Mineralstaubgehalt des Lungengewebes und der Lymphknoten bei Eierschalenverkalkungen

Zusammenfassung Der exogene und endogene Mineralgehalt der Lungen und der regionären Lymphknoten von 3 verstorbenen Arbeitern mit Silikose, Eierschalenverkalkungen und Lungensteinen wurde mit Hilfe des Formamidverfahrens isoliert und chemisch sowie mineralogisch untersucht. Die in reifer Form als Hydroxylapatit vorliegenden Verkalkungen werden als Makrolithen oder Eierschalen in den mediastinalen und broncho-pulmonalen Lymphknoten und als Mikrolithen in den Lymphgewebsanteilen der Lunge gebildet. Es besteht eine ausgeprägte Abhängigkeit zwischen der Quarzmenge pro 100 g Trockengewebe und dem Ausma\ der Verkalkungen bzw. der Steinchen-Bildung. Der Transport von Quarz zu den regionären Lymphknoten war au\erordentlich rege, während die Aluminium-, Eisen-, Titan- und Magnesium-Werte im Lungenstaub höher lagen. Der Kohleanteil des Staubes war relativ gering, besonders im Schwielengewebe und in den Lymphknoten.Die Pathogenese dieser eigenartigen, endemisch auftretenden Komplikation der Silikose wird in Verbindung mit möglichen endokrinen Störungen (Hypothyreoidismus) und calciphylaktischen Reaktionen infolge erhöhter Dihydrotachysterolempfindlichkeit und Inhalation von Spurenelementen mit dem Staub (Schwermetalle) erörtert.

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Mineral dust content of the lung tissue and lymph nodes in egg-shell calcification

Summary The exogenous and endogenous mineral content of the lungs and regional lymph nodes of 3 workers who died of silicosis with egg-shell calcification was isolated by formamide decomposition and subjected to chemical and mineralogical analysis. Macroliths or egg-shells are formed in the mediastinal and pulmonary lymph nodes, and microliths in the lymphatic tissue of the lung. All fully developed calcifications consist of hydroxylapatite. There is a distinct correlation between the amount of quartz per 100 g of dry tissue and the degree of calcification or concrement formation. The transportation of quartz to the regionary lymph nodes was extraordinarily intensive, whereas the amounts of aluminium, iron, titanium, and magnesium were found to be greater in the lung dust. The carbon percentage of the dust was relatively low, especially in the callous regions and in the lymph nodes.The discussion deals with the possibility that the pathogenesis of this strange endemic complication of silicosis may be connected either with endocrine disturbances (hypothyroidism in regions were goitre is endemic) with spontaneous rise in serum calcium or calciphylactic reactions resulting from increased sensitivity to dihydrotachysterol and inhalation of trace elements (iron and heavy metals) in the dust.

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Mit Mitteln der Bergbau-Berufsgenossenschaft (Bochum) und des Landes Nordrhein-Westfalen durchgefÜhrte Forschungsarbeit.     

“I never thought I'd make it quite this far”: A personal journey in international understanding

The author provides a brief account of her travel and experiences in several developing countries and explores some of the resulting personal transformations in her attitudes, assumptions and understandings. Persons working with children and youth can learn much from those countries which are economically under-developed, but which retain a simplicity in daily life and a commitment to the central importance of family and community.     

Psychosocial stressors associated with Mexican migrant farmworkers in the midwest United States

Although estimates suggest that there are upwards of 5 million migrant farmworkers in the United States, scant research has explored the stressors associated with their lifestyle. Contrary to previous work, the present study directly explored migrant farmworkers' own perceptions of what is difficult in their lives. The purposes of the present study were to qualitatively explore, from a phenomenological standpoint, the stressors associated with living as a migrant farmworker in the Midwest United States; and to determine the stressors that were most strongly related to symptoms of anxiety and depression. The findings indicated that 18 stressors were commonly experienced by the migrant farmworkers and that the farmworkers experienced overall elevated levels of anxiety and depression. A number of stressors that were not previously reported in the literature were identified. The stressors of rigid work demands and poor housing conditions were significantly associated with higher levels of anxiety and low family income/living in poverty and rigid work demands were significantly associated with depression. Implications of findings and prevention strategies are discussed.     

Improving on‐time performance in health care organizations: a case study

In this paper, we propose a strategy to build a measurement system that helps improve ontime performance in health care organizations. We analyze the measurement system for monitoring the performance of daily start times of first surgeries in a U.S. hospital. Although surgeons appear to be the main cause of delay, efforts to improve their ontime performance alone are not sufficient to improve ontime performance for first surgeries. Therefore, working on the main source of delay to improve performance, as the Pareto principle suggests, does not always work in the health care context. Rather, we found that ameliorating the hospital's overall ontime performance achieves the desired result of improving surgeons' performance through a snowball effect (a selfreinforcing effect) and, consequently, the ontime performance for first surgeries also improves.     

Use of tranquilizers and sleeping pills among cancer patients is associated with a poorer quality of life

To evaluate the association between sleeping pill/tranquilizer (SP/T) use and quality of life (QOL) among cancer patients. Patients and methods: Oncology patients (n=909) in three Israeli hospitals were interviewed in clinics, day centers and in-patient departments regarding SP/T use in the previous week. Crude and adjusted QOL scores, measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30), were compared in users vs. non-users. Results: Sleeping pill/tranquilizer use was self-reported by 234 (25.7%) participants, but rarely documented in medical charts. Factors associated with SP/T use were female gender (adjusted Odds ratio, OR: 1.79; 95% Confidence interval, CI: 1.22–2.62, age (OR: 4.6; 95% CI: 1.66–12.53 for age 70+), place of birth (OR: 1.97; 95% CI: 1.19–3.26 for Eastern Europe compared with Israel), concomitant use of painkillers (OR: 2.88; 95% CI: 1.97–4.20) and presence of cardiovascular disease (OR: 2.41; 95% CI: 1.48–3.91). Controlling these factors as well as disease status, users had a poorer QOL on all functional scales (P<0.001) as well as global QOL. Furthermore, users reported increased severity of symptoms, especially fatigue, insomnia, pain, dyspnea and constipation (P<0.01), compared to non-users. Conclusions: Use of SP/T, reported by one fourth of cancer patients, was associated with substantially poorer QOL and increased severity of symptoms. Causal inference is not possible given the cross-sectional design. Periodic inquiry regarding use of these medications in the Oncology Clinic is recommended since it may identify patients with poor QOL and unmet needs.     

A model for the prevention of iatrogenic disease associated with work-related low back pain

A review of national statistics related to workers' compensation strongly suggests that the current system for managing work-related back pain is not only ineffective but may actually promote disability. It is this author's view that a comprehensive unifying solution exists within the military forward treatment model used to prevent iatrogenic disability in battle fatigue casualties. Because military personnel and employed workers are similarly entitled it is felt that this proven model may likewise be effective in the prevention of iatrogenic disability in the worker with a job-related back injury. The model, acronymed SPICE, includes five components: Simplicity, Proximity, Immediacy, Centrality, and Expectancy.     

Toxicity of mercury,copper, nickel,lead, and cobalt to embryos and larvae of zebrafish,Brachydanio rerio

The toxicity of mercury (HgCl₂), copper (CuCl₂: 5 H₂O), nickel (NiSO₄: 6 H₂O), lead (Pb(CH₃COO)₂: 3 H₂O) and cobalt (CoCl₂: 6 H₂O) was studied under standardized conditions in embryos and larvae of the zebrafish,Brachydanio rerio. Exposures were started at the blastula stage (2–4 h after spawning) and the effects on hatching and survival were monitored daily for 16 days. Copper and nickel were more specific inhibitors of hatching than cobalt, lead, and mercury. Nominal no effect concentrations determined from the dose-response relationships (ZEPs, Zero Equivalent Points) for effect on hatching time were 0.05 g Cu/L, 10 g Hg/L, 20 g Pb/L, 40 g Ni/L and 3,840 g Co/L, and those for effect on survival time were 0.25 g Cu/L, 1.2 g Hg/L, 30 g Pb/L, 80 g Ni/L, and 60 g Co/L. The no effect concentrations for Ni, Hg and Pb are consistent with previously reported MATC values for sensitive species of fish. The no effect concentrations for copper are 1–2 orders of magnitude lower than previously reported values. The major reason for the latter discrepancy was considered to be the absence of organics that can complex copper ions in the reconstituted water that we used, which had a hardness of 100 mg/L (as CaCO₃) and a pH of 7.5–7.7. Unexposed controls were started with embryos from different parental zebrafishes and the parental-caused variability in early embryo mortality, median hatching time and median survival time were estimated.     

Chronic toxicity and bioaccumulation of 2,5,2′,5′- and 3,4,3′,4′-tetrachlorobiphenyl and Aroclor® 1242 in the amphipodHyalella azteca

The addition of 100 (g/L of Aroclor^® 1242 (A1242) or 2,5,2,5-tetrachlorobiphenyl (TeCB) during 10 week chronic toxicity tests withHyalella azteca resulted in complete mortality. There were no effects on survival, growth, or reproduction after addition of 30 g/L. Toxic effects were observed at tissue levels of between 30 and 180 g/g on a wet weight basis, and tissue levels appear to be a better indicator of toxicity than levels in water. No toxic effects were observed after additions of up to 2,700 g/L of the coplanar congener 3,4,3,4-TeCB.H. azteca has the ability to avoid accumulating in excess of 140 g/g 3,4,3,4-TeCB. The amount taken up was proportional to the amount added in water up to 100 g/L, but was constant at higher additions, possibly accounting for its relatively low toxicity. The low toxicity of the coplanar congener, as compared to the non-coplanar 2,5,2,5-TeCB, is in direct contrast to the high toxicity of coplanar PCB congeners to mammals and may be associated with slower rates of aromatic hydrocarbon metabolism in amphipods. Polychlorinated biphenyl levels measured in amphipods from Lake Ontario are approximately 100-fold below levels associated with toxicity inH. azteca, but are above levels which, through biomagnification up the food chain, lead to salmonid residues in excess of 2 g/g, a tolerance limit for human consumption.     

Effects of an Elementary School Intervention on Students' “Connectedness” to School and Social Adjustment During Middle School

This research examined the effects at follow-up during middle school of a comprehensive elementary-school intervention program, the Child Development Project, designed to reduce risk and promote resilience among youth. Parental consent to participate in the middle school study was obtained for 1,246 students from six program and six matched comparison elementary schools. Three of the program elementary schools were in the high implementation group, and three were in the low implementation group during the elementary school study. Findings indicated that, studywide, 40% of the outcome variables examined during middle school showed differences favoring program students, and there were no statistically reliable differences favoring comparison students. Among the high implementation group, 65% of the outcome variables showed differences favoring program students. Overall, program students were more engaged in and committed to school, were more prosocial and engaged in fewer problem behaviors than comparison students during middle school. Program students who experienced high implementation during elementary school also had higher academic performance, and associated with peers who were more prosocial and less antisocial than their matched comparison students during middle school. Implications of these findings for prevention programming are discussed.     

Occupational exposure to fosetyl-Al fungicide during spraying of ornamentals in greenhouses

Eight workers were monitored by the dermal patch/hand rinse technique for exposure to the fungicide aluminum tris-o-ethyl phosphonate [fosetyl-Al or ALIETTE^®] during treatment of ornamentals in a greenhouse, using commercial back-pack sprayers. The mean total dermal exposure for mixers was 512 g a.i./hr and for applicators 389 g a.i./hr. Mixers had higher exposure to the face and neck (213 g/hr) than did applicators (115 g/hr). Workpants provided 4 to 6 times greater protection than workshirts. The highest exposure for both activities was to the forearms. Hand exposure represented only 6% of total exposure, while regions protected by clothing contributed 47% of total exposure for mixers and 60% for applicators. Respiratory exposure contributed 7–9% of total exposure. The high variability in dermal patch results suggests a lack of precision in the sampling methodology, and indicates a need for larger sample sizes.     

Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate

Summary The exposure of 11 pharmaceutical plant workers to methotrexate (MTX) was studied. Personal air samples were taken during the different manufacturing processes: drug compounding, vial filling, and tablet preparation. The uptake of MTX was established by the determination of MTX in urine. MTX was analyzed using the fluorescence polarization immunoassay (FPIA), a method that is frequently used for monitoring serum levels in patients treated with MTX. The FPIA method was modified in such a way that MTX could be measured quickly and efficiently in air and urine samples. MTX was detected in air samples of all workers except for those involved in the vial filling process (range: 0.8–182 g/m³; median: 10 g/m³). The highest concentrations were observed for workers weighing MTX (118 and 182 g/m³). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72–96 h was 13.4 g MTX-equivalents (range: 6.1–24 g MTX-equiva g MTX-equivalents (range: 6.1–24 g MTX-equivalents). lents). A significantly lower background level of 10.2 g A significantly lower background level of 10.2 g MTX-equivalents was measured in urine of 30 control persons (range: 4.9–21 g MTX-equivalents).     

Comprehensive pediatric primary care vs traditional care in an israeli population: Their influence on pediatric emergency room use and hospitalization

Emergency room (ER) utilization and hospitalization were studied as indicators of the impact of improvements in pediatric primary care services in an Israeli development town, Ofakim, population 12,000. One of the two pediatric services was upgraded in 1976 through the introduction of pediatric faculty, integration of preventive and curative services and conversion of the medical records to a problem-oriented format ( experimental clinic B ). The primary care system remained unchanged in the second clinic ( traditional clinic A ). During 1980, ER utilization by the B clinic population was 9.3/100 compared with 17.6/100 for the A clinic population. Fifty two percent of the B clinic population patients reaching the ER were hospitalized compared with 25% of A clinic patients.The lower ER utilization rate represents a significant saving for the health services, and educational interventions are suggested from the study. Analysis of ER utilization data seems to offer useful information for overall planning and monitoring of ambulatory services for a community.Corresponding author.     

The Po River Delta epidemiological survey: Reference values of total serum IgE levels in a normal population sample of North Italy (8–78 yrs)

The aim of this paper was to define, for the first time in Italy, normal levels of total serum IgE in a general population sample of North Italy. Total serum IgE in 1905 subjects, living in Po Delta area (near Venice), were measured by PRIST method. Normal values were derived from 558 subjects without asthma and/or asthmatic/rhinitic symptoms, noncurrent smokers, skin prick-test negatives (normals). Cut-off values to differentiate normals from the remaining part of the sample (others), from asthmatic, and from rhinitic subjects, were established with the IgE value midway between the upper limit of the 95% confidence intervals (CI) of the geometric mean for normals and the lower limit for others, asthmatics, and rhinitics, respectively. Geometric mean of normal children–adolescents was 45 kU/L (SD: 2.6; 95% CI: 38–63). In normal adults geometric mean was 29 kU/L (SD: 3.3; 95% CI: 25–40) in males and 19 kU/L (SD: 3.8; 95% CI: 16–22) in females. The diagnostic sensitivity of IgE test was low, while the specificity was very high. A good positive predictive value in discriminating normals from others was found, on the contrary, we found a good negative predictive value in discriminating normals from asthmatics or from rhinitics. In conclusion, our results confirm that it is necessary to provide separate total serum IgE reference values for what concerns age in children–adolescents and in adults, and gender, in adults. Low level of total serum IgE are helpful to exclude allergic asthma or rhinitis.     

Inter and intea-observer variation in ultrasonographic detection of gallstones: The Multicenter Italian Study on Epidemiology of Cholelithiasis (M.I.COL.)

Inter and intea-observer agreement in classifying the presence of gallstones by ultrasonographic images according to established criteria was studied. A film recording of 50 routine ultrasonographic examinations of the gallbladder was read by each of the 46 observers who participated in the Multicenter Italian Study on Epidemiology of Cholelithiasis (M.I.COL.). The overall Kappa score for inter-observer agreement was 0.649, while intea-observer agreement was good or excellent (Kappa scores >0.60) in 75% of the observers. No statistical difference for inter-observer agreement between novices and expert echographers was found in the overall Kappa statistic or in category-specific Kappa scores (gallstone, no gallstone, doubtful and inconclusive examinations) The present study suggests that the development of explicit criteria by a group of trained echographers does not eliminate inter-and intea-observer disagreement in categorizing subjects for gallbladder stones. M.I.COL. (Multicentrica Italiana Colelitiasi).Corresponding author.See appendix.     

Determinants of household health expenditure on western institutional health care

We try to identify determinants of illness reporting, provider choice and resulting expenditure with different econometric models using data from a representative household panel survey of 800 households in Nouna health district, Burkina Faso, during 2000–2001. The factors being an adult, married, illness occurred in rainy season and severe illness significantly increased the magnitude of health expenditure. Compared to malaria, individuals spent more on other infectious diseases, injury and the other disease category. In contrast, people were less likely to spend on chronic illness. An individual who belonged to a household headed by a female, a literate household head and with a higher household expenditure had a significantly positive association with the magnitude of expenditure. Findings from this study can be used for policy implication to improve health system performance in Burkina Faso through enhancing health care utilization.     

Short-term exposure of zooplankton to the synthetic pyrethroid,fenvalerate, and its effects on rates of filtration and assimilation of the alga,Chlamydomonas reinhardii

In acute tests of toxicity, two cladocerans,Daphnia galeata mendotae andCeriodaphnia lacustris, and the calanoid,Diaptomus oregonensis, were more sensitive to fenvalerate thanDaphnia magna, the organism used in standard laboratory bioassays. The 48-hr EC₅₀s for each species/stage in order of increasing sensitivity were adultD. magna — 2.52 g/L;D. magna (48-hr old) — 0.83 g/L; adultD. galeata mendotae — 0.29 g/L; adultC. lacustris — 0.21 g/L;D. galeata mendotae (48-hr old) — 0.16 g/L; adultDiaptomus oregonensis — –0.12 g/L. No toxicity was observed when these organisms were exposed to a range of concentrations of the emulsifiable concentrate without fenvalerate (the EC blank).Rates of filtration of the¹⁴C-labelled alga,Chlamydomonas reinhardii byD. galeata mendotae, C. lacustris andD. oregonensis were decreased significantly at sublethal concentrations of fenvalerate after only 24-hr exposure.Ceriodaphnia lacustris showed the greatest sensitivity with rates of filtration significantly decreased at 0.01 g fenvalerate/ L. Concentrations of fenvalerate 0.05 g/L resulted in decreased rates of filtration byD. galeata mendotae. A concentration of 0.10 g fenvalerate/ L caused rates of filtration to increase inD. oregonensis. whereas 0.05 and 0.5 g/L resulted in a decrease in these rates.Rates of assimilation of algae byD. galeata mendotae, C. lacustris andD. oregonensis exposed to similar concentrations of fenvalerate were decreased at concentrations 0.05 g fenvalerate/L. Changes in rates of assimilation were not as sensitive a parameter of toxicity as changes in rates of filtration. The EC blank had no significant effects on rates of filtration or assimilation for all three species.     

An evolutionary perspective of sex-typed toy preferences: pink,blue, and the brain

Large sex differences in children's toy preferences are attributed to gender group identification and social learning. The proposal outlined in this paper is that contemporary conceptual categories of masculine or feminine toys are also influenced by evolved perceptual categories of male-preferred and female-preferred objects. Research on children exposed prenatally to atypical levels of androgens and research on typically developing infants suggest sex-dimorphic preferences exist for object features, such as movement or color/form. The evolution and neurobiology of mammalian visual processing—and recent findings on sex-dimorphic toy preferences in nonhuman primates—suggest further that an innate bias for processing object movement or color/form may contribute to behaviors with differential adaptive significance for males and females. In this way, preferences for objects such as toys may indicate a biological preparedness for a masculine or feminine gender role—one that develops more fully as early perceptual preferences are coupled with object experiences imposed by contemporary gender socialization.     

Die Silikoantimonose

Zusammenfassung a) Da wir den modifizierten Typ der Silikose Zajaa, den wir bei unseren Antimonhüttenarbeitern festgestellt haben, durch Inhalation eines Produktionsstaubes entstehen sahen, der eine hohe Antimonoxyd-Gehalt (über 90%) und und einen ganz geringfügigen silikogenen Staubgehalt (bis 11,5%) aufweist, haben wir diese Abart der Mischstaubsilikose als Siliko-Antimonose bezeichnet und als berufsspezifischen Silikosetyp hervorgehoben, der durch einen Produktionsstaub verursacht wird, der sich nach mineralogischen und chemischen Eigenschaften vom Produktionsstaub sonstiger Herkunft bei anderen Berufen oder anderen Antimonbergwerken, in unseren Falle bei Grubenarbeitern des Antimonerzbergwerks, unterscheidet. Bei Hüttenarbeitern entwickelt sich die Silikoantimonose nach längerer Exposition und schreitet langsamer fort, als dies bei den Bergarbeitern der Fall ist. Komplikationen mit Tuberkulose treten auch bei der Silikoantimonose auf — siehe Röntgenogramme Nr. 3—1957, 3a, 3b—1959.b) Im Sinne des Klassifikationsschemas Sydney 1950 können wir diesen Silikoantimonose-Typ der Klasse Pn. simplex mikronodulärer oder nodulärer Form zuordnen. Massiv-progressive Fibrosen haben wir im pinhead-Material, das von Hüttenarbeitern stammt, noch nicht feststellen können. Es wird dies unsererseits den Gegenstand weiterer Forschungen und Betrachtungen der Entwicklung der Silikoantimonose bei unseren Hüttenarbeitern bilden, bei denen Silikoantimonose des Typs Pn. simplex der 3 p, 3 pm oder 3 pmn-Form auftritt.c) Zeichen allgemein-toxischer Wirkung des Produktionsstaubs mit hohem Sb-Oxyd- und weit geringerem As- und Pb-Gehalt sind in der Hütte bisher nicht verzeichnet worden.d) Um eine volle Klarheit über das Krankheitsbild zu gewinnen und weiterhin die Entwicklung der pneumokoniotischen Veränderungen der Silikoantimonose bei unseren Hüttenarbeitern verfolgen sowie die allgemein toxische Wirkung des Produktionsstaubs, der einen hohen Prozentsatz von Antimonoxyd mit kleinen As- und Pb-Zusätzen hat, bestätigen oder ausschließen zu können, hat unser Institut planmäßige, sowohl in den Betriebsstätten als auch klinisch und toxikologisch vorgenommene Untersuchungen durchgeführt.Mit 11 Textabbildungen     

Bioaccumulation and toxicity of selenium in Chironomus decorus larvae fed a diet of seleniferous Selenastrum capricornutum

The bioaccumulation and toxicity of selenium in a simple aquatic food chain was investigated by feeding a diet of seleniferous algae (Selenastrum capricornutum) to fourth instar midge (Chironomus decorus) larvae. Treatment diets consisted of S. capricornutum cultured in three concentrations of selenite (0, 10, and 40 g Se/L) and four concentrations of selenate (0, 4, 10, and 40 g Se/L). The seleniferous algae was freeze-dried and utilized as a diet for the midge larvae. The data show that, under laboratory conditions, a 96 h dietary exposure of 2.11 g Se/g dry weight significantly reduced larval growth at tissue concentrations 2.55 g Se/g dry weight. The results demonstrate that some invertebrates are very sensitive to dietary selenium exposure. When compared to similar studies with Daphnia magna, the data suggest that invertebrate primary consumers differ in the metabolism of dietary selenium.     

Bromacil and diuron herbicides: Toxicity,uptake, and elimination in freshwater fish

Fathead minnows, 30 days old, were exposed to technical grade bromacil and diuron in flow-through tests to determine acute toxicity. LC₅₀ values for bromacil were 185, 183, 182 and 167 mg/L at 24, 48, 96, and 168 hr, respectively; and for diuron, 23.3, 19.9, 14.2, and 7.7 mg/L at 24, 48, 96, and 192 hr, respectively. Eggs, newly hatched fry, and juvenile fish were continuously exposed to lower concentrations of the herbicides for 64 days. Growth was significantly reduced (p 0.01) at the lowest bromacil exposure of 1.0 mg/L. Therefore, it was not possible to determine a no effect concentration. The no effect concentration for diuron was 33.4 g/L, while the lowest concentration which resulted in adverse effects was 78.0 g/L. Adverse effects at 78.0 g/L were an increased incidence of abnormal or dead fry immediately after hatch (p 0.01) and decreased survival throughout the exposure period (p 0.05). Neither herbicide accumulated significantly in fish tissue, as bioconcentration factors were <3.2 and 2.0 for bromacil and diuron, respectively. Rainbow trout (Salmo gairdneri) injected with radiolabeled bromacil or diuron eliminated over 90% of the radioactivity within 24 hr. Parent compound and metabolites were detected in the aquarium water in both cases. Metabolites of diuron recovered from the water included 3,4-dichloroaniline and several demethylated products.