THOR-05F biofidelity evaluation in reclined and upright seated postures subjected to frontal crash pulses.

The THOR 5th percentile female dummy (THOR-05F) was evaluated for two seating postures/positions in frontal impacts using a generic automotive seat environment. The conditions included 2 crash pulses: a 15 km/h test that utilized 4.5 g acceleration and a 3-point restraint with 2 kN load limiter, and a 32 km/h test that utilized 9.5 g acceleration and a 3-point restraint with a 4.5 kN load limiter and pretensioner, and two seatback angles: 25°, a nominal upright posture, and 45°, a moderate reclined posture. The BRS scores were calculated using the NHTSA BioRank method. Overall biofidelity rating was consider excellent for both seating postures. This evaluation provides an understanding of the THOR-05F response and biofidelity evaluation of the ATD in two seating postures (nominal and reclined). This is essential in the assessment and development of safety measures in emerging ADS-equipped vehicles.

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

BACKGROUND: Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick's bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence. PATIENTS AND METHODS: A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates. RESULTS: Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P = 0.016). Sex (P = 0.53), premedication (P = 0.91), primary cancer location (P = 0.46) and chemotherapy regimen type (P = 0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P = 0.0015). CONCLUSION: This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs.

[Patients' satisfaction and waiting time in oncology day care centers in Champagne-Ardenne]. / Programme d'évaluation de l'administration des chimiothérapies en hôpital de jour en Champagne-Ardenne (PEACH) : satisfaction et délais d'attente des patients.

AIM: Quality of life of patients suffering from cancer may be influenced by the way healthcare is organized and by patient experiences. Nowadays, chemotherapy is often provided in day care centers. This study aimed to assess patient waiting time and satisfaction in oncology day care centers in Champagne-Ardenne, France. METHODS: This cross-sectional survey involved all patients receiving ambulatory chemotherapy during a one-week period in day care centers of Champagne-Ardenne public and private healthcare institutions participating in the study. Sociodemographic, medical and outpatient data were collected. Patient satisfaction was measured using the Out-Patsat35 questionnaire. RESULTS: Eleven (out of 16) oncology day care centers and 441 patients participated in the study. Most of the patients were women (n=252, 57.1%) and the mean age was 61±12 years. The mean satisfaction score was 82±14 (out of 100) and the mean waiting time between the assigned appointment time and administration of chemotherapy was 97±60 min. CONCLUSION: This study has shown that waiting times are important. However, patients are satisfied with the healthcare organization, especially regarding nursing support. Early preparation of chemotherapy could improve these parameters.

Kinematics of the unrestrained vehicle occupants in side-impact crashes.

A test series involving direct right-side impact of a moving wall on unsupported, unrestrained cadavers with no arms was undertaken to better understand human kinematics and injury mechanisms during side impact at realistic speeds. The tests conducted provided a unique opportunity for a detailed analysis of the kinematics resulting from side impact. Specifically, this study evaluated the 3-dimensional (3D) kinematics of 3 unrestrained male cadavers subjected to lateral impact by a multi-element load wall carried by a pneumatically propelled rail-mounted sled reproducing a conceptual side crash impact. Three translations and 3 rotations characterize the movement of a solid body in the space, the 6 degrees of freedom (6DoF) kinematics of 15 bone segments were obtained from the 3D marker motions and computed tomography (CT)-defined relationships between the maker array mounts and the bones. The moving wall initially made contact with the lateral aspect of the pelvis, which initiated lateral motion of the spinal segments beginning with the pelvis and moving sequentially up through the lumbar spine to the thorax. Analyzing the 6DoF motions kinematics of the ribs and sternum followed right shoulder contact with the wall. Overall thoracic motion was assessed by combining the thoracic bone segments as a single rigid body. The kinematic data presented in this research provides quantified subject responses and boundary condition interactions that are currently unavailable for lateral impact.

[Oral ulcerations]. / Les ulcérations de la bouche.

Oral ulcerations are frequent lesions resulting from numerous different causes. A precise anamnesis is mandatory to direct towards the diagnosis. It includes the type of the earliest lesion (blister/vesicle or ulceration), the number of lesions (isolated or numerous), the complaints (painful or asymptomatic), the disease evolution (acute, chronic, recurrent), the duration of the ulceration (a few hours, days, weeks, months, years...), the presence of adenopathies and/or the association with clinical lesions on other mucous membranes, on skin, on nails or on scalp. A traumatism or a drug reaction are the first aetiologies to be excluded. Chronic enteropathies or lupus erythematosus or other systemic diseases, especially those leading to immunosuppression, can be responsible for oral ulcerations. These diseases must be diagnosed and treated to obtain an improvement of the oral lesions. Laboratory studies such as microbiological isolation, serology or biopsy, are performed in accordance with the suspected diagnosis resulting from anamnesis and physical examination. Aphthous stomatitis and oral herpes infection present similar features such as symptomatology, recurrences, trigger factors, etc. Differential diagnosis is mandatory to treat correctly the disease. It is easier if the primary lesion (vesicle or ulceration) is observed or if herpes simplex virus is yielded. Oral blisters are uncommon; they especially concern erythema multiforme and bullous auto-immune diseases. A single ulceration directs towards a diagnosis of cancer or chancre. Lichen planus is a frequent disease of the oral mucous membrane with numerous clinical features: erosive and ulcerated lesions are often observed. In all cases, a symptomatic treatment is necessary against pain to permit nutrition, hydratation and good speech. An etiologic treatment is associated as soon as possible.

Comparison of Hybrid III child test dummies to pediatric PMHS in blunt thoracic impact response.

The limited availability of pediatric biomechanical impact response data presents a significant challenge to the development of child dummies. In the absence of these data, the development of the current generation of child dummies has been driven by scaling of the biomechanical response requirements of the existing adult test dummies. Recently published pediatric blunt thoracic impact response data provide a unique opportunity to evaluate the efficacy of these scaling methodologies. However, the published data include several processing anomalies and nonphysical features. These features are corrected by minimizing instrumentation and processing error to improve the fidelity of the individual force-deflection responses. Using these data, biomechanical impact response corridors are calculated for a 3-year-old child and a 6-year-old child. These calculated corridors differ from both the originally published postmortem human subject (PMHS) corridors and the impact response requirements of the current child dummies. Furthermore, the response of the Hybrid III 3-year-old test dummy in the same impact condition shows a similar deflection but a significantly higher force than the 3-year-old corridor. The response of the Hybrid III 6-year-old dummy, on the other hand, correlates well with the calculated 6-year-old corridor. The newly developed 3-year-old and 6-year-old blunt thoracic impact response corridors can be used to define data-driven impact response requirements as an alternative to scaling-driven requirements.

[Allergies to dental metals. Titanium: a new allergen]. / Les allergies aux métaux dentaires. Un allergène émergent: le titane.

Oral allergies are underdiagnosed by dental health professionals. Patients with an oral allergy complain of various symptoms such as burning or tingling sensations, with or without oral dryness or loss of taste, or of more general symptoms such as headache, dyspepsia, asthenia, arthralgia, myalgia. The signs of oral allergy include erythema, labial oedema or purpuric patches on the palate, oral ulcers, gingivitis, geographical tongue, angular cheilitis, perioral eczematous eruption, or lichenoid reactions localized on the oral mucosa. There is an increase in the prevalence of oral allergies to metals used in dental materials. Allergy to gold included in dental prosthesis has been well documented since the years eighties. Recently, titanium, used in orthopedic devices and oral implants, considered as an inert material, can induce toxicity or allergic type I or IV reactions. These reactions to titanium could be responsible for unexplained successive failure cases of dental implants in some patients (named "cluster patients"). The risk of an allergy to titanium is increased in patients who are allergic to other metals. In these patients, an evaluation of allergy is recommended, in order to exclude any problem with titanium medical devices. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

Oral allergies to dental materials.

Oral allergies represent a pathological entity not well known nor diagnosed by dental health professionals. The purpose of this work is to present an information relative to the multidisciplinary steps to be done to solve allergy problems. Three clinical examples of contact oral allergies (to mercury, or gold, or methacrylates) are presented, as to illustrate signs and symptoms of an oral allergy to the more frequent dental materials implied.We discuss the problem of oral allergies from what is known from the scientific literature. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

[How to diagnose and how to treat diseases of the genital mucosa?]. / Reconnaître et traiter les lesions des muqueuses génitales féminines.

The genital area in women is covered by a keratinized squamous stratified epithelium outside the body (vulva), and a non keratinized epithelium inside the body (vagina). These characteristics can have an effect on the clinical aspects of the diseases and/or on the choice of the treatment. Symptoms (itching, pain, vaginal discharge), preferential localisation of skin diseases (psoriasis, lichen planus, lichen sclerosus, atopic dermatitis and allergic contact dermatitis, irritative dermatitis) and the aspect of primary lesions are to be investigated. The implication of this region in sexual activity places it at risk of sexually transmitted diseases (STD's) and dyspareunia. These have numerous causes that have to be sought and taken care of, often by multidisciplinary teams. After a careful history and clinical examination, additional tests allow to exclude infections or confirm a skin condition or neoplasia by a skin biopsy. If contact dermatitis is suspected, specific allergy testing is done. Treatment starts with correction of harmful habits (excessive use of soaps, inappropriate cosmetic products,...) that add to the local irritation. Patients are then reassured of common misconception regarding cancer, STD's and fertility. In the vast majority of cases, the treatment will target an infection (fungal, bacterial, STD's), will relieve irritation by the use of local immunosuppressant drugs (local corticosteroids) and/or relief itching symptoms with anti-histamine drugs.

[Economic evaluation of at home subcutaneous and intravenous immunoglobulin substitution]. / Etude comparative du coût du traitement à domicile des immunoglobulines intraveineuses ou sous-cutanées à visée substitutive.

BACKGROUND: Intravenous (IV) and subcutaneous (SC) immunoglobulin (Ig) administration is a safe and an efficacious treatment in patients with IgG deficiency. Home administration of IV Ig and SC Ig has recently been approved in France. Most of the patients treated in hospital ask for home treatment. Some patients prefer monthly IV administration, others weekly SC administration. MATERIAL AND METHODS: We evaluated in details the cost of both of these practices. We currently use electric pumps for both IV and SC administration which are fixed to the patient giving complete freedom and mobility. RESULTS: For 20 g administrated per 4 week, the total cost of home treatment is 1,518 euro with SC Ig and 1,033 euro with IV Ig. For 40 g administrated per 4 week, the total cost of home treatment is 2,507 euro to 2,729 euro with SC Ig and 2,034 euro with IV Ig. The difference is mainly explained by the cost of renting the electric pumps and by the cost of furniture for SC administration. The choice of home Ig substitution must be given to all patient receiving treatment in hospital. CONCLUSIONS: Home IV and home SC perfusions are two possible options each different with there own advantages and disadvantages. The cost of each procedure must be known by the medical staff.

[Genital herpes]. / L'herpès génital.

In developed countries, genital herpes is, together with papillomavirus infections, among the most common sexually transmitted diseases. HSV is a dormant virus causing lifelong infection and recurring with or without clinical symptoms. Exposure to lesions and to asymptomatic viral shedding result in transmission. Thus, in most cases, finding the exact path of viral transmission is impossible. The diagnosis is often clinical: classic lesion presentation and typical localised recurrences. The confirmation of the diagnosis is obtained by virus isolation, the most sensitive method is PCR but viral culture techniques are the most widely used. Today, the nucleoside analog antivirals (aciclovir, valacicovir, famciclovir, penciclovir), are the only efficient and well tolerated treatments for genital herpes. The virus resistance to these molecules in immunocompetent patients is very low and has not increased since their introduction. Thus, for these patients, treatment failure is generally due to low bioavailability which is resolved by increasing doses. Ideally a vaccine against herpes should be prophylactic (preventing primary infection) and therapeutic (preventing recurrences). None is available today despite intensive research for the past two decades.

[Polymyositis induced or associated with lipid-lowering drugs: five cases]. / Polymyosites induites ou associées aux traitements hypolipémiants? A propos de cinq cas.

PURPOSE: Rhabdomyolysis and myositis are rare, dose-related complications of statins and fenofibrates. The outcome is favorable as a rule with rapid regression after stopping the responsible drug. Recently, various auto-immune disease with evidence of hypersensitivity to HMG-CoA reductase inhibitors or fibrates drugs have been reported. Less than ten cases of dermatomyositis and polymyositis due to cholesterol-lowering drugs (CLD) have been previously reported. Five more cases polymyositis associated with CLD are reported. METHODS: Symptoms were compatible with diagnosis of polymyositis according to Bohan and Peter and with previous reported criteria for drug-induced myopathy in all cases. None of these patients had previous other connective tissue disorders. RESULTS: Five patients (median age 68 [54-78], female N =4) with CLD treatment (statin N =4, fenofibrates N =1) have developed iatrogenic polymyositis. All of them presented both proximal muscular weakness and increased muscle enzyme levels. One patient had iatrogenic antisynthetase syndrome characterized by mechanic's hand, Raynaud's phenomenon and anti JO1 antibodies. One other had sclerodermic hand oedema. Antinuclear antibodies were positive in 4 cases and muscle biopsy revealed polymyositis infiltrate in 4 cases. CLD treatment was discontinued with partial clinical improvement in 3 cases. Clinical remission was obtained with corticosteroid (N =5) in association with immunosuppresive agents in 3 cases. CONCLUSION: Muscular symptoms in patient with CLD treatment could be the first symptom of a polymyositis revealed or increased by this treatment and must encourage physician with antinuclear antibodies screening especially in case of proximal muscular weakness and increased muscle enzyme levels.

[The dermatology department]. / Le Service de Dermatologie.

The department of dermatology has developed a broad clinical activity with a particular expertise in oncology, allergology, psoriasis and gynecological dermatology. Research has also been developed in these areas.

Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection.

Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found. Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue. These procedures are often painful and are characterized by a high relapse rate. We report here what is to our knowledge the first double-blind, placebo-controlled study of the use of cidofovir, a nucleotide analogue, for the treatment of genital papillomavirus infections. Thirty patients were enrolled in the study; 19 received cidofovir, and 11 received placebo. The median number of warts and the median baseline wart area were comparable for both groups. Nine (47%) of 19 patients in the cidofovir group had a complete response (total healing), compared with 0 of the patients in the placebo group (P=.006). None of the patients in the cidofovir group experienced progression of the disease, compared with 5 (45%) of 11 patients in the placebo group. The side effects recorded for both groups were comparable.

Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors.

The lymphatic vessels (lymphatics) play an important role in channeling fluid and leukocytes from the tissues to the secondary lymphoid organs. In addition to driving leukocyte egress from blood, chemokines have been suggested to contribute to leukocyte recirculation via the lymphatics. Previously, we have demonstrated that binding sites for several pro-inflammatory beta-chemokines are found on the endothelial cells (ECs) of lymphatics in human dermis. Here, using the MIP-1alpha isoform MIP-1alphaP, we have extended these studies to further support the contention that the in situ chemokine binding to afferent lymphatics exhibits specificity akin to that observed in vitro with the promiscuous beta-chemokine receptor D6. We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6 probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive lymphatics were also abundant in mucosa and submucosa of small and large intestine and appendix, but not observed in several other organs tested. In lymph nodes, D6 immunoreactivity was present on the afferent lymphatics and also in subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6-positive. Peripheral blood cells and the ECs of blood vessels and high endothelial venules were consistently nonreactive with anti-D6 antibodies. Additionally, we have demonstrated that D6 immunoreactivity is detectable in some malignant vascular tumors suggesting they may be derived from, or phenotypically similar to, lymphatic ECs. This is the first demonstration of chemokine receptor expression by lymphatic ECs, and suggests that D6 may influence the chemokine-driven recirculation of leukocytes through the lymphatics and modify the putative chemokine effects on the development and growth of vascular tumors.