Validity of luminometry and bacteriological tests for diagnosing intramammary infection at dry-off in dairy cows.

The objective of this cross-sectional study was to estimate the validity of laboratory culture, Petrifilm and Tri-Plate on-farm culture systems, as well as luminometry to correctly identify IMI at dry-off in dairy cows, considering all tests to be imperfect. From September 2020 until December 2021, we collected composite milk samples from cows before dry-off and divided them into 4 aliquots for luminometry, Petrifilm (aerobic count), Tri-Plate, and laboratory culture tests. We assessed multiple thresholds of relative light units (RLU) for luminometry, and we used thresholds of ≥100 cfu/mL for the laboratory culture, ≥50 cfu/mL for Petrifilm, and ≥1 cfu for Tri-Plate tests. We fitted Bayesian latent class analysis models to estimate the sensitivity (Se) and specificity (Sp) for each test to identify IMI, with 95% credibility interval (BCI). Using different prevalence measures (0.30, 0.50, and 0.70), we calculated the predictive values (PV) and misclassification cost terms (MCT) at different false negative-to-false-positive ratios (FN:FP). A total of 333 cows were enrolled in the study from one commercial Holstein herd. The validity of the luminometry was poor for all thresholds, with an Se of 0.51 (95% BCI = 0.43-0.59) and Sp of 0.38 (95% BCI = 0.26-0.50) when using a threshold of ≥150 RLU. The laboratory culture had an Se of 0.93 (95% BCI = 0.85-0.98) and Sp of 0.69 (95% BCI = 0.49-0.89); the Petrifilm had an Se of 0.91 (95% BCI = 0.80-0.98) and Sp of 0.71 (95% BCI = 0.51-0.90); and the Tri-Plate had an Se of 0.65 (95% BCI = 0.53-0.82) and Sp of 0.85 (95% BCI = 0.66-0.97). Bacteriological tests had good PV, with comparable positive PV for all 3 tests, but lower negative PV for the Tri-Plate compared with the laboratory culture and the Petrifilm. For a prevalence of IMI of 0.30, all 3 tests had similar MCT, but for prevalence of 0.50 and 0.70, the Tri-Plate had higher MCT in scenarios where leaving a cow with IMI untreated is considered to have greater detrimental effects than treating a healthy cow (i.e., FN:FP of 3:1). Our results showed that the bacteriological tests have adequate validity to diagnose IMI at dry-off, but luminometry does not. We concluded that although luminometry is not useful to identify IMI at dry-off, the Petrifilm and Tri-Plate tests performed similarly to laboratory culture, depending on the prevalence and importance of the FP and FN results.

Detection of calmodulin-binding proteins and calmodulin-dependent phosphorylation linked to calmodulin-dependent chemotaxis to folic and cAMP in Dictyostelium.

Calmodulin (CaM) antagonists, trifluoperazine (TFP) or calmidazolium (R24571), dose-dependently inhibited cAMP and folic acid (FA) chemotaxis in Dictyostelium. Developing, starved, and refed cells were compared to determine if certain CaM-binding proteins (CaMBPs) and CaM-dependent phosphorylation events could be identified as potential downstream effectors. Recombinant CaM ([35S]VU-1-CaM) gel overlays coupled with cell fractionation revealed at least three dozen Ca(2+)-dependent and around 12 Ca(2+)-independent CaMBPs in Dictyostelium. The CaMBPs associated with early development were also found in experimentally starved cells (cAMP chemotaxis), but were different for the CaMBP population linked to growth-phase cells (FA chemotaxis). Probing Western blots with phosphoserine antibodies revealed several phosphoprotein bands that displayed increases when cAMP-responsive cells were treated with TFP. In FA-responsive cells, several but distinct phosphoproteins decreased when treated with TFP. These data show that unique CaMBPs are present in growing, FA-chemosensitive cells vs. starved cAMP-chemoresponsive cells that may be important for mediating CaM-dependent events during chemotaxis.

Endogenous autoinhibitors regulate changes in actin tyrosine phosphorylation during Dictyostelium spore germination.

Phosphorylation of proteins on tyrosine residues has been shown to govern many cellular processes, but little work has focused on the role of tyrosine phosphorylation during germination. Under optimal conditions, D. discoideum spores synchronously germinate each liberating a single amoeba. The total amount of phosphotyrosine containing proteins observed in spores was greatest during quiescence with a gradual decline during spore activation and emergence of nascent amoeba. During dormancy, tyrosine residues of actin were heavily phosphorylated, but they gradually underwent dephosphorylation upon spore activation and this process continued through emergence. Interestingly, an endogenous autoinhibitor(s), which blocks germination, induces tyrosine phosphorylation of actin. Conversely, the removal of the autoinhibitor(s) was followed by a decrease in phosphorylation. Thus, during germination of Dictyostelium spores, actin is dephosphorylated, with the level of phosphorylation regulated by the autoinhibitor(s) and/or the autoactivator. This change in actin phosphorylation appears to play a direct role since actin dephosphorylation and reorganization is a necessary prelude to germination.

[Drug-induced hypersensitivity syndrome in internal medicine: diagnostic and therapeutic traps. Eight observations]. / Syndrome d'hypersensibilité médicamenteuse en pratique interniste: pièges diagnostique et thérapeutique. Huit observations.

PURPOSE: Drug-induced hypersensitivity syndrome (DIHS) is an acute and severe drug reaction. Manifestations include severe skin lesions, fever, nodal enlargement, blood eosinophilia and multisystemic involvement. The severe systemic manifestations of DIHS are responsible for a 10% mortality rate. The pertinence of corticosteroid therapy is discussed. METHODS: The authors report eight retrospective cases of DIHS obtained from the PMSI (Programme de Médicalisatiopn des Systèmes d'Information) between November 1991 and November 1998. RESULTS: The series consisted of five male and three female patients (mean age: 52.6 years; range: 23-83 years). The interval between the introduction of the drug and the onset of the reaction varied from two to eight weeks. Due to severe systemic manifestations, three patients were given corticosteroid therapy. Healing of skin and systemic disorders resolved with a mean delay of 4.4 weeks (range: 1 to 56 weeks). CONCLUSION: DIHS can be a diagnostic trap, as there are no diagnostic criteria for DIHS. Only the association of multiple arguments such as the time to the occurrence of symptoms, clinical similarity to many infectious illnesses, hypereosinophilia, atypical lymphocytosis, etc. may help guide diagnosis. DIHS can also be a therapeutic trap, as prompt withdrawal of the offending drug is essential to minimize morbidity. Although still controversial in the literature, the pertinence of corticosteroid therapy may be discussed in case of severe systemic effects. Patch testing can be a valuable tool to determine the responsibility of a drug; however it proves to be useful only when positive.

[Cutaneous reactions or necrosis from interferon alpha: can interferon be reintroduced after healing? Six case reports]. / Réactions cutanées ou nécrose à l'interféron alpha: peut-on reprendre l'interféron? A propos de six cas.

PURPOSE: Alpha, beta or gamma interferon (INF) are cytokines produced by cells in response to antigenic stimulation. They are used to treat various hepatic, hematological, oncological and neurological diseases. Cutaneous reactions (rash, alopecia, labial herpes, erythema, or induration at the site of injection, and more rarely cutaneous necrosis) represent 5 to 12% of side-effects observed in patients receiving INF. The authors report six cases of local cutaneous reactions to alpha INF, five of which corresponded to cutaneous necrosis. This makes them question the relevance of INF reintroduction. METHODS: The study included 5 male and 1 female patients (mean age: 59.1 years; range: 42 to 74 years old). Three patients had chronic hepatitis C, while three others presented a blood disease. RESULTS: Cutaneous necrosis occurred after 1 to 10 months of treatment. The mean time to healing was 16.2 weeks. Reintroduction of the drug including injection in other sites did not lead to recurrence of necrosis in five out of the six cases. CONCLUSION: INF-induced cutaneous necrosis does not depend on the type of INF, the site of injection, the dose and may occur 2 months to 9 years after treatment implementation. The exact mechanisms involved in cutaneous necrosis remain unknown. Morbidity is due to a very long time to healing (4 to 6 months). Futhermore, healing sometimes requires prior surgery. Physicians should be aware of the potential occurrence of erythema in patients treated by INF, as it is the first sign of necrosis. The site of injection should then be modified. In case of necrosis, risk factors for thrombophilia, factors reducing microcirculation (DHE, beta-blockers, cigarette smoking) should be investigated. INF injections should be cautiously reintroduced in other sites with the help of a nurse in case of self-injections prior to the occurrence of necrosis. Regarding self-injections patients' training should be emphasized.

[Methi-resistant Staphylococcus aureus in dermatological practice: origin, risk factors and outcome]. / Staphylococcus aureus métirésistant en dermatologie.

BACKGROUND: Increased frequency of methiresistant Staphylococcus aureus (MRSA) in inpatients is a day to day problem. OBJECTIVE: To determine the origin of MRSA, the causes for contamination, and potential complications in a department of Dermatology. PATIENTS AND METHODS: A retrospective study of patients hospitalized in a dermatology department with cutaneous MRSA during 1997-1998. We considered age, type and duration of dermatitis, geographic origin of patients on admission, previous hospitalizations, time between arrival in the ward and positive MRSA, and complications requiring systemic antibiotics. RESULTS: Out of 4579 of our patients, 53 (0.011 p. 100) had positive MRSA. They were on average 70.86 years-old (26 to 97). The most common underlying dermatitis was leg ulcers (30) and foot sores (4). Dermatitis had lasted for more than 1 month in 48 patients. Most of the patients (40) had their MRSA on admission to our ward. Twenty six patients admitted from home had MRSA; only 9 had never been in an hospital. Six patients had diabetes mellitus. Thirty two patients healed with local treatment for their dermatitis. Thirteen patients have had some complications (erysipela 1, osteoarthritis 3, septicemia 2, febrile syndrome 9). DISCUSSION: Most patients with MRSA had leg ulcers or foot sores, confirming liability of chronic wounds to MRSA colonizing. Thirty one out of 40 patients with MRSA at arrival had been previously hospitalized. Hospitalization increases the risk of MRSA contamination. Treatment of MRSA is essentially that of the underlying dermatitis. However, it is still necessary to monitor the lesion for complications.

[Analysis of the literature about drug-induced aphthous ulcers]. / Aphtes induits par les médicaments: analyse de la littérature.

OBJECTIVES: Analysis of the literature on drug-induced aphthous ulcers and mucosal ulcerations and evidence-based grading. MATERIAL AND METHODS: Four literature sources were analyzed. Three groups of key words were used: 1) oral, buccal, genital, mucosal; 2) ulcer, ulceration, aphthous, aphthosis; 3) induced, drug, adverse-effects, with cross-overs. Four grading patterns were used: presence of aphthous term or synonym, typical clinical description of aphthous ulcer, presentation suggesting diagnosis of aphthous ulcer, criteria defining likelihood of drug causality. RESULTS: We examined 66 of the 220 publications responding to our selection criteria. Typical clinical description of aphthous ulcer and/or clinical presentation suggesting the diagnosis of aphthous ulcer were noted for 8 compounds with likely or palausible patterns of causality. For 21 compounds, we found only aphthous term or synonym without a clinical description or presentation. DISCUSSION: Our review of the literature individualized a group of 8 compounds where the diagnosis of aphthous ulcers was plausible and another group of 21 compounds where the diagnosis of aphthous ulcers requires confirmation. The clinical relevance and limitations of this analysis are discussed. CONCLUSION: Drug-induced aphthosis is probably a real phenomenon. Causality of the 8 compounds in the first group is simply more fully documented than for the 21 compounds in the second group. A low evidence level may not confirm these hypotheses. Some drugs may have been incorrectly ruled out due to lack of information.

[Penile lichen sclerosus: follow-up study]. / Lichen scléreux génital masculin: étude de suivi.

INTRODUCTION: The aim of this work was to study the long-term course of patients with penile lichen sclerosus and atrophicus. PATIENTS AND METHODS: We reviewed the files of 16 patients followed at our university center from 1982 to 1997 for pathologically proven penile lichen sclerosus and atrophicus. Age at disease onset, duration of the disease course, presence of a triggering factor, initial localization, signs and symptoms, treatment given and its efficacy were recorded. RESULTS: Mean age at diagnosis was 52 years. Inaugural prepuce localizations were observed in 6 cases, involving the distal part of the penis and the glan in 3 cases. Concomitant involvement of the glan and the balanopreputial groove were seen in 6 cases. The localization was limited to the glan in one case. Six patients underwent posthectomy and one had dorsal plasty of the prepuce. The 9 other patients were treated medically with topical corticosteroids and/or androgens. One patient had died prior to evaluation. Among the 9 patients given medical treatment, lichen sclerosus persisted in 7, one developed a squamous cell carcinoma of the penis and one was cured. Among the 6 cases of surgical treatment, 5 were cured and 1 had persistent lesions. Considering the initial localization, long-term course showed that 7 of the 8 patients with a prepuce localization (alone or in association with glan involvement) were cured while the 7 patients with a lesion of the balanopreputial groove (alone or in association with glan involvement) or a lesion of the glan alone still had lichen sclerosus and atrophicus. The non parametric Fischer test showed that the chances of cure were better for preputial localizations than for balanopreputial localizations (p = 0.001) and that surgical treatment was more effective than medical treatment. DISCUSSION: This study of a small number of patients highlighted two points: prepuce localizations of lichen sclerosus and atrophicus cure better than balanopreputial localizations, and that medical treatment is partially effective in balanopreputial localizations. One patient developed squamous cell carcinoma of the penis. As the level of the cancer risk remains unknown, it would be important to provide the most effective treatment in all cases of penis lichen sclerosus and atrophicus.

[Drug hypersensitive syndrome caused by fluindione]. / Syndrome d'hypersensibilité médicamenteuse à la fluindione.

BACKGROUND: Fluindione (Previscan) is an oral anticoagulant prescribed in relay to heparin therapy for deep venous thrombosis, pulmonary embolism... The main complications with oral anticoagulants are bleeding. However, severe immuno-allergic complications, especially acute hepatitis, acute renal failure and acute bone marrow failure, have been described with phenindione therapy. OBSERVATIONS: The authors report herein the first five cases of drug-induced hypersensitivity syndrome due to fluindione. Clinical signs included erythroderma and severe systemic manifestations which occurred within 3 to 8 weeks after introducing the molecule. Sex ratio was four males for one female; their ages ranged from 53 to 84 years. Clinical signs included erythroderma (with photosensitivity in two patients), lymphadenopathy and fever evoking severe sepsis. In our observations, marked eosinophilia (5 cases), lymphocytosis, atypical lymphocytes (4 cases), hepatic cytolysis (4 cases), associated in 2 cases with hepatic cholestasis, and pulmonary signs were noted. Cutaneous eruption healed in about 3 to 6 weeks after withdrawal of the drug. In two cases, systemic steroids were required for the severity of systemic manifestations. Long after the acute episode and when steroids were stopped, patch testing with fluindione was still positive. DISCUSSION: To date, acute and/or severe skin diseases due to fluindione, associated or not with multisystemic involvement, have never been reported. This molecule is the most commonly used for the treatment of thromboembolic diseases. Patch testing is easy to perform and can help physicians find the responsible molecule. Moreover, skin manifestations are present only in 87 p. 100 of drug-induced hypersensitivity syndromes. Acute hepatitis and acute renal failure might be drug-induced hypersensitivity syndromes without cutaneous manifestations.

[Multicentric histiocytosis with hematological involvement]. / Histiocytose multicentrique avec atteinte hématologique.

INTRODUCTION: The aim of this work was to present a case of multicentric histiocytosis with haematologic involvement. CASE REPORT: A 68-year-old man presented with poor general health and a nodular eruption of the skin and larynx. On clinical examination there was an enlarged spleen and laboratory results revealed an inflammatory syndrome, platelet count 60,000 and myelemia with 10 p. 100 immature elements in a white cell count of 14,000. Pathology and ultrastructure examinations led to the diagnosis of multicentric histiocytosis. Bone marrow aspiration was normal. Pancytopenia then developed with bone marrow hypoplasia without infiltration. Corticosteroids then cyclophosphamide were uneffective for either the skin disease or the hematologic disorder. The patient developed severe buccal aphthosis which responded well to thalidomide. This treatment reduced the size and the number of skin nodules. Finally, renal failure of unknown origin was observed. DISCUSSION: Electron microscopy is essential for positive and differential diagnosis of atypical multicentric histiocytosis. Hematological disorders associated with multicentric histiocytosis may either be specific or totally independent.

[Pretibial epidermolysis bullosa and hypothyroidism]. / Epidermolyse prétibiale de l'hypothyroïdie.

BACKGROUND: We report a case of primary non-autoimmune hypothyroidism causing pretibial epidermolysis bullosa. CASE REPORT: A 70-year-old man with primary non-autoimmune hypothyroidism developed blisters of different ages on the lateral aspect of both legs. Pathology reported blisters with subepidermal cleavage. Direct immunofluorescence was negative. Electron microscope examination showed a variable cleavage level and diffuse infiltration of a granulous and amorphous microfibrillar substance. After hormone replacement therapy, euthyroidism was associated with a reduction in the number of bullae and finally complete remission. After 12 months follow-up, the patient has not experienced recurrence. DISCUSSION: Recurrence-free clinical improvement after hormone replacement therapy suggests the diagnosis of hypothyroidism pretibial epidermolysis bullosae. Mochizuki et al. described a similar case which rapidly regressed after hormone therapy but where the electron microscope showed a different cleavage level. These bullae appear to result from a mechanical mechanism due to their localization in areas exposed to friction and also to the presence of bullae of different ages. This hypothesis is confirmed by the presence of a variable level of cleavage and a substance dense to electrons at electron microscopy as well as by the skin weakness. Our case confirms the reality of hypothyroidism pretibial epidermolysis bullosa. Thyroid hormones should be assayed in patients presenting pretibial bullae.

[Methicilline-sensitive and methicilline-resistant Staphylococcus aureus related morbidity in chronic wounds: a prospective study]. / Etude prospective comparative de la morbidité des Staphylococcus aureus métisensibles et métirésistants dans les plaies chroniques.

OBJECTIVE: Staphylococcus aureus is the most common bacteria responsible for cutaneous infections. Its capacity to adapt has led to the selection of methicilline-resistant strains (MRSA). These strains create specific problems in their management in dermatology (mode of contamination, treatment, added costs, increased nosocomial risks). The objective of our study was to search for morbidity of MRSA in chronic cutaneous wounds in hospital settings and assess the need of systemic antibiotic therapy. PATIENTS AND METHODS: We have conducted a one-year prospective study. All the patients hospitalized in the department with leg ulcers or foot wounds were included. Following local sampling for bacteriological examination, three groups were constituted: methicilline-sensitive patients with staphylococcus aureus (MSSA), methicilline-resistant staphylococcus aureus patients and patients in whom these bacteria were absent. Only the first two groups were compared after studying the past history, clinical description of the wound at the start of the study, results of the infectious bacteriology and of the clinical and bacteriological evolution of the wounds. RESULTS: The two groups studied were similar in number, past history, clinical aspect and therapeutic management. Only malnutrition was more frequent in patients exhibiting MRSA. There was no difference with the evolution of the wounds. CONCLUSION: Our study did not reveal any difference in the morbidity of staphylococcus aureus in the cutaneous wounds whether methicilline sensitive or resistant. Systematic antibiotherapy is not justified in the absence of signs of infection.

Genetic and epigenetic changes in mammary epithelial cells identify a subpopulation of cells involved in early carcinogenesis.

Morphologically normal foci of epithelial cells exhibiting p16 inactivation have been found in several tissues and may be precursors to cancer. Our previous work demonstrates that cells lacking p16(INK4A) activity exhibit phenotypes associated with malignancy (Romanov et al. 2001). The acquisition of genomic instability occurs through the activation of telomeric and centrosomal dysfunction. Additionally, the activation of stress pathways such as COX-2 provides these cells with the mutagenic potential to survive adverse environments as well as the ability to migrate, evade apoptosis and immune surveillance, and summon sustaining vasculature. Examination of archived tissue from women with DCIS (ductal carcinoma in situ) reveals epithelial cells that overexpress markers of premalignant stress activation pathways and mirror the distinctive expression patterns of these markers observed in vitro. These epithelial cells are found within the premalignant lesion as well as in the field of morphologically normal tissue that surrounds the lesion. Here, we show that p16(INK4A)-silenced vHMEC cells exhibit a gene expression profile which is distinct, reproducible, and extends beyond the changes mediated by p16(INK4A) inactivation. The present work suggests that cells lacking p16(INK4A) activity exhibit critical activities which allow cells to evade differentiation processes that would be expected to terminate proliferation. All of these properties are critical to malignancy. These events may be useful biomarkers to detect the earliest events in breast cancer.

Photosensitivity with sulfasalazopyridine hypersensitivity syndrome.

Five weeks after the start of treatment with an association of sulfasalazopyridine and piroxicam, a 30-year-old woman presented with an eczematous eruption in light-exposed areas, hepatomegaly and fever (38 degrees C). Laboratory studies showed leukocytosis, eosinophilia and hepatic cytolysis. Treatment consisted of withdrawing the two drugs and topical steroids. The clinical signs regressed in 6 days. An increase in eosinophilia and hepatic cytolysis was observed until the tenth day, after which the trend reversed. Laboratory parameters were normal on the twentieth day. One month later, photopatch testing was performed. A patch test with sulfanilamide irradiated with UVA was positive. Clinical and laboratory findings were highly suggestive of drug hypersensitivity syndrome. The positive result from the UVA photopatch test with sulfanilamide suggests that sulfasalazopyridine was involved in the occurrence of hypersensitivity syndrome in our patient. We conclude that photodistributed eruptions can be observed in drug hypersensitivity syndrome with photosensitizing drugs.

Dermatofibrosarcoma protuberans in childhood.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor with a possibly misleading presentation. It is rare in childhood. We report an 18-month-old child with an acquired atrophic plaque of the left ankle. Based on clinical findings, initial proposed diagnoses included localized scleroderma and localized lipoatrophy. At the age of 5 years the plaque had increased in size and become a purplish color. Several firm nodules were seen at its periphery. A diagnosis of DFSP was proposed and confirmed histologically. A large surgical resection was performed. This case illustrates that DFSP may occur in childhood, during which initial diagnosis is generally more difficult than in adulthood.

Role of drug exposure in aphthous ulcers: a case-control study.

BACKGROUND: Drug-induced aphthous ulcers have been the subject of several isolated and heterogeneous case reports for the last three decades. OBJECTIVES: To perform a case-control study to evaluate the risks linked to drug exposure in aphthous ulcers. METHODS: Eighty patients with typical clinical patterns of aphthous ulcers and 152 control patients who had had consultations for skin tumours were studied. A standardized questionnaire, concerning clinical features, life-style and medications taken during the last month, was completed for each patient. RESULTS: Case patients had a much higher intake of medications than control patients, respectively, 5.1 and 2. 8 medications per patient (P < 0.0001). Multivariate paired analysis showed an association between aphthous ulcers and two classes of drugs: non-steroidal anti-inflammatory drugs (P < 0.001) and beta-blockers (P = 0.002). Smoking could have a protective effect against aphthous ulcers (P < 0.001). CONCLUSIONS: Previous case reports and the results of this study suggest a real link between beta-blockers and aphthous ulcers. Our study did not confirm a role of other drugs but a few interesting case reports with positive reintroduction have to be considered. These results could be beneficial for patients, as healing may occur when the incriminated drug is discontinued.