Chrysotile and chrysophosphate chemical modification of the chrysotile surface and its effect on biological behavior.

Chrysotile asbestos was reacted with phosphorus oxychloride (POC) gas to produce a chemically modified fiber referred to as chrysophosphate. The presence of phosphorus and chlorine on the fiber surface and in small fiber bundles was verified by means of energy dispersive x-ray spectrometry and laser mass spectrometry. The altered fiber exhibits different physical-chemical properties when compared with the unaltered precursor material. In addition to marked surface changes, fibrils of the reacted material appear to be cross-linked increasing the size of particulates, fiber bundles and increasing their mechanical stability. The reacted specimens exhibit fewer fibrils reducing their surface area. In vitro testing using the human erythrocyte model showed the membranolytic activity of the reacted fiber to be substantially reduced to the background level measured for mechanical membrane breakage during manipulation. Membranolytic activity of unreacted chrysotile displayed values reported previously in the literature. These data support the observation made in other studies that fiber surface modification by means of an industrial process may be a method for reducing the biological potential of mineral particles. The membrane model is considered a useful and preliminary examination. These materials will require further testing in more complex in vivo systems. Some in vivo assays were performed on chrysophosphate with results that appeared to differ from our membrane tests. These differences are described and the variation of batch chemistry, stability of the reacted surface, and the resulting surface chemistry, are discussed.

Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step.

Breast lumps in pregnant women.

Breast lumps detected during pregnancy are generally benign and reflect fibroadenoma, lactating adenoma, cysts, infarction of the breast or galactocele. Although rare, the possibility of breast cancer must also be considered to avoid any delays in diagnosis. After patient questioning and clinical examination, the first imaging modality to use is ultrasound. No further assessment is called for if lesions are categorized as BI-RADS 2 and no suspicious clinical signs are observed. Depending on the clinical setting, lesions classified BI-RADS 3 require monitoring and mammographic assessment (which can be helpful in diagnosing cancer and incurs no risk to the embryo or fetus). If the clinical signs are unclear and/or the lesion(s) are categorized as ≥ BI-RADS 4a, then mammography and often biopsy should be performed. Strict BI-RADS scoring (American College of Radiology) should be applied, bearing in mind that benign lesions can appear suspicious during pregnancy, and some cancers can exhibit what seem to be reassuring characteristics.

A single-institution study of 117 pregnancy-associated breast cancers (PABC): Presentation, imaging, clinicopathological data and outcome.

BACKGROUND: This retrospective single-institution study was designed to describe the main clinical, radiological and histological features, as well as the outcome of pregnancy-associated breast cancer (PABC), with a special emphasis on imaging and diagnostic difficulties. MATERIAL AND METHODS: We reviewed all breast cancers diagnosed during pregnancy or during the 12 months following delivery at our institution, between 1993 and 2009. Out of a total of 16,555 new cases of breast cancer observed during this period, 117 PABC (0.7%) were diagnosed. RESULTS: Mean age at diagnosis was 33.7 years. Most cancers (81.2%) were diagnosed after delivery. Intermediate or high family risk was frequent (27.5%). The most common mode of presentation was a palpable mass (89.7%). Mean time to diagnosis was 5.8 months. Sensitivity for mammography was 80.9% and for ultrasound 77%. Most prognostic factors were unfavourable: frequent lymph node involvement (51.8%), high-grade tumours, hormone receptor negativity (45.9%) and HER2 positivity (38.7%). Treatments generally included surgery (61.7% mastectomies), radiotherapy (96%) and chemotherapy (79.6%). Overall 5-year survival was 81.8%. CONCLUSION: PABC is an uncommon but aggressive form of breast cancer and must be considered in the presence of any breast abnormality during pregnancy or the months following delivery. Mammography and ultrasound should both be performed at the slightest clinical suspicion. Radiologists must be aware that masses may lack typical malignant ultrasound characteristics. Biopsies should be largely performed.

Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised. Exclusion criteria included previously documented PAH, interstitial lung disease, and SSc overlapping with other connective tissue disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc (90% female; 80% white), with a median age of 57 years and median disease duration of 5 years. A total of 82% of patients were classified as New York Heart Association functional class I and II; of these patients, 177 had an echocardiogram at enrolment and 191 at any time during the study. Of those who met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients with mild impairment. Although specific tools were recommended for screening PAH in patients with SSc, results indicate that significant diagnostic care gaps still exist in the general rheumatology community. Better understanding and adherence to guidelines could improve the care and, ideally, outcomes of these high-risk patients.

From the transcription of genes involved in ectodermal dysplasias to the understanding of associated dental anomalies.

Orodental anomalies are one aspect of rare diseases and are increasingly identified as diagnostic and predictive traits. To understand the rationale behind gene expression during tooth or other ectodermal derivative development and the disruption of odontogenesis or hair and salivary gland formation in human syndromes we analyzed the expression patterns of a set of genes (Irf6, Nfkbia, Ercc3, Evc2, Map2k1) involved in human ectodermal dysplasias in mouse by in situ hybridization. The expression patterns of Nfkbia, Ercc3 and Evc2 during odontogenesis had never been reported previously. All genes were indeed transcribed in different tissues/organs of ectodermal origin. However, for Nfkbia, Ercc3, Evc2, and Map2k1, signals were also present in the ectomesenchymal components of the tooth germs. These expression patterns were consistent in timing and localization with the known dental anomalies (tooth agenesis, microdontia, conical shape, enamel hypoplasia) encountered in syndromes resulting from mutations in those genes. They could also explain the similar orodental anomalies encountered in some of the corresponding mutant mouse models. Translational approaches in development and medicine are relevant to gain understanding of the molecular events underlying clinical manifestations.

Self-limited febrile syndromes temporally associated with the use of propofol for sedation in gastrointestinal endoscopic procedures.

PURPOSE: To investigate cases of febrile illnesses in patients who received propofol for sedation during gastrointestinal endoscopy. METHODS: Active case finding for patients who underwent endoscopy between 1 April and 30 May 2007 and suffered unexplained fever, chills, or myalgia within 48 hour after the procedure. We reviewed medications and clinical practices to find factors associated with the reactions. RESULTS: Seventy-four cases at eight facilities in five states were identified yielding a rate of 36 reactions per 1000 procedures, compared with a baseline rate of 0.6 per 1000. The majority of patients experienced self-limited fever (89.2%), chills (73.0%), or myalgia (63.5%). Blood samples from five patients were collected for culture; no organisms grew. All health care facilities that reported cases and fully participated in the investigation (n = 7) had received a common lot of propofol just before recognition of the first case. Bacterial endotoxin and sterility testing on unopened vials from this lot of propofol showed no abnormalities. Cases terminated after facilities stopped using the associated lot of propofol. CONCLUSIONS: We found a temporal association between a particular lot of propofol and an outbreak of febrile illnesses at several healthcare facilities performing endoscopy. When propofol is used to sedate patients for endoscopy, fever is a rare outcome and healthcare professionals should investigate clusters of these reactions. Post-procedure surveillance is important to identify possible medication reactions.

[Mammographic evaluation of dense breasts: techniques and limits]. / Exploration des seins denses en mammographie: techniques et limites.

Breast density is a radiological concept based on the proportion of radiopaque glandular tissue relative to radiolucent fatty tissue. Mammographic evaluation of dense breasts is more difficult, related to technical difficulties, with decreased rates for detection and characterization of breast lesions, resulting in reduced sensitivity with increased number of interval cancers at routine follow-up when compared to radiolucent breasts. We will review the definition of dense breasts and their frequency, especially their relationship with the age of patients. We will discuss the current technical problems and the impact of breast density on the efficacy of conventional mammography. We will discuss the value of digital mammography, the role of computer assisted diagnosis (CAD) systems and tomosynthesis in the evaluation of dense breasts.

Prevention and treatment of postoperative pain with particular reference to children.

Pain therapy is an important aspect of medical practice for patients of all ages, to optimize care, to obtain an adequate quality of life and to improve their general conditions. Pain is among the most prevalent symptoms experienced by patients undergoing surgery. The success of postoperative pain therapy depends on the ability of the clinician to assess the presenting problems, identify and evaluate pain syndromes and formulate a plan for comprehensive continuing care. The prevalence of acute pain has led to the need to develop techniques for the assessment and management of this symptom in order to focus the attention on an interdisciplinary therapeutic approach (including pharmacologic, cognitive-behavioral, psychologic and physical treatment) and on the timing of different interventions (pre and postoperative). In this chapter we describe the principal therapeutic approaches to control pain in post-operative patients, such as non-opioid, opioid and adjuvant analgesics with particular attention in paediatric age. Moreover we report the principal scales to assess the pain intensity in the post-operative period. The need of a multidisciplinatory team and of a pre and postoperative pain management program represents an important goal in order to obtain effective pain relief and optimize pediatric care and rapid recovery. The introduction of a perioperative team service will improve the approach to pain management programs and it is considered the most important challenge for future.

Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure.

BACKGROUND: Oxidative stress is increased in patients with congestive heart failure and can contribute to the progressive deterioration observed in these patients. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of endogenous antioxidants, such as vitamin E. OBJECTIVE: We aimed to determine whether vitamin E supplementation of patients with advanced heart failure would modify levels of oxidative stress, thereby preventing or delaying the deterioration associated with free radical injury. DESIGN: Fifty-six outpatients with advanced heart failure (New York Heart Association functional class III or IV) were enrolled in a double-blind randomized controlled trial for 12 wk. At a baseline visit and at 2 follow-up visits, blood and breath samples were collected for the measurement of indexes of heart function and disease state, including malondialdehyde, isoprostanes, and breath pentane and ethane. Quality of life was also assessed at baseline and after 12 wk of treatment. RESULTS: Vitamin E treatment significantly increased plasma concentrations of alpha-tocopherol in the treatment group but failed to significantly affect any other marker of oxidative stress or quality of life. In addition, concentrations of atrial natriuretic peptide (a humoral marker of ventricular dysfunction), neurohormonal-cytokine markers of prognosis, tumor necrosis factor, epinephrine, and norepinephrine were unchanged with treatment and were not significantly different from those in the control group. CONCLUSION: Supplementation with vitamin E did not result in any significant improvements in prognostic or functional indexes of heart failure or in the quality of life of patients with advanced heart failure.

Side effects, quality-of-life issues, and trade-offs: the patient perspective.

Increasingly effective adjuvant treatments of invasive breast cancer and their widespread use have improved survival rates. Given the timing required by its use, adjuvant therapy requires the patient to absorb complex medical data and make challenging trade-offs shortly after initial diagnosis. However, many women are unprepared or unable to optimize adjuvant treatment decisions while experiencing the shock and dismay that often follow the confirmation of an invasive breast cancer diagnosis. Each woman needs to know the facts and circumstances of her own case and to fully understand the benefits and risks of adjuvant therapy. Only then can she, with her medical team, choose those therapies that will maximize her benefit as a patient and as a survivor in all aspects of her life, over both the short and longer term. To help the patient accomplish these goals, individualized practical knowledge that complements population-based advances in survival is critically needed. Considerable focus, study, and cross-disciplinary collaboration will be required to compile successful, integrated approaches to adjuvant therapy that reflect varying patient contexts and concerns. Other crucial ingredients are the investment of resources in recently established research fields (such as the tracking of psychosocial outcomes and delayed morbidity) and informed guidance from patient advocates. To accelerate patient-centered progress in adjuvant therapy for breast cancer, areas that need attention include targeted public education programs; patient information and informatics; treatment selection and decision-making tools; and interventions and therapies to improve quality of life for patients, survivors, and their families. Underlying all of these efforts should be culturally competent, multigenerational approaches to communicating effectively with diverse patients and family members in multiple clinical and community settings.

Primary fallopian tube carcinoma with isolated torsion of involved tube.

BACKGROUND: Primary fallopian tube carcinoma (FTC) is an aggressive but rare tumor. Worldwide, more than 1,500 cases have been published, and about 20 new cases are added every year. Isolated fallopian tube torsion (IFTT) is an unusual and uncommon event. CASE: We report a 69-year-old Caucasian woman, Gravida 4, Para 3, with a long history of hypertension, diabetes mellitus with retinopathy and neuropathy, and history of extensive coronary artery disease, for which a triple-by-pass graft was performed. She was placed on anticoagulation therapy. Subsequently, she developed intermittent vaginal bleeding. RESULTS: We reviewed and discussed the symptoms and work-up of the patient in detail. She underwent exploratory laparotomy, and primary FTC with isolated torsion of the involved fallopian tube was diagnosed. Peritoneal washings, omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. CONCLUSION: Review of the English literature on the presenting symptoms and diagnostic management of primary FTC and IFTT is presented.

[Brainstem acoustic evoked potentials in children with developmental disabilities--a useful tool for differential diagnosis]. / Frühe akustisch evozierte Potentiale bei Kindern mit Entwicklungsstörungen--eine sinnvolle Ergänzung der Diagnostik?

In a retrospective study brainstem acoustic evoked potentials (BAEP) were evaluated in 222 children with psychomotor retardation or dysmorphic signs. Registrations were done, when no clear response to acoustic stimuli of medium intensity (60-80 dBA) could be obtained during clinical examination. Only 118 children (53%) had normal BAEP. 50 patients (22%) suffered from hearing impairment. 39 children (17%) showed disturbances of neuronal conduction. In 15 cases (7%) a combination of both conditions occurred. The mean age of our children with hearing impairment was 33.1 months, no case having been diagnosed before. In 57% the impairment was of the conductive type with an amount of less than 40 dB nHL This type was predominant in children with skeletal dysplasias (43%), chromosomal aberrations (43%) and malformation syndromes (40%). Severe hearing deficits of the sensorineural type with more than 69 dB nHL were found in children with malformation syndromes (28%), perinatal injuries (23%) and cns malformations (16%). As far as reference data were available, the hearing impairment in the BAEP was confirmed in 92% by our pedaudiologists. As a consequence hearing aids were first prescribed in 10 children, their medium age being 33.6 months. In 18 cases grommets were inserted. 9 children required paracentesis and 4 adenotomy. Disturbances of neuronal conduction with increased interpeak latencies and deformed potentials were predominantly found in the group of children with neurometabolic diseases (67%) and cns malformations (32%). Early diagnosis of hearing impairment in children with psychomotor retardation remains a problem as it is in the general population. More attention in clinical examination and appropriate screening is necessary. BAEP provide a powerful tool for hearing screening and additional information for differential diagnosis especially in children with neurometabolic diseases.

A risk assessment for exposure to glass wool.

Synthetic vitreous fibers (SVFs) have been widely used as insulation material in places where asbestos was used many years ago and therefore the hazards have been compared. Since the three principal types of asbestos fibers types have caused lung cancer at high exposures, there is a widely held belief that all fibers are carcinogenic if inhaled in large enough doses. Hence, on a morphological basis, SVFs have been studied for their carcinogenic potential. However, there is considerable evidence that differences exist among fibers in their potency to produce a carcinogenic response. In this attempt to carry out a numerical risk assessment for the installers of blown glass wool (fiber) insulation, we start with a characterization of the material; then we review the exposures both in manufacturing and installation. Neither the epidemiological studies of human exposure nor the animal studies have shown a marked hazardous effect from glass wool and we can therefore be sure that any effect that might exist is small. But in this case, as in many other situations where there is a potential hazard, society desires further reassurance and therefore we have made a mechanistic calculation. There are good estimates of the risk associated with exposure to chrysotile asbestos at high exposures and doses. We have therefore taken these numbers and discussed how much less risky an exposure to glass wool fibers might be. We conclude that for a given fiber count, glass wool is five to ten times less risky (and of course the risk might be zero). The risk for a nonsmoking installer of glass wool fiber insulation who wears a respirator is about 6 in a million (and might be zero) per year. This means that out of a million installers there might be six lung cancers from this cause every year or out of 10,000 installers there might be one in 16 years. The low risk of 6 in a million per year of a worker blowing glass wool is consistent with the fact that no one has found any of cancer attributable to the manufacture or installation of glass wool fibers in spite of diligent searches. This is compared with several other occupational risks. Nonetheless common prudence suggests that any installer of blown glass wool fiber insulation wear a respirator.

A risk assessment for exposure to grunerite asbestos (amosite) in an iron ore mine.

The potential for health risks to humans exposed to the asbestos minerals continues to be a public health concern. Although the production and use of the commercial amphibole asbestos minerals-grunerite (amosite) and riebeckite (crocidolite)-have been almost completely eliminated from world commerce, special opportunities for potentially significant exposures remain. Commercially viable deposits of grunerite asbestos are very rare, but it can occur as a gangue mineral in a limited part of a mine otherwise thought asbestos-free. This report describes such a situation, in which a very localized seam of grunerite asbestos was identified in an iron ore mine. The geological occurrence of the seam in the ore body is described, as well as the mineralogical character of the grunerite asbestos. The most relevant epidemiological studies of workers exposed to grunerite asbestos are used to gauge the hazards associated with the inhalation of this fibrous mineral. Both analytical transmission electron microscopy and phase-contrast optical microscopy were used to quantify the fibers present in the air during mining in the area with outcroppings of grunerite asbestos. Analytical transmission electron microscopy and continuous-scan x-ray diffraction were used to determine the type of asbestos fiber present. Knowing the level of the miner's exposures, we carried out a risk assessment by using a model developed for the Environmental Protection Agency.

Rapid and efficient cloning of proviral flanking fragments by kanamycin resistance gene complementation.

We have developed a technique for the rapid cloning of unknown flanking regions of transgenic DNA. We complemented a truncated kanamycin resistance gene of a bacterial plasmid with a neomycin resistance gene fragment from a gene transfer vector. Optimized transformation conditions allowed us to directly select for kanamycin-resistant bacteria. We cloned numerous proviral flanking fragments from growth factor-independent cell mutants that were obtained after infection with a replication incompetent retroviral vector and identified integrations into the cyclin D2 and several unknown genomic sequences. We anticipate that our method could be adapted to various vector systems that are used to tag and identify genes and to map genomes.

Asbestos in the lungs of persons exposed in the USA.

Tissues obtained at autopsy or biopsy from 81 workers and 2 household persons, were chemically digested. The asbestos fibres recovered were characterized by analytical transmission electron microscopy. Among the 83 causes of death were 33 mesotheliomas, 35 lung cancers, 12 asbestosis and 3 from other cancers. Of the three major commercial asbestos fibre types, amosite was found to be the most prevalent fibre, occurring in approximately 76% of the cases, followed by chrysotile in approximately 60% and crocidolite in approximately 24%. Amosite and chrysotile were observed as the single commercial fibre in approximately 22 and approximately 17% of the cases respectively, whereas crocidolite and tremolite were found as the single fibre type in only approximately 2.5% of the cases. Among the fifteen cases where chrysotile and tremolite occurred together, the amount of chrysotile fibre always exceeded tremolite. However, tremolite was also found in ten additional cases where chrysotile was not detected. Amosite was present in four, amosite plus crocidolite in three, and crocidolite alone in one. Amosite was present in all of the insulation workers' lungs studied and was found in the highest concentration in this exposure category. The highest chrysotile concentration was found among workers in general trades. Although most prevalent in shipyard workers lungs, crocidolite concentration is not statistically different among the exposure groups studied. Although crocidolite was found in twenty cases, amosite accompanied it in eighteen of these. Eleven of the 20 cases were from shipyard workers. Of the 8 mesothelioma cases, 7 also contained amosite. Crocidolite alone only occurred in 1 of the 33 mesothelioma cases analysed. We concluded the following: crocidolite exposure occurred among USA insulators and a large percentage of other workers as well; insulation workers are primarily exposed to amosite; mixed fibre exposures are associated with more mesotheliomas than single fibre exposures; chrysotile only exposure is associated with approximately 12% of the mesothelioma cases studied; and if tremolite exposure is associated with chrysotile exposure, the chrysotile amount exceeds that for the associated tremolite.