Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

BACKGROUND: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. METHODS: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. RESULTS: The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. CONCLUSIONS: MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Clinical toxicology and management of intoxications with synthetic cathinones ("bath salts").

Synthetic cathinones are synthetic derivatives of the natural cathinone, one of the psychoactive compounds present in Catha edulis (khat). There are at least 12 different types of synthetic cathinones, with mephedrone and 3,4-methylendioxypyrovalerone (MDPV) being the most commonly used by the purchasers. The legal control of these substances is especially difficult because when a specific compound is banned, a new slightly modified chemical variant is introduced into the market. It has been described that patients after taking synthetic cathinones may show signs and symptoms of the sympathicomimetic toxidrome, including agitation, psychosis, tachycardia, hypertension, and seizures. Furthermore, some cases of deaths related to their consumption have also been reported. Nowadays, there is no established treatment protocol for the clinical management of these intoxications. Because of this, we have developed some recommendations that may be useful to determine the treatment of these patients.

Neurotoxicidad asociada a oxaliplatino en la práctica clínica asistencial / Oxaliplatin-associated neurotoxicity in clinical practice

Objetivos: Determinar la presencia de neurotoxicidad asociada a oxaliplatino en la práctica clínica asistencial, la gravedad de la misma y el manejo clínico relacionado con este efecto adverso. Método Estudio observacional retrospectivo que incluyó pacientes diagnosticados de cáncer colorrectal y que iniciaron un esquema de quimioterapia basada en oxaliplatino durante el año 2008 en un hospital de segundo nivel. Los datos se obtuvieron del programa de prescripción de Onco-Hematología propio del hospital y de las historias clínicas informatizadas. Se recogieron variables relacionadas con las características clínicas de los pacientes, con el tratamiento antineoplásico, con la neurotoxicidad asociada a oxaliplatino, así como con su manejo clínico. Resultados Se incluyó un total de 64 pacientes. La presencia de neurotoxicidad se situó en un 65,6%, presentándose mayoritariamente de forma leve o moderada. Alrededor de una tercera parte de los pacientes que presentaron este efecto adverso requirió un cambio en la prescripción de oxaliplatino. Se determinó una relación estadísticamente significativa (p=0,0004) entre dosis acumuladas de oxaliplatino y presencia de toxicidad neurológica. Conclusiones La presencia de neurotoxicidad asociada a oxaliplatino y su distribución en función de su gravedad, es similar a la descrita en literatura médica. El número de pacientes que requiere un cambio en la prescripción de oxaliplatino podría justificar la necesidad de diseñar estudios que valoren las consecuencias clínicas asociadas a estas modificaciones. Consideramos que es necesario el desarrollo de estrategias neuroprotectoras efectivas que garanticen la seguridad y calidad de vida de estos pacientes (AU)

Objectives: To evaluate the presence and severity of oxaliplatin-associated neurotoxicity inclinical practice and the clinical management of this adverse side effect. Method: Observational retrospective study including patients diagnosed with colorectal cancer that started an oxaliplatin-based chemotherapy regimen during 2008 at a secondary hospital. Data were obtained from an onco-haematological prescription programme at the hospital and from digital clinical histories. We compiled variables related to the clinical characteristics of the patients, antineoplastic treatment, neurotoxicity associated with oxaliplatin, and clinical management of this issue. Results: Our study included a total of 64 patients. Neurotoxicity was recorded in 65.6% of cases, usually in mild or moderate forms. In approximately one third of patients who developed this adverse effect, the oxaliplatin prescription had to be modified. We observed a statistically significant relationship between cumulative oxaliplatin doses and the presence of neurological toxicity (P=.0004).Conclusions: The presence of oxaliplatin-associated neurotoxicity and its distribution based onits severity was similar to rates published in the literature. The number of patients requiring a change in the oxaliplatin prescription could justify the need for studies that assess the clinical consequences of these modifications. We believe that effective strategies for neurological protection need to be developed in order to guarantee the safety and quality of life in these patients (AU)

[Oxaliplatin-associated neurotoxicity in clinical practice]. / Neurotoxicidad asociada a oxaliplatino en la práctica clínica asistencial.

OBJECTIVES: To evaluate the presence and severity of oxaliplatin-associated neurotoxicity in clinical practice and the clinical management of this adverse side effect. METHOD: Observational retrospective study including patients diagnosed with colorectal cancer that started an oxaliplatin-based chemotherapy regimen during 2008 at a secondary hospital. Data were obtained from an onco-haematological prescription programme at the hospital and from digital clinical histories. We compiled variables related to the clinical characteristics of the patients, antineoplastic treatment, neurotoxicity associated with oxaliplatin, and clinical management of this issue. RESULTS: Our study included a total of 64 patients. Neurotoxicity was recorded in 65.6% of cases, usually in mild or moderate forms. In approximately one third of patients who developed this adverse effect, the oxaliplatin prescription had to be modified. We observed a statistically significant relationship between cumulative oxaliplatin doses and the presence of neurological toxicity (P=.0004). CONCLUSIONS: The presence of oxaliplatin-associated neurotoxicity and its distribution based on its severity was similar to rates published in the literature. The number of patients requiring a change in the oxaliplatin prescription could justify the need for studies that assess the clinical consequences of these modifications. We believe that effective strategies for neurological protection need to be developed in order to guarantee the safety and quality of life in these patients.

Impact of cigarette smoke exposure on host-bacterial pathogen interactions.

The human respiratory tract of individuals with normal lung function maintains a fine-tuned balance, being asymptomatically colonised by the normal microbiota in the upper airways and sterile in the lower tract. This equilibrium may be disrupted by the exposure to insults such as cigarette smoke. In the respiratory tract, the complex and noxious nature of inhaled cigarette smoke alters host-microorganism interaction dynamics at all anatomical levels, causing infections in many cases. Moreover, continuous exposure to cigarette smoke itself causes deleterious effects on the host that can trigger the development of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. COPD is an irreversible airflow obstruction associated with emphysema, fibrosis, mucus hypersecretion and persistent colonisation of the lower airways by opportunistic pathogens. COPD patients keep a stable (without exacerbation) but progressively worsening condition and suffer periodic exacerbations caused, in most cases, by infections. Although smoking and smoking-associated diseases are associated with a high risk of infection, most therapies aim to reduce inflammatory parameters, but do not necessarily take into account the presence of persistent colonisers. The effect of cigarette smoke on host-pathogen interaction dynamics in the respiratory tract, together with current and novel therapies, is discussed.

Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers.

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection. LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)-kappaB, p38 and the inhibitor IkappaBalpha were studied by immunoassays. Gene expression was assessed by RT-PCR. Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1beta and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeable Haemophilus influenzae (NTHi)-dependent secretion of IL-8 and the activation of NF-kappaB and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells. Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteria-dependent cellular activation without compromising the internalisation of pathogens by airway cells.

Allergic respiratory disease and fungal remediation in a building in a subtropical climate.

An outbreak of allergic respiratory disease occurred in a new building that was characterized from initial occupancy by the presence of extensive visible mold (especially Aspergillus versicolor) on interior surfaces. Epidemiological study of the occupants of both the affected building and a comparison neighboring structure indicated high rates of respiratory and other symptoms among persons working in the affected building. Subsequent clinical evaluations of some persons occupying the building for up to five years identified several cases of building-related allergic respiratory disease, including asthma and hypersensitivity pneumonitis. Based on these findings, the building was evacuated before remediation began. The mycological goal of the three-year building restoration project was to reduce concentration of non-phylloplane fungi such as A. versicolor to the lowest feasible level. All visibly colonized materials in the building were discarded and all fine dust on interior surfaces was removed by vacuuming and/or damp wiping. A medical surveillance program utilizing serial self-reported questionnaires and readily available clinical evaluations was designed to monitor the health of building occupants after re-entry. Symptom rates just prior to building reentry were substantially lower than those found before evacuation and have remained unchanged after re-occupancy was completed. No new or recrudescent cases of illness are known to have occurred after building re-entry.

Building-associated pulmonary disease from exposure to Stachybotrys chartarum and Aspergillus versicolor.

The authors present an outbreak of disease associated with exposure to Stachybotrys chartarum and Aspergillus species. A courthouse and two associated office buildings had generated discomfort among employees for two years since initial occupancy. Multiple interventions had been unsuccessful An initial evaluation of 14 individuals identified three with potential asthma and three with symptoms consistent with interstitial lung disease. A clinical screening protocol to identify individuals who should be removed from work identified three likely and seven possible cases of building-related asthma. Detailed environmental and engineering assessments of the building identified major problems in mechanical system design, building construction, and operational strategies leading to excess moisture and elevated relative humidities. Moisture-damaged interior surfaces in both buildings were contaminated with S. chartarum, A. versicolor, and Penicillium species. Aspergillus species, especially A. versicolor, at concentrations of 10(1) to 10(4)/m3 dominated the indoor air under normal operating conditions. Bulk samples also revealed large quantities of Stachybotrys. A questionnaire survey of the three case and two control buildings documented between three- and 15-fold increases in symptoms. A nested case-control study suggested emphysematous-like disease in individuals meeting questionnaire definitions for cases. Replication of analysis strategies used in similar previous investigations suggested an association between worsening symptoms and decreased diffusing capacity of the lung. Performance on neuropsychological measures was similar for both cases and controls, although workers with symptoms reported increased levels of current but not past psychiatric symptomatology. Chemical analyses demonstrated the presence of satratoxins G and H. Cytotoxic laboratory analyses demonstrated the presence of agents with biological effectiveness in bulk materials. No association was seen between IgE or IgG antibodies and the presence of disease. This outbreak represents a likely human response to inhaled fungal toxins in indoor environments. Moisture indoors represents a public health issue currently inadequately addressed by building, health, or housing codes.

Health and immunology study following exposure to toxigenic fungi (Stachybotrys chartarum) in a water-damaged office environment.

There is growing concern about adverse health effects of fungal bio-aerosols on occupants of water-damaged buildings. Accidental, occupational exposure in a nonagricultural setting has not been investigated using modern immunological laboratory tests. The objective of this study was to evaluate the health status of office workers after exposure to fungal bio-aerosols, especially Stachybotrys chartarum (atra) (S. chartarum) and its toxigenic metabolites (satratoxins), and to study laboratory parameters or biomarkers related to allergic or toxic human health effects. Exposure characterization and quantification were performed using microscopic, culture, and chemical techniques. The study population (n = 53) consisted of 39 female and 14 male employees (mean age 34.8 years) who had worked for a mean of 3.1 years at a problem office site; a control group comprised 21 persons (mean age 37.5 years) without contact with the problem office site. Health complaints were surveyed with a 187-item standardized questionnaire. A comprehensive test battery was used to study the red and white blood cell system, serum chemistry, immunology/antibodies, lymphocyte enumeration and function. Widespread fungal contamination of water-damaged, primarily cellulose material with S. chartarum was found. S. chartarum produced a macrocyclic trichothecene, satratoxin H, and spirocyclic lactones. Strong associations with exposure indicators and significant differences between employees (n = 53) and controls (n = 21) were found for lower respiratory system symptoms, dermatological symptoms, eye symptoms, constitutional symptoms, chronic fatigue symptoms and several enumeration and function laboratory tests, mainly of the white blood cell system. The proportion of mature T-lymphocyte cells (CD3%) was lower in employees than in controls, and regression analyses showed significantly lower CD3% among those reporting a history of upper respiratory infections. Specific S. chartarum antibody tests (IgE and IgG) showed small differences (NS). It is concluded that prolonged and intense exposure to toxigenic S. chartarum and other atypical fungi was associated with reported disorders of the respiratory and central nervous systems, reported disorders of the mucous membranes and a few parameters pertaining to the cellular and humoral immune system, suggesting a possible immune competency dysfunction.

Cross-sectional follow-up of a flu-like respiratory illness among fiberglass manufacturing employees: endotoxin exposure associated with two distinct sequelae.

Over a period of 10 years, employees in a manufacturing plant experienced sporadic flu-like episodes after work in a basement containing a recirculated washwater mist. We report a cross-sectional study to define the flu-like illness and bioaerosol exposures. High concentrations of gram-negative bacteria (GNB) (> 10(7) cfu/ml) and endotoxin (range 34-46 micrograms/ml) were found in the water. Mist contained > 10(3) cfu/m3 of GNB, and endotoxin up to 13,900 to 27,800 ng/m3. Few fungi and thermotolerant Bacillus species and no Actinomycetes, Legionella species, or amoeba were found in washwater. Airborne levels of fungi were of the same species and magnitudes as outdoor samples. Subjects volunteered (n = 28) because of a history of flu-like symptoms or were randomly selected (n = 102) from workers with and without current exposure to the basement. No acute cases were examined. Cases did not fulfill criteria for hypersensitivity pneumonitis (HP) and high levels of IgG antibodies to water-borne antigens were not observed. However, among 20 subjects indicating a history of severe flu-like episodes (severe basement flu, SBF), diffusion capacity (DLCO) was significantly lower (p = 0.015) than among other workers. The prevalence of SBF was independent of smoking. Cases occurred in clusters, and SBF was more common among workers with intermittent exposure to the basement (19 cases) than with daily exposure (1 case). These findings suggest that SBF and associated chronically depressed DLCO resulted from toxic injury following high-level endotoxin exposure. Asthma was prevalent in the study population, particularly among employees with daily, rather than intermittent, exposure to endotoxin-containing mist (odds ratio 6.7, p = 0.02). Thus, endotoxin exposure in this study was associated with two distinct sequelae depending on the temporal pattern of exposure.

Past maternal experience of asthma, childhood morbidity, and the psychosocial impact of the disorder.

Both previous experience of asthma, either in person or in a close family contact, by the mother of an asthmatic child and the child's current morbidity may influence the psychosocial impact of the disorder. A questionnaire concerning prior asthma experience, current psychosocial impact, and morbidity was returned by the mothers of 124 young asthmatic children. Family communication was significantly worse in the past maternal contact group. There were significant trends between morbidity and family communication, emotional distress, and manipulation. No beneficial effect of previous experience of asthma on measures of psychosocial disturbance experienced by the mothers of asthmatic children was detected. Increased psychosocial disturbance was associated with higher morbidity from asthma in the child.

Practical aspects of sampling for organic dusts and microorganisms.

Air sampling for organic dusts and microorganisms was carried out in silos when moldy silage was discarded through the discharge chute. Concentrations of respirable dust and airborne viable microorganisms exceeded 20 mg/m3 and 1 x 10(9)/m3, respectively, when dry silage was removed from silos. Much lower concentrations of dust and microorganisms were present when wet silage was discarded. Impinger and filter cassette samplers were equally effective in collecting the hardy spores present in silage dusts.

Role of ventilation in the causation of building-associated illnesses.

The objective of this article is to provide the reader with a basic knowledge of the operation of heating, ventilation, and air-conditioning (HVAC) systems and to explain why many systems do not perform correctly. The flow of air through a typical HVAC system is described, and the correlation between system components and their potential to affect indoor air quality is addressed.

An outbreak of recurrent acute and chronic hypersensitivity pneumonitis in office workers.

Three episodes of an acute, flu-like illness, one studied in detail, were associated with manipulations on the central air handling system of an office building in Tennessee in the summer and early fall of 1981. Symptoms were compatible with acute hypersensitivity pneumonitis, although the time of onset revealed a biphasic epidemic curve. Breathing air not supplied through the central air handling system protected against disease. Ill persons had significantly more precipitins to agents cultured from the building than did controls. Symptoms suggestive of chronic hypersensitivity pneumonitis were also found. Chronic disease was associated with the presence of humidifiers at home, asthma, and longer work in the building. Acute disease occurred less frequently in smokers and persons who had previously worked in the building before 1976. Persons with acute disease were more likely to have chronic disease. No single etiologic agent could be identified. Because of difficulties with demonstrating safety for reoccupancy, the building was vacated and remains empty at this time.