Is it all in the hinge? A kryptoracemate and three of its alternative racemic polymorphs of an aminonitrile.

Four polymorphs of 2-(perfluorophenyl)-2-(phenylamino)acetonitrile have been crystallized and structurally analyzed: in addition to three racemic crystals, a rare kryptoracemate has been obtained. The central single bonds allow for conformational flexibility: the kryptoracemate as well as two of the remaining polymorphs contain several independent molecules with different conformation. In contrast to these uncommon packing modes, the fourth phase is unexceptional and crystallizes with a single molecule in the asymmetric unit. Individual crystallization batches may contain several crystal forms concomitantly.

Terpenols as substituents for the diastereoselective formation of enantiomerically pure triple lithium-bridged helicate type-coordination compounds.

The terpenols l(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters -H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(iv) triscatecholate helicates Li[Li3()6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[()3Ti]. The equilibrium is studied by (1)H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric α-chiral derivatives Li[Li3()6Ti2] is opposite to the configuration of the monomers Li2[()3Ti]. For the γ-chiral complex Li2[()3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible.

[Necrotizing sialometaplasia--a specific differential diagnosis of an ulcer of the hard palate]. / Die nekrotisierende Sialometaplasie--die besondere Differenzialdiagnose einer Neubildung in der Mundhöhle.

BACKGROUND: Ulcers of the hard palate are mostly caused by malignancies. In addition, rare diseases should be included in the differential diagnosis. Beside specific inflammations (lues, tuberculosis) necrotizing sialometaplasia belongs to these uncommon medical conditions. PATIENTS: A 51-year-old male was admitted to the hospital with an algetic ulcer of the hard palate. Malignancy was ruled out by pathohistological examination. Inflammation or infection was excluded by serological examination. A second biopsy was investigated by the pathologist suspecting necrotizing sialometaplasia and confirmed the suspicion. By applying local treatment and systemic antibiosis against bacterial superinfection the ulcer finally healed. CONCLUSIONS: Necrotizing sialometaplasia is a rare medical condition generated by local circulatory disorder. 128 cases were published so far. Typical patients are males aged 50 and above. Characteristics of this ulcer are a high rate of spontaneous healing and lacking malignancy. After excluding a malignant tumor this rare disease has to be considered when diagnosing an ulcer of the hard palate.

[Paraneoplastic pityriasis rubra pilaris in metastatic adenocarcinoma without diagnosable primary]. / Paraneoplastische Pityriasis rubra pilaris bei metastasiertem Adenokarzinom ohne lokalisierbares Primum.

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman, without a history of severe illness, developed an erythematosquamous skin disease on hands and forearms. After continued spreading of these cutaneous lesions, she was admitted to hospital, presenting with a generalised desquamating erythrodermia and marked pruritus. INVESTIGATIONS: Skin biopsy showed cornocutaneous signs with alternating ortho- and parakeratosis, typical for pityriasis rubra pilaris. Laboratory findings showed a chronic to acute inflammation with leukocytosis, granulocytosis in the differential blood count, raised C-reactive protein in a range from 54.7 to a maximum of 157.2 mg/l and a protein electrophoresis with elevated alpha1- and alpha2-fraction. TREATMENT AND COURSE: The erythrodermia only temporarily receded under systemic therapy with acitretin and prednisolone. The patient developed intermittent septic fever accompanied by reduction or loss of consciousness. The general condition of the patient worsened considerably. Out of a rapidly progressing pleural effusion malignant cells similar to adenocarcinoma were isolated. Because CA15-3 was elevated we conducted an extended search especially for a breast carcinoma, but found only pathologically enlarged axillary, mediastinal and abdominal lymph nodes in conventional X-ray, CT, ultrasound and endoscopic procedures. The patient died from paraneoplastic pulmonary embolism. At autopsy, the widespread metastatic dissemination from poorly differentiated adenocarcinoma was confirmed. A necrosis in the right breast containing tumour cell remnants could probably be regarded as the primary neoplasm. Immunohistochemically no definite proof of breast nor gastro-intestinal carcinoma could be found. CONCLUSIONS: This case presents a rare paraneoplastic cutaneous manifestation as pityriasis rubra pilaris triggered by a poorly differentiated adenocarcinoma. The primary neoplasm could not definitely be identified, neither pre nor post mortem.

An updated mortality study of workers at a petroleum refinery in Beaumont, Texas, 1945 to 1996.

The present investigation represents an update of a previous cohort mortality study of 7543 workers who were employed at a petroleum refinery in Beaumont, Texas, for at least 1 year between 1945 and 1996. The updated study covered an observation period of 51 years, from 1946 to 1996, with a total of 208,627 person-years of observation. A total of 3020 (40.0%) cohort members were known to have died. The mortality data were analyzed in terms of cause-specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). The overall mortality of the cohort was significantly lower than expected when compared with that of the general US population (SMR, 95.7; 95% CI, 92.3 to 99.2). Overall cancer mortality was also lower than expected (SMR, 85.8; 95% CI, 79.4 to 92.5). For specific cancer sites, significant mortality deficits were observed for the following: buccal cavity and pharynx, esophagus, large intestine, rectum, larynx, lung, and bladder and other urinary organs. No significant increase was reported for any site-specific cancer. A non-significant increase in acute myeloid leukemia was observed among male employees (SMR, 147.2; 95% CI, 76.1 to 257.2). Detailed analyses indicated that the excess was restricted to workers hired before 1950. No increase was detected for other leukemia cell-types, non-Hodgkin's lymphoma, or multiple myeloma. For non-malignant diseases, the majority of SMRs were below 100, and no significant increase was observed for any cause. In particular, significant mortality deficits were reported for ischemic heart disease (SMR, 91.0; 95% CI, 85.4 to 96.9), non-malignant respiratory disease (SMR, 61.5; 95% CI, 52.2 to 72.0), pulmonary fibrosis (SMR, 51.0; 95% CI, 22.0 to 100.4), cirrhosis of the liver (SMR, 47.2; 95% CI, 30.6 to 69.7), and accidents (SMR, 81.7; 95% CI, 66.3 to 99.6). Separate analyses of male workers by job classification (process and maintenance) were conducted. Mortality from acute myeloid leukemia was elevated among employees in maintenance jobs (8 observed deaths vs 4.31 expected; SMR, 185.5; 95% CI, 80.1 to 365.6). However, no upward trend by length of service was found. A detailed analysis indicated that the acute myeloid leukemia mortality excess was limited to maintenance workers who were hired before 1950. No other significant excess was detected for any cause among maintenance or process workers. These findings from the present study were discussed in conjunction with results from previous investigations of employees at the Beaumont refinery and with results from other refinery studies. Potential limitations of the study were also discussed.

Updated mortality study of workers at a petroleum refinery in Torrance, California, 1959 to 1997.

The updated cohort consisted of 3328 workers who were employed at the Mobil (now ExxonMobil) Torrance, California, refinery for at least 1 year between 1959 and 1997. The vital status of the cohort was determined through a variety of sources, including company employment or retirement records, the Social Security Administration's Death Master File, and the National Death Index. The updated study covered an observation period of 38 years from 1960 to 1997, with a total of 60,612 person-years of observation. A total of 705 (21.2%) cohort members were identified as having died. Mortality data were analyzed in terms of cause-specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs), with expected deaths based on US national cause-, gender-, race-, year-, and age-specific mortality rates. The overall mortality of the cohort was significantly lower than expected when compared with the US general population (SMR, 81.9; 95% CI, 76.0 to 88.2). Overall cancer mortality was also lower than expected (SMR, 79.8; 95% CI, 67.9 to 93.1). For specific cancer sites, significant mortality deficits were observed for cancer of the digestive system (SMR, 70.9; 95% CI, 49.4 to 98.6) and cancer of the respiratory system (SMR, 74.1; 95% CI, 55.5 to 97.0). No significant increase was reported for any site-specific cancer. For nonmalignant diseases, no significant increase was observed for any cause. In particular, significant mortality deficits were reported for ischemic heart disease (SMR, 87.7; 95% CI, 77.2 to 99.3), chronic endocardial disease and other myocardial insufficiencies (SMR, 8.3; 95% CI, 0.2 to 46.0), all other heart disease (SMR, 64.2; 95% CI, 43.0 to 92.2), and influenza and pneumonia (SMR, 59.2; 95% CI, 33.1 to 97.6). Detailed analysis by length of employment did not reveal any significant mortality excess or upward trend. Analyses of male employees by job classification (process and maintenance) were conducted. Among maintenance workers, mortality from cirrhosis of the liver (SMR, 190.1; 95% CI, 101.2 to 325.1) and suicide (SMR, 208.6; 95% CI, 111.1 to 356.7) were significantly elevated. However, these mortality excesses did not seem to be related to employment at the refinery. No other causes of death showed significant increase among maintenance workers. A similar separate analysis was conducted for process workers, and no significant excess was detected for any cause. The findings from the present study are discussed in conjunction with results from previous investigations of employees at the Torrance refinery and with results from other refinery studies. Potential limitations of the study are also discussed.

A critical review of cancer epidemiology in the petroleum industry, with a meta-analysis of a combined database of more than 350,000 workers.

In 1989 we published a critical review of cancer epidemiology in petroleum workers, which included as a component of the review a meta-analysis by cancer site. Subsequently we have completed three additional reviews and meta-analyses on cell-type-specific leukemias (1995), multiple myeloma (1997), and non-Hodgkin's lymphoma (2000). The objective of the present investigation was to update our 1989 review and meta-analysis of nonlymphohematopoietic cancers in cohort studies of petroleum workers. Included in the present investigation were cohort studies of petroleum workers from the United States, the United Kingdom, Canada, Australia, Finland, Sweden, and Italy. Individual studies were reviewed with regard to specific cancer sites. For each cancer of interest, risk ratios from the individual studies were presented. In some studies, subcohort analyses stratified by exposure parameters such as length of employment, job category, and hire year were also reported. These subcohort or stratified analyses were reviewed and the results of these analyses were taken into consideration in our interpretation. In addition to the qualitative review of individual studies, a meta-analysis was performed to combine data from individual cohort studies of petroleum workers. The primary purpose of the meta-analysis was to provide a summary measure of risk for each cancer site. Based on a review and meta-analyses of cohort studies of more than 350,000 petroleum workers in the United States, the United Kingdom, Canada, Australia, Finland, Sweden, and Italy, we concluded that there was no increased mortality from digestive cancers (stomach, large intestine, liver, or pancreas), lung cancer, bladder cancer, kidney cancer, or brain cancer. The summary standardized mortality ratios for these cancer sites were all below unity. Significant increases of melanoma mortality were reported in some small groups of refinery workers in the United Kingdom and upstream operation workers in Canada, but no responsible agent(s) had been identified. The observed mortality from skin cancer in all other studies was similar to the expected. In particular, no significant increase of skin cancer mortality was reported in any of the U.S. studies. Elevated mortality from prostate cancer was noted in short-term workers at a U.S. refinery and in short-term workers employed in certain crafts at U.S. crude oil operations. However, the absence of an upward trend by length of employment in these workers argued against an association between exposure to petroleum products and prostate cancer. For all petroleum workers as a whole, mortality from prostate cancer was as expected.

Non-Hodgkin's lymphoma and exposure to benzene in a multinational cohort of more than 308,000 petroleum workers, 1937 to 1996.

Petroleum workers are exposed to benzene or benzene-containing petroleum products. As such, studies of these workers provide an opportunity for investigating the relationship between benzene and non-Hodgkin's lymphoma (NHL). However, few cohort studies of petroleum workers report results of NHL separately. One reason is that NHL is usually grouped with other lymphopoietic cancers in the analysis. Another reason is the relatively small number of NHL cases in some studies. To determine the risk of NHL in petroleum workers, we identified 26 cohorts of petroleum workers in the United States, the United Kingdom, Canada, Australia, Italy, and Finland. Authors of the original studies were contacted, and data on the number of observed deaths and person-years of observation were requested. Data from these studies were reviewed individually as well as combined in a pooled analysis (meta-analysis). In particular, results for individual cohorts, most of which had never been reported before, were presented. The combined multinational cohort consisted of more than 308,000 petroleum workers (6.6 million person-years), and the observation period covered an interval of 60 years from 1937 to 1996. A total of 506 NHL deaths were observed, compared with 561.68 expected. The standardized mortality ratio was 0.90 and the 95% confidence interval was 0.82 to 0.98. Analyses were performed by type of facility and industrial process. Stratum-specific standardized mortality ratios (95% confidence intervals) were 0.96 (0.86 to 1.07) for US refinery workers, 1.12 (0.90 to 1.37) for non-US refinery workers, 0.64 (0.50 to 0.82) for product (gasoline) distribution workers, and 0.68 (0.47 to 0.95) for crude oil workers. When individual cohorts were stratified by length of observation, no pattern was detected. In general, exposure levels before 1950 were much higher than thereafter. However, analysis of workers by hire date (< 1950, > or = 1950) revealed no difference in NHL mortality. Furthermore, none of the individual studies showed significant exposure-response relations. In summary, results from individual studies, as well as from the pooled analysis, indicated that petroleum workers were not at an increased risk of NHL as a result of their exposure to benzene or other benzene-containing petroleum products in their work environment. This conclusion was supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of NHL and occupational exposures.

A framework for addressing health issues in or near a manufacturing facility.

Clustering of health events in or around industrial facilities sometimes leads to worker and community concerns that plant management or local health professionals must address. We provide an eight-step process to deal with these concerns systematically. We emphasize the use of good scientific practices with managerial oversight for effective worker and community communication. This process is directed to plant management and the local health professional and emphasizes the practical aspects of the investigation.

Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.

BACKGROUND: An excessive rate of cardiac death is a well-known feature of renal failure. Coronary heart disease is frequent and the possibility has been raised that the natural history of the coronary plaque is different in uraemic patients. We assessed the morphology of coronary arteries in patients with end-stage renal failure and compared them with coronary arteries of matched non-uraemic control patients. METHODS: Fifty-four cases were identified at autopsy who met the inclusion criteria: cases, end-stage renal disease (n=27); controls, non-renal patients with coronary artery disease (n=27). At autopsy all three coronary arteries were prepared at corresponding sites for investigations: (i) qualitative analysis (after Stary), (ii) quantitative measurements of intima and media thickness (by planimetry), (iii) immunohistochemical analysis of the coronary plaques and (iv) X-ray diffraction of selected calcified plaques. RESULTS: Qualitative analysis of the coronary arteries showed significantly more calcified plaques of coronary arteries in patients with end-stage renal failure. Plaques of non-uraemic patients were mostly fibroatheromatous. Media thickness of coronary arteries was significantly higher in uraemic patients (187+/-53 microm vs 135+/-29 microm in controls) and intima thickness tended to be higher (158+/-38 microm vs 142+/-31 microm) but this difference was not statistically significant. Plaque area (4.09+/-1. 50 mm(2) vs 4.39+/-0.88 mm(2)) was comparable in both groups. Lumen area, however, was significantly lower in end-stage renal patients. Immunohistochemical analysis of the cellular infiltrate in coronary arteries showed no major differences in these advanced plaques of uraemic and non-uraemic subjects. CONCLUSION: Coronary plaques in patients with end-stage renal failure are characterized by increased media thickness and marked calcification. In contrast to the previous opinion the most marked difference compared to non-uraemic controls does not concern the size, but the composition of the plaque. Deposition of calcium within the plaques may contribute to the high complication rate in uraemic patients.

A case-control study of lung cancer among refinery workers.

This case-control study examined the relationship between lung cancer and the work histories of male employees at a large Texas refinery. The study included 112 lung cancer deaths observed between 1946 and 1987 and 490 matched controls. Employment histories were obtained from personnel records, and smoking information was available from medical records. Both stratification methods and conditional logistic regression were used in data analyses. Overall employment in four general job categories (administrative, engineering/laboratory, process, maintenance/mechanical) was not associated with lung cancer mortality. Results by hire period (< 1940, 1940+) showed that workers hired into process jobs before 1940 had a nonsignificantly elevated odds ratio (OR) of 1.71 (95% confidence interval [CI] = 0.85-3.45) compared with nonprocess workers hired before 1940. Among process workers hired before 1940, there was a significant trend toward increasing OR with increasing duration of employment in process jobs, and the association with lung cancer was strongest among smokers in the highest duration category of 30+ years (OR = 2.98, 95% CI = 1.07-8.31). Latency analyses of process workers hired before 1940 indicated that their lung cancer risk had peaked between 30 and 50 years since first employment. Definitive statements about causal factors are limited because results among process workers were based on small numbers of subjects in some exposure categories, and there was no information on specific workplace exposures. The OR for maintenance/mechanical jobs after adjustment for smoking was 1.00 (95% CI = 0.55-1.82). Furthermore, there was no pattern in relation to duration of employment in maintenance/mechanical jobs. The results from this study do not support the hypothesis that work in maintenance/mechanical jobs increases lung cancer risk. On the basis of analyses in this study, it is unlikely that asbestos exposure contributed to excess lung cancer mortality. Additional analyses were conducted for specific maintenance jobs with potential exposure to asbestos and by duration in jobs with occasional or routine asbestos exposure. No significant increase in lung cancer was found in any subgroup. Furthermore, there was no significant trend toward lung cancer risk in relation to duration of employment in jobs with asbestos exposure.

[Problems in diagnosis and therapy of juxtapapillary, tubulovillous adenoma]. / Probleme in der Diagnostik und Therapie des juxtapapillären, tubulovillösen Adenoms.

UNLABELLED: Tubulovillous adenoma of the duodenum have a high potential for malignant transformation. An exact preoperative staging and an accurate histological examination are essential in order to choose a proper therapeutic strategy. We report on difficulties in the diagnostic and therapeutic process of a patient with a tubulovillous, juxtapapillary, duodenal adenoma. The adenoma had been resected by means of submucosal excision after infiltrative growth had been excluded endosonographically and malignancy had been ruled out by the histological examination of a taken biopsy. Furthermore no malignant changes had been found in the resected material. However an early recurrence of the tumor questioned the correctness of the first diagnosis. In fact, a retrospective histological examination of the resected specimen revealed an adenocarcinoma, which had been overlooked primarily. Finally the patient underwent duodenopancreatectomy and remains without signs of tumor recurrence so far. CONCLUSIONS: 1. Microinvasion of the submucosa can not be excluded endosonographically. Therefore endosonography can not specify the dignity of an unknown tumor with a sufficient safety, especially if there is only an intramural growth of the tumor without transmural spread. 2. Because of high recurrence rates and a distinct frequency of malignant transformation of duodenal adenomas, a submucosal resection should only be performed in high-risk patient. 3. In that patients the resected material has to be examined as accurately and subtly as possible to rule out a submucosal microinvasion. 4. Based on the above mentioned radical surgery (duodenopancreatectomy) should be performed in all normal risk patients with juxtapapillary adenomas.

Asymmetric Synthesis of Novel Ferrocenyl Ligands with Planar and Central Chirality.

A stereogenic center at the position beta to the metallocene backbone is present in ferrocenyl ligands 2, which are interesting for asymmetric catalysis. These planar-chiral compounds are accessible for the first time by a highly diastereoselective and enantioselective synthesis (de=93-97 %; ee>/=96 %) from the ferrocenyl ketones 1. A variety of donor groups (E(1)=Ph(2)P small middle dotBH(3), SMe, SiPr; E(2)=SMe, STol, SePh, Ph(2)P small middle dotBH(3), iPr(2)P small middle dotBH(3)) can be introduced as electrophiles. Tol=tolyl=CH(3)C(6)H(4).

[Value of endosonography in diagnosis of diffusely growing stomach carcinomas]. / Wertigkeit der Endosonographie in der Diagnostik diffus wachsender Magenkarzinome.

The diagnosis of diffuse type gastric carcinoma is very difficult. The delay of diagnosis is often due to false-negative endoscopic and histologic evaluation. The architecture of the stomach can be clearly visualized by endosonography. Therefore, already minor destructions of the gastric layers can be found. The endosonographic picture includes the presence of the layers, which are larger and of irregular contour. In infiltrating gastric cancer typically the submucosal layer and the muscularis are concentrically enlarged and appear folded. Based on the endosonographic picture diffuse type gastric carcinoma has been diagnosed in 32 patients. When compared to the histologic diagnosis after gastrectomy or autopsy the accuracy of the endosonographic diagnosis was 87.5%, (28 out of 32 patients). From the remaining four patients diagnosed to have diffuse type gastric cancer by endosonography three patients turned out to have malignant infiltrating tumors of different histologies. Therefore, the positive predictive value of endosonography in detection of infiltrating malignant tumors was 96.8% in our group. In contrast the accuracy of preoperative histologic diagnosis by biopsies was only 58%. Suspicious results of gastroscopy, especially in combination with a negative biopsy, should lead to further evaluation by endosonography to detect diffuse type gastric cancer earlier.

An updated mortality study of workers at a petroleum refinery in Beaumont, Texas.

The mortality experience of 7,119 workers who were employed at a Beaumont, Texas, refinery for at least 1 year between 1945 and 1987 was investigated. Mortality analyses based on standardized mortality ratios (SMRs) and 95% confidence intervals (95% CI) showed overall mortality was significantly lower than expected compared with the U.S. general population (SMR = 82, 95% CI = 79-86). Total cancer mortality was also lower than expected (SMR = 92, 95% CI = 84-100). Significant mortality deficits from several malignant and nonmalignant diseases were reported. A significant mortality increase in the broad category of lymphatic and hematopoietic cancers was found (SMR = 133, 95% CI = 103-170). This increase was attributed to a nonsignificant elevation in leukemia of all cell types combined (SMR = 139, 95% CI = 92-201) and a borderline significant increase in other lymphatic tissue cancer (SMR = 158, 95% CI = 101-235). The elevation in leukemia was confined to workers hired before 1950. Furthermore, the leukemia excess was shown to have peaked during the 1960s, with mortality no longer elevated post-1980. Analyses of cell type-specific leukemias showed a similar temporal pattern for acute myeloid leukemia (AML) which was not significantly elevated (SMR = 136, 95% CI = 59-268). Mortality from other leukemia cell types was similar to or lower than expected. Mortality from non-Hodgkin's lymphoma (NHL) (SMR = 140, 95% CI = 88-211) and multiple myeloma (MM) (SMR = 121, 95% CI = 55-230) were increased, but neither was statistically significant nor likely to be related to refinery employment. No death from asbestosis was reported, and mortality from mesothelioma and pulmonary fibrosis was lower than expected. Lung cancer mortality for the overall cohort was similar to expected. For the overall cohort, analyses by duration of employment and time since first employment showed no evidence of any trends for increasing cause-specific mortality. Separate analyses of male workers employed in operator jobs showed mortality patterns that were more favorable than those of the total cohort. Maintenance craftworkers showed statistically significant elevations in mortality for prostate cancer (SMR = 145, 95% CI = 107-194), leukemia (SMR = 179, 95% CI = 111-273), and other lymphatic tissue cancer (SMR = 233, 95% CI = 138-368). Detailed analyses indicated that, among maintenance craftworkers, mortality was elevated for AML, NHL, and MM, but none was significant. Furthermore, no upward trend by duration of maintenance jobs was observed. A small increase of lung cancer was observed among maintenance craftworkers (SMR = 120, 95% CI = 99-145), which was borderline significant. No relationship between lung cancer and duration of maintenance employment was found. In contrast, a deficit of pulmonary fibrosis was reported among maintenance craftworkers (SMR = 62, 95% CI = 17-159). These findings are discussed in conjunction with results from other refinery studies, and the limitations of the study are discussed.

Multiple myeloma and benzene exposure in a multinational cohort of more than 250,000 petroleum workers.

Case reports have suggested an association between benzene exposure and multiple myeloma. Because petroleum workers are exposed to benzene or benzene-containing liquids, studies of these workers provide an opportunity for investigating the relationship between benzene and multiple myeloma. A large number of cohort studies of petroleum workers have been conducted. However, few of them have reported results of multiple myeloma separately. One reason is that multiple myeloma is usually grouped with other lymphopoietic cancers in the analysis. Another reason is that multiple myeloma is relatively rare, and few individual studies are large enough to provide reliable risk estimates. To determine the risk of multiple myeloma in petroleum (refinery, distribution, production, and pipeline) workers, we have identified 22 cohort mortality studies of petroleum workers in the United States, the United Kingdom, Canada, and Australia. Authors of these studies were contacted, and data on the number of observed deaths and age-specific person-years of observation were requested. Data from individual studies were combined in a pooled analysis (meta-analysis). In addition to the pooled analyses, results for individual cohorts, most of which have never been reported before, are also presented. The combined multinational cohort consisted of more than 250,000 petroleum workers, and the observation period covered an interval of 55 years from 1937 to 1991. A total of 205 deaths from multiple myeloma were observed, compared to 220.93 expected, a total derived from respective national mortality rates. The corresponding standardized mortality ratio (SMR) was 0.93 and the 95% confidence interval (95% CI) was 0.81-1.07. Additional analyses were performed by type of facility and industrial process. Stratum-specific SMRs (95% CIs) were 0.92 (0.77-1.09) for refinery workers and 0.93 (0.69-1.23) for distribution workers. When individual cohorts were stratified by length of observation, no pattern was detected. The pooled analysis indicates that petroleum workers are not at an increased risk of multiple myeloma as a result of their exposure to benzene, benzene-containing liquids, or other petroleum products in their work environment. This conclusion is supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of multiple myeloma and occupational exposures.

Application of meta-analysis in reviewing occupational cohort studies.

Meta-analysis has been used increasingly in reviewing and summarising epidemiological studies. Reviews incorporating meta-analyses have appeared in medical journals in increasing numbers. Although there are several methodology papers on meta-analysis, most of these papers have been written primarily for discussion among epidemiologists. The present paper considers some of the basic methodological issues, the more practical aspects of meta-analysis, and targets an audience of mainly non-epidemiologists. Thus, the main objective of this paper is to provide some basic guidelines for non-epidemiologists to evaluate meta-analysis in occupational cohort studies. In this methodology paper, the limitations and problems of traditional qualitative reviews are pointed out. Some of these problems can be dealt with by quantitative meta-analysis. The potential limitations and benefits of quantitative meta-analysis are discussed. Rather than replacing traditional qualitative review, quantitative meta-analysis should be made part of the overall assessment. The term "meta-review" is proposed to emphasise the importance of both qualitative and quantitative components in a comprehensive review process. The basic steps in a meta-review are outlined, with a discussion on how to recognise and avoid some of the problems which are likely to occur at each step. A meta-review is useful in selecting studies, and in organising, presenting, and summarising results from individual studies. A meta-review can also be used to detect heterogeneity among studies. Major benefits of conducting a meta-analysis (the quantitative component in a meta-review) include the increase in statistical power and the estimate of a properly weighted summary risk estimate.