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        Myxoid Tumours of Soft Tissue


July 2007

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Soft Tissue Pathology

Case Index

Infectious Disease Online; INDEX: A-D ; INDEX: E-L ; INDEX: M-P INDEX: Q-Z ; FUNGAL DISEASE ; VIRAL DISEASE.

Anatomy and Histology of the Normal Lung and Airways

Examination of pulmonary and pleural biopsies

Useful chromatic and immunostains in pulmonary pathology

Percutaneous Needle and Trucut Biopsy Specimen

Bronchial Biopsy Specimen

Transbronchial Biopsy Specimen

Transbronchial biopsy in lung transplant recipients

Open lung biopsy

Lobectomy and pneumonectomy specimen

Histopathological reporting of pulmonary parenchymal biopsies

Histopathological reporting of pulmonary biopsies in cases of Idiopathic Pulmonary Fibrosis

Closed pleural biopsy  ;Open pleural biopsy 

Anatomical Distribution of Pulmonary Disease

Congenital Cystic Adenomatoid  Malformation

Bronchopulmonary Sequestration

Acute Respiratory Distress Syndrome

Neonatal Respiratory Distress Syndrome

Complications of Neonatal Respiratory Distress Syndrome

Sarcoidosis

Extrinsic Allergic Alveolitis 

Pulmonary Eosinophilic Granuloma

Pathological Diagnosis of Granulomatous Lung Diseases

Infectious Granuloma of the Lung

Non-necrotising Granulomatous Inflammation of  the lung

Histopathological Examination of Pulmonary Granulomatous Inflammation

Idiopathic Pulmonary Fibrosis

Usual Interstitial Pneumonia

Non-specific interstitial  pneumonia 

Desquamative interstitial pneumonia 

Respiratory bronchiolitis-interstitial lung disease

Acute interstitial pneumonia (AIP)/organizing diffuse alveolar damage (DAD)

Lymphocytic Interstitial Pneumonia / Follicular Bronchiolitis

Lipid Pneumonia 

Pulmonary Alveolar Proteinosis

Pulmonary Thromboembolism

Other forms of Pulmonary Embolism

Pulmonary Infarction

Pulmonary Hypertension

Pulmonary Collapse 

Pulmonary Edema

Pulmonary Vasculitis

Wegener's Granulomatosis of  the Lung

Churg-Strauss Syndrome 

Microscopic Polyangiitis

Isolated Pulmonary Capillaritis

Necrotizing Sarcoid Granulomatosis

Pulmonary Hemorrhage 

Pneumoconiosis

Silicosis

Asbestosis

Coal Pneumoconiosis

Talcosis

Pulmonary Infection

Influenza 

Cytomegalovirus infection

Respiratory syncytial  virus infection

Measles

Varicella

Chlamydial Infection

Q Fever 

Mycoplasma pneumonia

Pneumococcal Pneumonia (Lobar Pneumonia)

Bronchopneumonia

Klebsiella pneumoniae

Haemophilus influenza Infection

Legionellosis

Staphylococcal Infection

Streptococcal Infection

Tuberculosis

Atypical Mycobacterial Infection

Mycobacterium  Avium Intracellulare

Mycobacterium Kansasii Infection

Histoplasmosis 

Coccidioidomycosis

Cryptococcus

Blastomycosis

Aspergilloma

Aspergillosis

Candidosis

Actinomycosis

Nocardiosis

Pneumocystis Pneumonia

Dirofilariasis

Paragonimiasis      

Reporting of biopsies taken for Inflammatory Skin Diseases

Lichenoid (Interface)Tissue Reaction Pattern

Psoriasiform Reaction Pattern

Vesiculobullous Reaction Pattern

Spongiform Reaction Pattern

Vasculopathic Reaction Pattern

Lichen planus-like lesions

Lichen Nitidus

Bullous Pemphigoid

Dermatitis Herpetiformis

Hailey-Hailey Disease 

Cutaneous Deposits

Calcinosis Cutis

Cutaneous Ossification

Cartilaginous lesions of skin

Lipoid Proteinosis

Gout

Silicone granulomas

Granulomatous Reaction Pattern of the Skin

Granuloma Annulare

Necrobiosis Lipoidica

Necrobiotic Xanthogranuloma   

Rheumatoid Nodule

Lupus Vulgaris

Cutaneous Sarcoidosis

Melkersson Rosenthal Syndrome

Annular Elastolytic Giant Cell Granuloma

Skin lesion in Crohn's Disease

Blastomycosis-like pyoderma

Foreign body granuloma

Rosacea

Interstitial Granulomatous Dermatitis

Interstitial Granulomatous Drug Reaction

Erythema Nodosum

Folliculitis

Impetigo

Furuncle(Boil)

Carbuncle

Toxic Shock Syndrome

Mesothelioma -Online

Aetiology and Pathogenesis of Mesothelioma

Gross features of Mesothelioma

Microscopic features of Mesothelioma

Cytological Diagnosis of Mesothelioma

Histochemistry and Immunohistochemistry in the diagnosis of  Mesothelioma

Variants of  Mesothelioma

WELL DIFFERENTIATED PAPILLARY MESOTHELIOMA

LOCALIZED MALIGNANT MESOTHELIOMA

MULTICYSTIC MESOTHELIOMA

ADENOMATOID TUMOUR

Electron microscopy of  Mesothelioma

Pseudo-mesotheliomatous Adenocarcinoma

Mesothelioma of Atrioventricular Node

                       

Volatile organic solvents and vapors are widely used in industry to dissolve other compounds and as fuels.

 

With few exceptions the exposures are industrial or accidental, and represent acute dangers rather than chronic toxicity.

 

The exposure is mostly by inhalation rather than by ingestion.

Chloroform (CHCl3) and carbon tetrachloride (CCl4) exert anesthetic effects of the central nervous system but are better known hepatotoxins.

With both, large doses lead to acute hepatic necrosis, fatty liver, and liver failure.

Trichloroethylene (Cl2C = CHCl), an  industrial solvent, in high concentrations depresses the central nervous system, but hepatotoxicity is minimal.

There is no evidence for chronic sequelae in man following ordinary long-term industrial exposure.

Methanol (CH3OH) was originally called "wood alcohol" because it was derived from the distillation of wood.

Because the odour and taste of methanol are similar to those of ethanol, it is used by some chronic alcoholics as a substitute for ethanol or by unscrupulous merchants as an adulterant of alcoholic beverages.

In methanol poisoning, inebriation similar to that produced by ethanol is succeeded by gastrointestinal systems, visual dysfunction, coma and death.

The major toxicity of methanol is thought to arise from its metabolism to formaldehyde, principally  by alcohol dehydrogenase, followed by its oxidation to formic acid by aldehyde dehydrogenase.

The most characteristic lesion of methanol toxicity is necrosis of retinal ganglion cells and subsequent degeneration of the optic nerve, a process presumably mediated by the metabolites of methanol oxidation.

Interestingly, methanol-induced blindness occurs only in primates.

It is not clear whether the metabolic acidosis seen in cases of methanol poisoning results from a direct effect of formate or from an inhibition of glucose oxidation.

Gasoline and kerosene are mixture of aliphatic hydrocarbons and branched, unsaturated, and aromatic hydrocarbons.

Despite prolonged exposure to gasoline, gas station attendants, auto mechanics, and so on do not manifest any evidence of toxicity.

The increased use of kerosene as a home heating fuel has led to accidental poisoning of children.

Ethylene glycol (HOCH2CH2OH), commonly used as an antifreeze, has been ingested by chronic alcoholics as substitute for ethanol for many years.

Poisoning with this compound has recently come into prominence because it has been used to adulterate wines in some countries, owing to the sweet taste and solubility.

Like methanol, ethylene glycol is much more toxic in man than in other animals.

The major toxicity related to acute tubular necrosis in the kidney.

Oxalate crystals in the tubules and oxaluria are often noted.

Benzene (C6H6), the prototypic aromatic hydrocarbon, must be distinguished from benzine , a mixture of aliphatic hydrocarbons.

Benzene is one of the most widely used chemicals in industrial processes, being employed as the starting point for innumerable syntheses, as a solvent, and as a constituent of fuels.

Virtually all cases of acute and chronic benzene toxicity have occurred against the background of industrial exposure.

Many instances have been reported in shoemakers and workers in shoe manufacturing ,occupations which at one time were associated with heavy exposure to benzene-based glues.

Acute benzene poisoning primarily affects the central nervous system, and death results from respiratory failure.

However, it is the chronic effects of benzene exposure that have attracted the most attention.

The bone marrow is the principal target in chronic benzene intoxication.

Those who develop hematologic abnormalities characteristically exhibit hypoplasia or aplasia of the bone marrow and pancytopenia.

Aplastic anemia usually is seen while the workers are still exposed to high concentrations of benzene.

In a substantial proportion of cases of benzene induced anemias, acute myeloblastic leukemia or erythroleukemia develops during continuing exposure to benzene or after a variable latent period following removal from the hazardous environment.

Some cases of acute leukemia have occurred without a prior history of aplastic anemia.

While instances of chronic myeloid and chronic lymphocytic leukemia have been reported, a cause-and-effect relationship with benzene exposure is less convincing than with cases of acute leukemia.

The closely related compound toluene, also widely used for its solvent properties, has not been incriminated as a cause of hematologic abnormalities.

Environmental Pathology - Effect of Chemicals: click here

Toxic effect of agricultural chemicals: click here

                         

Multi-organ toxicity and death following acute unintentional inhalation of paint thinner fumes.Clin Toxicol (Phila). 2007;45(3):287-9.

BACKGROUND: Paint thinners containing a mixture of volatile organic solvents have considerable potential for solvent abuse. Deaths from solvent inhalation have been reported but most of them relate to intentional solvent abuse and occur soon after exposure. Accidental death due to unintentional inhalation of solvent vapors can also occur suddenly but more often, death results from late complications secondary to multi-organ toxicity. Malfunctioning of the cardiorespiratory, renal, and central nervous systems as a result of latent-toxic effects of solvent exposure has received little attention. CASE REPORT: An adult male unintentionally inhaled an excessive amount of paint thinner vapors and immediately developed central nervous system effects, followed by severe cardiorespiratory and renal pathologies that ultimately led to death 11 days after exposure. CONCLUSION: Acute unintentional inhalation of paint thinner fumes resulted in serious multi-organ toxicity and death. This case strongly suggests the need to employ suitable precautionary measures while handling volatile organic solvents in a confined area.

Benzene exposure and risk of non-Hodgkin lymphoma.Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):385-91.

Exposure to benzene, an important industrial chemical and component of gasoline, is a widely recognized cause of leukemia, but its association with non-Hodgkin lymphoma (NHL) is less clear. To clarify this issue, we undertook a systematic review of all case-control and cohort studies that identified probable occupational exposures to benzene and NHL morbidity or mortality. We identified 43 case-control studies of NHL outcomes that recognized persons with probable occupational exposure to benzene. Forty of these 43 (93%) studies show some elevation of NHL risk, with 23 of 43 (53%) studies finding statistically significant associations between NHL risk and probable benzene exposure. We also identified 26 studies of petroleum refinery workers reporting morbidity or mortality for lymphomas and all neoplasms and found that in 23 (88%), the rate of lymphoma morbidity or mortality was higher than that for all neoplasms. A substantial healthy-worker effect was evident in many of the studies and a comprehensive reevaluation of these studies with appropriate adjustments should be undertaken. Numerous studies have also reported associations between benzene exposure and the induction of lymphomas in mice. Further, because benzene is similar to alkylating drugs and radiation in producing leukemia, it is plausible that it might also produce lymphoma as they do and by similar mechanisms. Potential mechanisms include immunotoxicity and the induction of double-strand breaks with subsequent chromosome damage resulting in translocations and deletions. We conclude that, overall, the evidence supports an association between occupational benzene exposure and NHL.

Estimating risk during showering exposure to VOCs of workers in a metal-degreasing facility. J Toxicol Environ Health A. 2007 Apr 1;70(7):627-37.

The incremental risk of workers in a metal-degreasing facility exposed to volatile organic compounds (VOCs) present in the water supply during showering was estimated. A probabilistic and worst-case approach using specific-site concentration data and a generalized multipathway exposure model was applied. Estimates of hazard index and lifetime cancer risk were analyzed for each chemical and each route of exposure (inhalation and dermal absorption). The results showed that dermal exposure to trichloroethylene (TCE) and tetrachloroethylene (perchloroethylene, PCE) represented the main contribution to total risk. Although the inhalation route did not produce significant exposure, it was mainly influenced by the liquid flow rate of the shower. Lower values of this parameter during showering resulted in a significant reduction of both carcinogenic and noncarcinogenic risk, while decreasing water temperature produced a minimal effect on exposure by this pathway. The results obtained in the present study indicated that significant exposures of workers may be produced during showering in metal degreasing installations where releases to water of VOCs occur. A sensitivity analysis was developed for investigating the effect of scenario parameters on exposure. Although site-specific data were employed, the exposure of workers was assessed in a model scenario and thus the quantification of risk is associated with uncertainty. Considering that occupational exposure to organic solvents of workers in metal-degreasing facilities may also be significant, risk assessment must be included in the planning of this kind of industrial installation.

Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industries. Part XXX: Causal relationship between chronic myelogenous leukemia and benzene-containing solvents.Ann N Y Acad Sci. 2006 Sep;1076:110-9.

Benzene and benzene-containing products and solvents have long been associated with bone marrow toxicity. Both animal studies and human epidemiological studies have shown statistically significant increases of leukemia and other lymphohematopoietic cancers in workers exposed to benzene. The most common leukemia that has been associated with benzene exposure, also called benzene poisoning, is acute myelocytic leukemia (AML). A review of the epidemiological literature on workers exposed to benzene or benzene-containing solvents and products shows, without question, that this exposure is significantly related to other types of leukemia and lymphoma. In this article, we review the literature on the relationship between benzene exposure and chronic myelogenous leukemia (CML) and find that benzene and benzene-containing products are significantly related to morbidity and mortality from CML.

Formaldehyde as a potential human leukemogen: an assessment of biological plausibility.Crit Rev Toxicol. 2006 Feb;36(2):135-53.

The International Agency for Research on Cancer (IARC, 2004) recently reevaluated the epidemiological data on formaldehyde and concluded that there was "strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to formaldehyde." This conclusion was tempered since a mechanism for leukemia induction could not be identified. Chemically induced leukemia is a well-studied phenomenon with benzene and a number of cancer chemotherapeutic drugs recognized as capable of causing this effect. Abundant in vitro and in vivo data in animals and humans demonstrate that exposure to sufficient doses of these recognized leukemogens can initiate a cascade of events leading to hematopoietic toxicity and the subsequent development of leukemia. This review addresses the biological plausibility that formaldehyde might be capable of causing any type of leukemia by providing a broad overview of the scientific data that must be considered in order to support or refute a conclusion that a particular substance might be leukemogenic. Data on benzene and selected chemotherapeutic cancer drugs are used as examples and are briefly summarized to demonstrate the similar biological events thought to result in leukemogenesis. These data are compared and contrasted with the available data on formaldehyde in order to judge whether they fulfill the criteria of biological plausibility that formaldehyde would be capable of inducing leukemia as suggested by the epidemiological data. Based on the epidemiological data, it is reasonable to expect that if formaldehyde was capable of inducing leukemia, in vivo and in vitro data would offer supporting evidence for biological plausibility. In particular, there is (1) no evidence to suggest that formaldehyde reaches any target organ beyond the site of administration including the bone marrow, (2) no indication that formaldehyde is toxic to the bone marrow/hematopoietic system in in vivo or in vitro studies, and (3) no credible evidence that formaldehyde induces leukemia in experimental animals. As discussed in this review, based on the key biological events that occur in the process of chemically induced leukemia, there is inadequate biological evidence currently available to corroborate existing weak epidemiological associations. This provides an insufficient database to conclude that there is a causal relationship for formaldehyde and leukemia risk.

Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?J Occup Med Toxicol. 2006 Jul 26;1:19.

ABSTRACT: BACKGROUND: Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML). Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. CASE PRESENTATION: Two white females (A and B) hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5). The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3). Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987-1993 and 1997-2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently developed symptoms of respiratory irritation and dizziness. CONCLUSION: The findings support the hypothesis that the specific AML cases might have originated from exposure to chemicals, especially hydroquinone and/or glutaraldehyde. The report also emphasises the crucial role of inspection of facilities and enforcement of compliance with regulations in order to prevent similar incidents.

Study of chemical composition of glue "RAZI" used by solvent abusers in Tbilisi. Georgian Med News. 2006 Apr;(133):65-7.

The analysis of the glue "RAZI" was carried out at the Republican Chromatographic Center of Georgia, with high-efficient liquid chromatographic equipment "Millipore Waters" (USA), by I. Wagner's Method. We were able to determine presumable composition of the glue chemical components. The different substances were evaporated at different times fixed by appropriate peaks on chromatogram. There have been at least five toxic substances identified within the glue composition, which are used as industrial or household chemical goods and as some authors explain, may be used as inhaling psychoactive substances. These substances are: benzol (benzene), toluene (toluol), phenol (carbolic acid), chloroform, and methyl-ketone. The glue is inhaled with a small polyethylene bag. The substances are evaporated during inhalation and join arterial blood through lungs. In several minutes leap forward a situation similar to alcohol intoxication. The evaporated substances characterized by strong toxicity and influence to the organism in different ways. The results of chronic glue abuse is serious, such as lethal aplastic anemia, leukemia, marrow damage, chromosome aberrations, functional disorders of CNS, dystrophic changes in myocardium, cirrhosis, liver atrophy and so on. Abuse of the glue "RAZI" can lead to very serious medical consequences and represents emerging public health problem in Georgia.

Classification of risk occupation for benzene exposure by urine trans, trans-munconic acid level. Asian Pac J Cancer Prev. 2006 Jan-Mar;7(1):149-50.

Leukemogenesis due to benzene exposure is of particular concern because of ongoing exposure to thousands of workers in industrial plants. Monitoring of at-risk workers is recommended and of several biomarkers, urine trans,trans-muconic acid (ttMA) determination is a helpful test. The aim of this work was to classify risk occupation for benzene exposure by urine ttMA level. Here, the author compared exposure risk ratios from 6 previous reports concerning urine ttMA determination. Of interest, the high risk occupations were found to be those which have direct contact with benzene in environmental ambient air, with petroleum fuel as the common source.

Occupational exposure to solvents and the risk of lymphomas.Epidemiology. 2006 Sep; 17(5): 552-61.

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.

Dermal exposure assessment to benzene and toluene using charcoal cloth pads.J Expo Anal Environ Epidemiol. 2005 Jan;15(1):47-50.

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures (maximum 17-fold, P = 0.02) than for inhalation exposures (maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures (maximum 23-fold, P = 0.01) as compared to inhalation exposures (maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the sampler is protected against direct contact and splashes, but still permeable for the gas phase. This design would most likely result in a better ability to correct for airborne concentrations at a given body location.

A field method for sampling toluene in end-exhaled air, as a biomarker of occupational exposure: correlation with other exposure indices.Ind Health. 2004 Apr;42(2):226-34.

A sensitive and rapid method for the determination of toluene in exhaled air is described. We have developed a device for direct breath sampling consisting of a sampler inserted into an empty 58 mL glass vial closed by a Teflon rubber septum. The sorbent cartridge functions as a diffusive sampler and employs a Tenax resin (300 mg, 35/50 mesh) to trap volatile organic compounds from the exhaled air. End-exhaled air is collected "in field" by removing the septum from the vial, by forcibly exhaling into the device through a suitable Teflon tube, and then by sealing the bottle quickly. Environmental toluene levels ranged from 13 to 191 mg/m3, while the concentrations of the solvent in alveolar air, in blood and urine ranged from 159 to 3354 ng/L, from 3.6 to 53.5 microg/L, and from 8.7 to 142.4 microg/L respectively. The correlation coefficients (r) of biological measurements towards environmental toluene levels were 0.822, 0.850 and 0.846 for alveolar air, blood and urine samples, respectively. The breath sampler allowed the rapid and non-invasive collection of data on elimination of toluene.

The endogeneous formation of highly chlorinated tetrahydro-beta-carbolines as a possible causative mechanism in idiopathic Parkinson's disease. Adv Exp Med Biol. 2003;527:253-63.

The causative interrelationship between long-term, low level exposure to chlorinated volatile organic solvents (VOSs) and neurodegenerative diseases (polyneuropathy, encephalopathy) are still an issue of controversial debate. Endogeneously formed chlorinated tetrahydro-beta-carbolines found by Bringmann 1995 (TaClo hypothesis) may contribute, in particular, to the development of (idiopathic) Parkinson's disease (PD) in the presence of the sufficient amount of trichloroacetaldehyde, an intermediate in metabolism of trichloroethylene (TRI). Long-term storage of specific VOSs over years, evident frrom exhalation pattern during the postexposure period, may serve as a promoting factor to form continuously TaClo non-enzymatically from tryptamine and trichloroacetaldehyde. Thus, the induction of TaClo-mediated neurotoxic processes extends over years. The onset of Parkinson's disease in three chronic TRI-exposed individuals during the postexposure period could be associated with the presence of TaClo in ng-range. Consequently, determination of TaClo and its derivatives in blood of humans exposed to chlorinated VOSs may serve as a marker of risk indicating either causative or supportive processes of neurodegeneration that may lead to manifestation of PD after many years.