, from Adamawa, North and Far North, and screened for Coxiella burnetii using indirect enzyme-linked immunosorbent assay (iELISA). A total of 23.76% (479/2016) were serologically positive. The seroprevalence of Adamawa, North and Far North were 29.09% (233/801), 19.95% (152/762) and 20.75% (94/453); respectively. The seropositivity of male and female were 4.58% and 26.62%; respectively. Cattle from Adamawa region were more likely to have been exposed to C. burnetii than animals from Far North region (OR = 3.28; 95%CI: 1.13-7.85; p = 0.02). The Gudali breed was significantly more infected than Aku (OR =2.52; 95%CI: 1.06-5.99; p = 0.03), and animals aged of (6-9) years were 1.89 times more likely to have been infected to C. burnetii than young animals (p = 0.03). The seropositivity to this bacterium was significantly associated to pregnant cattle than non-pregnant (OR = 1.71; 95%CI: 1.01-2.90; p = 0.04). Female cattle were more likely to have been infected by C. burnetii than male and the rainy season were 1.66 more associated to this disease than dry season. The linear regression model indicated that C. burnetii seropositivity were positively correlated to the regions (0.09, CI: 0.04; 0.18; p = 0.007), age (0.01, CI: -0.01; 0.04; p = 0.02), sex (0.19, CI: 0.08-0.32, p = 0.001) and physiological status (0.11, CI: -0.04; 0.26; p = 0.006). This study revealed that C. burnetii infection is widespread among zebu cattle of Adamawa, North and Far North of Cameroon.

Presence of Maedi Visna virus (MVV)-proviral DNA in the genital tissues of naturally infected ewes.

Maedi Visna virus (MVV) causes progressive degenerative inflammatory disease in multiple organs including the lungs (pneumonia, 'maedi'), mammary gland, joints and nervous system (meningoencephalomyelitis, 'visna') in sheep. Maedi Visna Virus has been detected in macrophages of several tissues and epithelial cells in vivo: bone marrow, cells of the central nervous system, lung and bronchial tissues, milk epithelial cells recovered from milk samples and epithelial cells of mammary tissue. However, the presence of MVV in the genital tracts of naturally infected ewes has not previously been studied. The aim of this study was to use nested-PCR, targeting the gag gene, to determine whether genital tissues (ovaries, oviducts and uterus) from 83 ewes originating from various breeding herds in the South-East of France were positive for MVV-proviral DNA. Peripheral blood mononuclear cells (PBMC) tested positive for MVV-proviral DNA, using nested-PCR analysis, in 57.8% of ewes (48/83). The provirus was also identified in 47% (78/166) of the ovaries, 38.6% (64/166) of the oviducts and 45.8% (38/83) of the uteri sampled. These findings clearly demonstrate, for the first time, that tissue samples from the genital tract of ewes (ovary, oviduct and uterus) can be infected with MVV. This suggests that there is a risk of vertical and/or horizontal transmission of MVV during embryo transfer from embryos produced in vivo or in vitro.

Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease.

The outcome of patients with cirrhosis and chronic kidney disease treated with combined liver-kidney transplantation (CLKT) is not well known because most series of patients treated with CLKT include not only patients with cirrhosis but also patients with inherited diseases without cirrhosis. To evaluate to what extent the combined kidney transplantation impairs posttransplantation outcome compared to liver transplantation (LT) alone, the outcome of patients with cirrhosis and chronic kidney disease treated with CLKT (n = 20) was compared to that of a group of patients with cirrhosis without chronic kidney disease treated with LT alone matched by age, sex, year of transplantation and severity of cirrhosis (n = 60). The primary end point of the study was survival, and secondary end points were outcome of renal function and complications within 6 months of transplantation. Patients with CLKT had a higher incidence of bacterial infections and transfusion requirements compared to LT patients. The incidence of acute renal failure during the first 6 months was similar, yet the severity of renal failure was greater in patients with CLKT. Hospital and intensive care unit (ICU) stays were longer in the CLKT group. One- and three-year survival probabilities in patients treated with CLKT were 80 and 75% compared to 97 and 88%, respectively, in patients treated with LT. In conclusion, CLKT for patients with cirrhosis and chronic kidney disease is associated with a relatively high frequency of postoperative complications that moderately impairs short-term survival. However, 3-year survival of patients with cirrhosis treated with CLKT is excellent.

Rift Valley fever--a threat for Europe?

Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants, caused by a Phlebovirus (Bunyaviridae). It is widespread in Africa and has recently spread to Yemen and Saudi Arabia. RVF epidemics are more and more frequent in Africa and the Middle East, probably in relation with climatic changes (episodes of heavy rainfall in eastern and southern Africa), as well as intensified livestock trade. The probability of introduction and large-scale spread of RVF in Europe is very low, but localized RVF outbreaks may occur in humid areas with a large population of ruminants. Should this happen, human cases would probably occur in exposed individuals: farmers, veterinarians, slaughterhouse employees etc. Surveillance and diagnostic methods are available, but control tools are limited: vector control is difficult to implement, and vaccines are only available for ruminants, with either a limited efficacy (inactivated vaccines) or a residual pathogenic effect. The best strategy to protect Europe and the rest of the world against RVF is to develop more efficient surveillance and control tools and to implement coordinated regional monitoring and control programmes.

Genetic differences among Staphylococcus aureus isolates from dairy ruminant species: a single-dye DNA microarray approach.

Staphylococcus aureus is recognized worldwide as a major pathogen causing clinical or subclinical intramammary infections in lactating sheep, goats and cows. The present study was carried out to compare 65 S. aureus isolates mainly obtained from nasal carriage and subclinical mastitis in dairy sheep and 43 isolates obtained from subclinical mastitis from 22 goats and 21 cows. A DNA microarray, containing probes against 190 true or putative virulence factors, was used to detect the presence of the virulence genes. Their presence/absence was independently assessed by PCR for the genes of interest. Sheep isolates obtained from the nostrils or the udders did not show any significant tissue specific virulence factor. The dominant pulse-field electrophoresis profile (OV/OV'), associated with spa clonal complex spa-CC 1773, matched mainly with the agr group III and was only found in ovine and caprine isolates. This clone was more specifically characterized by the prevalence of the following virulence genes: lpl4, ssl6, bsaA1, bsaB, bsaP, SAV0812. Moreover, seven virulence-associated genes (lpl1, sel, sec, tst, lukF-PV-like component, lukM, SAV0876) were associated with isolates from small ruminants, while the egc cluster, fhuD1, abiF and SAV2496 with bovine isolates. This genomic study suggests the existence of lineage- and host-specific genes leading to the development of host-specific pathogenic traits of S. aureus isolates.

[Clinical presentation and performance of urine dipstick for diagnosis of urinary infection in geriatric population]. / Présentation clinique et performance de la bandelette urinaire pour le diagnostic d'infection urinaire en population gériatrique.

BACKGROUND: Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population. PATIENTS AND METHOD: We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population. RESULTS: Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P<0.05), and mean MMSE score was lower (P<0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %). CONCLUSION: For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

Lack of risk of transmission of caprine arthritis-encephalitis virus (CAEV) after an appropriate embryo transfer procedure.

The aim of this study was to demonstrate that embryo transfer can be used to produce CAEV-free kids from CAEV-infected biological mothers when appropriate procedure is implemented. Twenty-eight goats that had tested positive for CAEV using PCR on vaginal secretions were used as embryo donors. Embryos with intact-ZP were selected and washed 10 times; they were then frozen and used for transfer into CAEV-free recipient goats. Nineteen of the 49 recipient goats gave birth, producing a total of 23 kids. Three blood samples were taken from each recipient goat, 10 days before, during, and 10 days after parturition; these were tested for CAEV antibodies using ELISA and for CAEV proviral DNA using PCR. The mothers were then euthanized. Tissue samples were taken from the lungs, udder, and retromammary and prescapular lymph nodes. The kids were separated from their mothers at birth. Seven of them died. At 4 months of age, 16 kids were subjected to drug-induced immunosuppression. Blood samples were taken every month from birth to 4 months of age; samples were then taken on days 15, 21, and 28 after the start of the immunosuppressive treatment. The kids were then euthanized and tissue samples taken from the carpal synovial membrane, lung tissue, prescapular lymph nodes, inguinal and retromammary lymph nodes, and uterus. All samples from the 19 recipient goats and 23 kids were found to be negative for CAEV antibodies and/or CAEV proviral DNA. Under acute conditions for infection this study clearly demonstrates that embryo transfer can be safely used to produce CAEV-free neonates from infected CAEV donors.

[Topical anesthesia without the use of an anesthesiologist in adult outpatient cataract surgery: Assessment of selection criteria on consultation, report of 248 cases]. / L'anesthésie topique sans recours à un médecin anesthésiste dans la chirurgie de la cataracte ambulatoire de l'adulte : évaluation des critères de sélection en consultation, à propos de 248 cas.

INTRODUCTION: This work aims to evaluate selection criteria used during the cataract surgery scheduling visit, to choose whether or not there will be an anesthesiologist available during the surgery, depending upon the patient's comorbidities. MATERIALS AND METHODS: Retrospective study performed in 2016 in Angers university medical center. Two groups were established on the cataract surgery scheduling visit, based on patients' comorbidities and vital signs (blood pressure, heart rate). One group of patients were operated with topical anesthesia, with the anesthesia team, the other one only with blood pressure and heart rate monitoring, with, if needed, a written protocol of sedation or blood pressure control, which could be administrated by a circulating nurse. Those two groups were compared in terms of postoperative complications, intraoperative pain and postoperative visual acuity. RESULTS: 248 surgeries were performed on 185 individual patients, with 108 under stand-alone topical anesthesia, and 135 under anesthetist-monitored topical anesthesia. No significant difference was demonstrated between the two groups, in terms of complications, intraoperative pain or visual acuity outcomes. DISCUSSION: This study allows us to assess selection criteria used in our hospital to determine which patients can undergo cataract surgery under topical anesthesia without the anesthesia team. This procedure lowers organizational constraints while still insuring patient safety. Some patients still probably need an anesthesiologist present, such as those with an unstable disease or risk of agitation, in order to optimize the medications administered during surgery.

Decreased glucocorticoid receptor activity following glucocorticoid receptor antisense RNA gene fragment transfection.

Depression is often characterized by increased cortisol secretion caused by hyperactivity of the hypothalamic-pituitary-adrenal axis and by nonsuppression of cortisol secretion following dexamethasone administration. This hyperactivity of the hypothalamic-pituitary-adrenal axis could result from a reduced glucocorticoid receptor (GR) activity in neurons involved in its control. To investigate the effect of reduced neuronal GR levels, we have blocked cellular GR mRNA processing and/or translation by introduction of a complementary GR antisense RNA strand. Two cell lines were transfected with a reporter plasmid carrying the chloramphenicol acetyltransferase (CAT) gene under control of the mouse mammary tumor virus long terminal repeat (a glucocorticoid-inducible promoter). This gene construction permitted assay of the sensitivity of the cells to glucocorticoid hormones. Cells were also cotransfected with a plasmid containing 1,815 bp of GR cDNA inserted in the reverse orientation downstream from either a neurofilament gene promoter element or the Rous sarcoma virus promoter element. Northern (RNA) blot analysis demonstrated formation of GR antisense RNA strands. Measurement of the sensitivity of CAT activity to exogeneous dexamethasone showed that although dexamethasone increased CAT activity by as much as 13-fold in control incubations, expression of GR antisense RNA caused a 2- to 4-fold decrease in the CAT response to dexamethasone. Stable transfectants bearing the GR antisense gene fragment construction demonstrated a 50 to 70% decrease of functional GR levels compared with normal cells, as evidenced by a ligand-binding assay with the type II glucocorticoid receptor-specific ligand [3H]RU 28362. These results validate the use of antisense RNA to GR to decrease cellular response to glucocorticoids.

Prevalence and epidemiological features of ovine enzootic abortion in Lithuania.

The aim of performed study was to determine the level of enzootic abortion (EA) in sheep breeding farms in different districts of Lithuania, to determine differences in clinical signs and infection frequency between various age groups, and to evaluate the sensitivity and specificity of complement fixation test for antibodies detection and indirect immunofluorescence for antigen detection in sheep chlamydiosis. The clinical, serological and immunological tests in sheep farms were performed in 2004 and 2005. Comparing different age groups of sheep revealed that the lowest number of infected sheep was registered in animals younger than 18 months (23.1%, antibodies titre 3.191 log2, P<0.05) and highest in animals aged 18 to 24 months (53.8%, antibodies titre 4.224 log2, P<0.001). In sheep aged more than 3 years, titre of antibodies was significantly reduced. The majority of infected sheep which aborted (86.4%) was registered in 18-24 month age group. Furthermore, in sheep which aborted the infection level was 2.5-fold higher as compared to sheep which didn't abort. Analysis of smears from patological material by indirect FAT revealed that 54.5% of animals were positive to Chlamydophila abortus infection. The highest prevalence of chlamydia (66.7%) was registered in placentas of sheep which aborted.

Detection of ovine lentivirus in the cumulus cells, but not in the oocytes or follicular fluid, of naturally infected sheep.

The aim of this study was to examine the Maedi-Visna virus (MVV) infection status of oocytes, cumulus cells, and follicular fluid taken from 140 ewes from breeding flocks. MVV proviral-DNA and MVV RNA were detected using nested-PCR and RT-PCR MVV gene amplification, respectively in the gag gene. Nested-PCR analysis for MVV proviral-DNA was positive in peripheral blood mononuclear cells in 37.1% (52/140) of ewes and in 44.6% (125/280) of ovarian cortex samples. The examination of samples taken from ovarian follicles demonstrated that 8/280 batches of cumulus cells contained MVV proviral-DNA, whereas none of the 280 batches of oocytes taken from the same ovaries and whose cumulus cells has been removed, was found to be PCR positive. This was confirmed by RT-PCR analysis showing no MVV-viral RNA detection in all batches of oocytes without cumulus cells (0/280) and follicular fluid samples taken from the last 88 ovaries (0/88). The purity of the oocyte fraction and the efficacy of cumulus cell removal from oocytes was proved by absence of granulosa cell-specific mRNA in all batches of oocytes lacking the cumulus cells, using RT-PCR. This is the first demonstration that ewe cumulus cells harbor MVV genome and despite being in contact with these infected-cumulus cells, the oocytes and follicular fluid remain free from infection. In addition, the enzymatic and mechanical procedures we used to remove infected-cumulus cells surrounding the oocytes, are effective to generate MVV free-oocytes from MVV-infected ewes.

ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer.

UNLABELLED: ESSENTIALS: Cancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are associated with the occurrence of VTE in cancer. BACKGROUND: Patients with cancer are at high risk of venous thromboembolism (VTE). ADAMTS-13 regulates von Willebrand factor (VWF) activity, which plays a role in the development of cancer and in VTE. OBJECTIVES: The aim of this study was to search for an association between the levels of VWF and ADAMTS-13 and VTE in patients with cancer and to compare current scoring systems for prediction of VTE before and after addition of these parameters. PATIENTS/METHODS: In a case-control study, in which patients with recently diagnosed cancer were followed-up for 6 months, we compared 20 patients who developed VTE (cases) and 140 patients with cancer without VTE (controls), matched for sex, age, and type and stage of cancer. We measured VWF, ADAMTS-13 (activity and antigen), P-selectin, D-dimer and F1 + 2 levels at baseline, and calculated both the Khorana score and the Khorana score expanded after addition of P-selectin and D-dimer levels. RESULTS: VWF levels were significantly higher in cases when compared with controls (326 ± 185% vs. 242 ± 158%) and correlated with advanced stage of cancer: localized, 185 [142; 222]; locally advanced, 240 [146; 257]; metastatic, 267 [153; 324] (mean [interquartile range]). The addition of two biomarkers, ADAMTS-13 activity and F1 + 2 levels, to the Khorana score improved receiver operating curves. CONCLUSIONS: von Willebrand factor and ADAMTS-13 are associated with the occurrence of VTE in patients with cancer. Moreover, addition of ADAMTS-13 and F1 + 2 levels to the Khorana score considerably increases the predictive value for VTE.

Nasal carriage of Staphylococcus aureus in dairy sheep.

The purpose of this study was to assess the prevalence of Staphylococcus aureus nasal carriage of dairy sheep in farms producing cheeses manufactured with raw ewe's milk. The study showed that 29% of ewes carried S. aureus in their nares. The genetic diversity of the 136 isolates recovered from the anterior nares of the ewes, from the ambient air of the milking parlour and from cheeses was investigated using pulsed-field gel electrophoresis (PFGE) of DNA SmaI digests. The genotyping results showed that 75 out of 106 isolates recovered from nasal carriage in dairy sheep belonged to a dominant pattern (previously named OV) and a genetically related pattern (named OV'). The same profile (OV or OV') was found in the ambient air and cheeses, suggesting a continuum between isolates within these different compartments.

Cellular composition of Corynebacterium pseudotuberculosis pyogranulomas in sheep.

The cellular composition of 46 pyogranulomas experimentally induced with Corynebacterium pseudotuberculosis in sheep was determined by immunohistochemistry. Lesions localized in inoculation sites or draining lymph nodes consisted of macrophage and lymphocyte layers distributed around a necrotic center and surrounded by a fibrous capsule. In immature lesions, T cells of the CD4+ subset predominated, whereas in mature lesions proportions of CD8+ T lymphocytes and cells expressing the gamma/delta chains for the T cell receptor increased. Numerous pyogranuloma cells expressed the interleukin-2 receptor. In addition to these general characteristics, a large individual variability in the proportions of macrophage and T cell subsets was observed for lesions of the same age, in particular for epithelioid macrophages. This heterogeneity suggests a different cellular pattern in relation to the persistence or the elimination of bacteria by the host.

Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs.

The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored 1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and 2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteria into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.