Workplace airborne hexavalent chromium concentrations for the Painesville, Ohio, chromate production plant (1943-1971).

Hexavalent chromium [Cr(VI)] is recognized as an inhalation carcinogen, based primarily on the increased incidence of lung cancer among occupationally exposed workers. To assess the carcinogenic potency of Cr(VI), both the U.S. Environmental Protection Agency and the Occupational Safety and Health Administration have relied on data from a 1930s cohort of workers from the Painesville, Ohio, chromate production plant. However, the exposure information for this cohort has several shortcomings. In an effort to provide better exposure information, we present here recently identified historical exposure data for the Painesville workers. More than 800 measurements of airborne Cr(VI) from 23 newly identified surveys conducted from 1943 to 1971 are presented. The results indicate that the highest Cr(VI) concentrations recorded at the plant occurred in shipping (e.g., bagging of dichromate), lime and ash, and filtering operations, with maximum yearly average Cr(VI) concentrations of 8.9, 2.7, and 2.3 mg/m(3), respectively. The locker rooms, laboratory, maintenance shop, and outdoor raw liquor storage areas had the lowest average Cr(VI) air concentrations over time, with yearly average concentrations that rarely exceeded the historical and current Threshold Limit Value TLV(R) of 0.05 mgCr(VI)/m(3) (0.1 mgCrO(3)/m(3)). Concentrations generally decreased in the plant over time. The average airborne concentration of Cr(VI) in the indoor operating areas of the plant in the 1940s was 0.72 mg/m(3), that from 1957 through 1964 was 0.27 mg/m(3), and that from 1965 through 1972 was 0.039 mg/m(3). Although in some ways limited, these data are of sufficient quality to allow for exposure reconstruction for workers employed at this plant from 1940 to 1972, and to provide the basis for an improved cancer risk assessment.

Aging adult children with developmental disabilities and their families: challenges for occupational therapists and physical therapists.

The purpose of this article was to review the literature about families of adult children with developmental disabilities, the impact of culture on access to health care services, and community-based health care services for adults with developmental disabilities to answer the following questions: (1) How do parents of adult children with mental retardation and other developmental disabilities describe their caregiving experiences?, (2) What are frequently identified unmet service needs by the parents/families?, (3) Does the family's culture or ethnic background influence how they view their caregiving experiences?, and (4) What are the unique challenges facing families when attempting to access health care services? Currently little information exists about the needs of parents and other family members who live with adults with developmental disabilities. Longitudinal studies and studies to assess the influence of culture on care giving are especially needed. Therapists need to use approaches that will empower children and their families so they can better meet their current challenges and provide a foundation for the skills they will need to meet future challenges as adults.

Assurance: the power behind PCASSO security.

The need for security protection in Internet-based healthcare applications is generally acknowledged. Most healthcare applications that use the Internet have at least implemented some kind of encryption. Most applications also enforce user authentication and access control policies, and many audit user actions. However, most fall short on providing strong assurances that the security mechanisms are behaving as expected and that they cannot be subverted. While no system can claim to be totally "bulletproof," PCASSO provides assurance of correct operation through formal, disciplined design and development methodologies, as well as through functional and penetration testing. Through its security mechanisms, backed by strong system assurances, PCASSO is demonstrating "safe" use of public data networks for health care.

The Clock Drawing Test: utility for dementia detection in multiethnic elders.

BACKGROUND: Disproportionate increases in dementia morbidity in ethnic minorities challenge established screening methodologies because of language and culture barriers, varying access to health services, and a relative paucity of cross-cultural data validating their use. Simple screening techniques adapted to a range of health and social service settings would accelerate dementia detection and social and health services planning for demented minority elders. METHODS: The effectiveness of the Clock Drawing Test (CDT) for dementia detection was compared with that of the Mini-Mental State Examination (MMSE) and the Cognitive Abilities Screening Instrument (CASI) in community-dwelling elders of diverse linguistic, ethnic, and educational backgrounds. Subjects (N = 295) were tested at home in their native languages (English, n = 141; another language, n = 154). An informant-based clinical dementia history and functional severity index derived from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) protocols were used to classify subjects as probably demented (n = 170), and probably not demented (n = 125). RESULTS: All tests were significantly affected by education (p < .001) but not by primary language (p > .05). Sensitivities and specificities for probable dementia were 82% and 92%, respectively, for the CDT; 92% and 92% for the MMSE; and 93% and 97% for the CASI for subjects completing each test. However, in poorly educated non-English speakers, the CDT detected demented subjects with higher sensitivity than the two longer instruments (sensitivity and specificity 85% and 94% for the CDT, 46% and 100% for the MMSE, and 75% and 95% for the CASI). Moreover less information was lost due to noncompletion of the CDT than the MMSE or CASI (severe dementia or refusal: CDT 8%, MMSE 12%, and CASI 16%). CONCLUSIONS: Overall, the CDT may be as effective as the MMSE or CASI as a first-level dementia screen for clinical use in multiethnic, multilingual samples of older adults. Its brevity (1-5 minutes), minimal language requirements, high acceptability, and lack of dependence on specialized testing materials are well adapted for screening of non-English-speaking elderly persons in settings where bilingual interpreters are not readily available and screening time is at a premium.

PCASSO: a secure architecture for access to clinical data via the Internet.

Patient Centered Access to Secure Systems Online (PCASSO) is a National Information Infrastructure research project funded by the US National Library of Medicine (NLM). PCASSO is specifically designed to address the problem of enabling secure access to health information over the Internet, not just for healthcare providers and medical researchers, but also for patients to view their own medical records. The project is using familiar Web technologies to support the search and retrieval of information, including patient demographics, medications, lab tests, and transcription reports. State-of-the-art security technologies protect patient privacy and the integrity of patient information. This paper describes the security architecture of the PCASSO system.

Impact of sample selection on APOE epsilon 4 allele frequency: a comparison of two Alzheimer's disease samples.

OBJECTIVE: In a highly selected sample of unrelated Alzheimer's disease (AD) patients, we found that the APOE epsilon 4 allele frequency was higher than previously reported. Differing selection and ascertainment criteria may lead to these differences. To address this possibility, we compared the epsilon 4 allele frequency in two samples of AD patients selected from the same geographical area. SETTING AND PARTICIPANTS: Cases (n = 55) and controls (n = 99) from a research clinic-based sample were compared with subjects (n = 537) from a community-based AD patient sample. The samples consisted of unrelated cases who met NINCDS/ADRDA criteria for probable AD. DESIGN AND MEASUREMENTS: Clinical characteristics and APOE genotype data were obtained from AD cases and controls from both samples. RESULTS: Frequency of APOE epsilon 4 allele in the research cases compared with the community cases (0.45 vs 0.36) was nearly significant. We compared demographic and clinical characteristics that might account for this difference and found that the research cases were younger, had an earlier age of onset, and had more advanced disease than the community cases. After onset age was controlled, there was no overall difference between epsilon 4 allele frequency of the two samples. CONCLUSIONS: We found that the epsilon 4 allele frequency tended to be higher in the research AD sample compared the community-based sample. The two samples differed in several demographic and clinical characteristics. We conclude that research-based samples may lead to enrollment of younger patients with more severe disease who have higher APOE epsilon 4 allele load. This potential selection bias must be considered in the interpretation of studies of APOE allele frequency.

Ambulatory status of children with cerebral palsy: a retrospective study.

The purpose of this study was to examine the association between (a) nonambulatory status of 19 children with spastic quadriplegia at age 4 years with current ambulatory status and (b) nonambulatory status among these children at age 7 years and ultimate development of independent ambulation, using the physical therapy records. All continued to be nonambulatory at 7 years and are currently. The results suggest (a) a relationship between nonambulatory status at age 4 years and ultimate ambulatory status for children with spastic quadriplegia and (b) remote prospects for the development of independent ambulation in such children who are nonambulatory at age 7 years.

Geographically overlapping Alzheimer's disease registries: comparisons and implications.

In the medical and epidemiologic literature, a registry denotes a data base in which registrants share some common characteristic such as disease category. One criticism of registries is that they frequently collect subjects in a haphazard fashion and, hence, are "nonrepresentative of the population purportedly being represented." In this report, we compare two registries: an incident-based Alzheimer's Disease Patient Registry (ADPR) recruiting subjects for epidemiologic studies from a large health maintenance organization; and an Alzheimer's Disease Research Center (ADRC) registry recruiting subjects for phenomenologic, biologic, and pharmacologic studies. While these registries share personnel, overlap geographically, and use similar diagnostic procedures, they differ substantially in their missions and resulting recruitment strategies. We compared these registries with respect to demographic characteristics and cognitive features at subject entry. Subjects enrolled in the incident-based registry are older and report shorter time between symptom onset and recruitment. They are less demented and mirror the general population demographically more closely than do subjects in the other registry. The ADRC registry contains a much greater proportion of subjects with higher educational attainment.

Improvement in wheelchair propulsion in pediatric wheelchair users through resistance training: a pilot study.

Six children, three with cerebral palsy and three with myelomeningocele, participated in a progressive, 8-week, circuit muscular strength training program. The program was designed to improve wheelchair propulsion, an important functional outcome. Subjects performed three sets of six-repetition maximum (6-RM) upper body strength exercises, three times a week. Exercises included shoulder flexion, extension, abduction, internal and external rotation, elbow flexion, extension, and shoulder flexion/elbow extension (bench press). Subjects exercised quickly with little rest between each set for approximately 30 minutes per session. All children used wheelchairs extensively and participated in a 50-m, and a 12-minute wheelchair propulsion test before and after the 8-week program. The sign test was used to determine if statistically significant (P < or = .05) wheelchair propulsion or 6-RM changes occurred over the training period. Subjects improved significantly (P < or = .031) in all muscular strength (6-RM) measures and the 12-minute distance test. There was a trend toward improvement in the 50-meter test, although this change was not significant (P < or = .05). The results indicate that progressive resistance exercise training seems to improve muscular strength and wheelchair performance in selected disabled children.

Human hepatic triglyceride lipase expression reduces high density lipoprotein and aortic cholesterol in cholesterol-fed transgenic mice.

We have produced a line of transgenic mice expressing human hepatic triglyceride lipase (hH-TGL) to examine the in vivo effects of hepatic lipase expression on high density lipoprotein catabolism. Activation of metallothionine I promoter-hH-TGL cDNA transgene produced high levels of lipase mRNA in liver, heart, and kidney and elevated enzyme activity as assayed in post-heparin plasma. In a series of hyperlipidemic diet studies in which zinc was included in the diet to induce the transgene, hH-TGL expression was associated with a 34% lowering of plasma HDL-cholesterol levels (p < 0.01) when compared with animals on the same hyperlipidemic diet without zinc. This lowering of HDL cholesterol was paralleled by a decrease in total cholesterol and a decrease in HDL particle size. SDS-polyacrylamide gel electrophoresis analysis of the smaller HDL particles revealed that apolipoprotein AI was still the major apoprotein associated with the HDL. Quantitative analysis of abdominal aortic cholesterol content from the same animals suggests that the observed changes in plasma HDL by hH-TGL over-expression correlated with a decrease in the accumulation of aortic cholesterol (42%, p < 0.01). These data support the hypothesis that hH-TGL mediates a non-receptor pathway for the clearance of cholesterol from the plasma compartment.

MDL 29311, an analog of probucol, decreases triglycerides in rats by increasing hepatic clearance of very-low-density lipoprotein.

MDL 29311 is an analog of probucol that shares probucol's antioxidant and antiatherogenic properties. When fed to rats as a 1% dietary admixture, MDL 29311 decreased triglyceride levels by 65% without affecting total or high-density lipoprotein (HDL) cholesterol levels. Under the same conditions, probucol decreased triglyceride levels by 23% and total cholesterol levels by 29% (with a corresponding decrease in HDL cholesterol level). MDL 29311 treatment did not affect the rate of triglyceride entry into the plasma. However, MDL 29311-treated rats cleared in vivo-labeled very-low-density lipoprotein (VLDL)-associated [3H]-triglyceride ([3H]-VLDL) over threefold faster than control rats. This increase in clearance led to increased levels of [3H]-lipid in liver and decreased [3H]-lipid in fat, muscle, diaphragm, and kidney of MDL 29311-treated rats 1.5 to 2.0 minutes after injection of [3H]-VLDL. MDL 29311 treatment had no effect on lipoprotein lipase (LPL) or hepatic triglyceride lipase (H-TGL) activities, or on plasma apolipoprotein (apo) C-II-dependent LPL activation. Intravenously injected [3H]-VLDL was allowed to circulate in MDL 29311-treated or control rats for 1 minute, and the undiluted plasma was then perfused through rat livers in a recirculating system. The [3H] in MDL 29311 plasma was cleared threefold faster (t1/2, 1.3 v 3.8 minutes) than the [3H] in control plasma by control livers. Conversely, the [3H] in control plasma was cleared slowly (t1/2 = 3.5 minutes) by the livers of MDL 29311-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

MDL 29311. Antioxidant with marked lipid- and glucose-lowering activity in diabetic rats and mice.

MDL 29311, an analogue of probucol, administered to rats as a 1% dietary admixture for 2 wk before and 5 days after intravenous injection of 40 mg/kg of ALX significantly (P < 0.05) reduced plasma glucose (6.9 +/- 0.3 vs. 19.2 +/- 1.3 mM) and serum triglyceride (0.17 +/- 0.01 vs. 1.82 +/- 0.39 mM) levels in overnight-fasted ALX-plus-MDL 29311-administered rats vs. ALX-administered rats. A cross-over study indicated that MDL 29311 did not attenuate the diabetogenic action of ALX, but rather, directly lowered glucose and triglycerides. In rats injected intravenously with 45, 65, or 85 mg/kg of STZ and then administered control or MDL 29311 diet for 7 days, MDL 29311 decreased fasted plasma glucose to nondiabetic levels, decreased fasted and nonfasted plasma triglycerides by 49-79%, but did not affect plasma insulin levels. In STZ-induced (65 mg/kg) diabetic rats, MDL 29311 attenuated the increase in plasma nonesterified fatty acids during an 18-h fast; had little or no effect on glucagon, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, or cholesterol; and did not induce hypoglycemia in rats fasted up to 64 h. In nonfasted hyperinsulinemic db/db mice treated for 10 wk, MDL 29311 significantly lowered glucose levels by 14-40%, triglyceride levels by 31-63% and GHb from 8.0 to 5.4%, and had no consistent effect on plasma insulin levels. Because of its marked glucose- and lipid-lowering activity in both nonfasted hyperinsulinemic and fasted insulinopenic animals, MDL 29311 merits additional investigation as a potential antidiabetic agent.

Muscular endurance and wheelchair propulsion in children with cerebral palsy or myelomeningocele.

Bivariate correlations between muscular endurance or resistance used during six-repetition maximum (6-RM) for eight upper body exercises (shoulder flexion, extension, abduction, internal and external rotation, elbow flexion, extension and shoulder flexion/elbow extension (bench press), 50-meter dash, and 12-minute wheelchair propulsion tests were examined in six children with diagnoses of cerebral palsy or myelomeningocele. Correlations were determined before and after resistance training. Before training, only elbow extension correlated significantly with the 12-minute test. Following training, significant correlations (p less than or equal to 0.05) were found between all 6-RM exercises and 12-minute test scores. Additionally, significant correlations were found between all 6-RM exercises (except elbow flexion, which approached significance) and 50-meter dash scores. The results of this clinical case investigation indicate that the relationship between muscular endurance (6-RM) and wheelchair propulsion improves as muscular endurance increases.

Effects of probucol on plasma lipids, lipoproteins and parameters of high density lipoprotein metabolism.

Eight patients with primary hypercholesterolemia were treated with probucol for 17 weeks. Plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol decreased by 16.6, 15.0 and 25.7%, respectively, in response to probucol treatment. Plasma levels of apolipoprotein B and apolipoprotein A-I also decreased, while apolipoprotein A-II concentrations were unchanged. The decrease in HDL-cholesterol levels was associated with a reduction in HDL particle size. No changes in the plasma lecithin:cholesterol acyltransferase activity or mass occurred in response to probucol treatment. In contrast, a significant 25% increase in plasma cholesteryl ester and triglyceride transfer activity occurred following probucol treatment. There was a positive correlation (R = 0.94) between cholesterol ester and triglyceride transfer. We propose that the increase in lipid transfer activity may in part explain the changes in HDL concentration and size, as well as the previously reported effect probucol has on reducing atherosclerosis in animal models.

Trans-repressor activity of nuclear glycosaminoglycans on Fos and Jun/AP-1 oncoprotein-mediated transcription.

Heparin blocks the phorbol ester-induced progression of nontransformed cells through the G0/G1 phase (Wright, T.C., L.A. Pukac, J.J. Castellot, M.J. Karnovsky, R.A. Levine, H.-Y. Kim-Park, and J. Campisi. 1989. Proc. Natl. Acad. Sci. USA. 86: 3199-3203) or G1 to S phase (Reilly, C. F., M. S. Kindy, K. E. Brown, R. D. Rosenberg, and G. E Sonenshein. 1989. J. Biol. Chem. 264:6990-6995) of the cell cycle. Cell cycle arrest was associated with decreased levels of stage-specific mRNAs suggesting transcriptional regulation of cell growth. In the present report, we show that heparin selectively repressed TPA-inducible AP-1-mediated gene expression. Heparin-induced trans-repression was observed in primary vascular smooth muscle cells, as well as in the transformed HeLa cell line and in nondifferentiated F9 teratocarcinoma cells. Inhibition of AP-1-mediated trans-activation occurred with heparin and pentosan polysulfate but not with chondroitin sulfate A or C. Heparin-binding peptides or heparitinase I addition to nuclear lysates of heparin-treated cells allowed enhanced recovery of endogenous AP-1-specific DNA binding activity. We propose a model in which nuclear glycosaminoglycans play a trans-regulatory role in altering the patterns of inducible gene expression.

Gambling in revolutionary Paris - The Palais Royal: 1789-1838.

By the revolution of 1789, the four-story, quadrangular Palais Royal in Paris had become the most glittering tourist center of Europe, with 180 shops and cafes in its ground floor arcades. By 1791, its basement and secondary story contained over 100 separate, illicit gambling operations featuring the most popular dice and card games. The mania for gambling had been transferred from defunct, monarchical Versailles to the thriving, bourgeois Palais Royal, where the five main gaming clubs throbbed from noon till midnight. During the Revolution, Prince Talleyrand won 30,000 francs at one club, and after Waterloo in 1815, Marshal Blucher lost 1,500,000 francs in one night at another. To bring the situation under control and raise taxes for the state, in 1806 Napoleon legalized the main clubs, which from 1819 to 1837 grossed an enormous 137 million francs. When the anti-gambling forces triumphed in 1837 and the clubs were closed down, the National Guard had to be called out to evict the mobs of gamblers who refused to leave the tables. Dramatic reports from Revolutionary police raids, and quotations from the memoirs of humorous French gamblers and shocked foreign visitors, provide anecdotal illustrations of the 49 years during which the Palais Royal was the most intriguing and picturesque gambling mecca of Europe-and probably of the world.