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HICNet Medical News Digest Mon, 15 Aug 1994 Volume 07 : Issue 36 Today's Topics: [MMWR 5 Aug 94] Blood Lead Levels [MMWR] Hantavirus Pulmonary Syndrome [MMWR] Vaccination Coverage of 2-Year Old Children Announcements of New Psychology Mailing Lists Forensic Dentistry Conference FDA Statement of the Control and Manipulation of Nicotine in Cigarettes +------------------------------------------------+ ! ! ! Health Info-Com Network ! ! Medical Newsletter ! +------------------------------------------------+ Editor: David Dodell, D.M.D. 10250 North 92nd Street, Suite 210, Scottsdale, Arizona 85258-4599 USA Telephone +1 (602) 860-1121 FAX +1 (602) 451-1165 Internet: mednews@stat.com Bitnet: ATW1H@ASUACAD Mosaic WWW: http://biomed.nus.sg/MEDNEWS/welcome.html Compilation Copyright 1994 by David Dodell, D.M.D. All rights Reserved. License is hereby granted to republish on electronic media for which no fees are charged, so long as the text of this copyright notice and license are attached intact to any and all republished portion or portions. The Health Info-Com Network Newsletter is distributed biweekly. Articles on a medical nature are welcomed. If you have an article, please contact the editor for information on how to submit it. If you are interested in joining the automated distribution system, please contact the editor. Associate Editors: E. Loren Buhle, Jr. Ph.D. Dept. of Radiation Oncology, Univ of Pennsylvania Tom Whalen, M.D., Robert Wood Johnson Medical School at Camden Douglas B. Hanson, Ph.D., Forsyth Dental Center, Boston, MA Lawrence Lee Miller, B.S. Biological Sciences, UCI Dr K C Lun, National University Hospital, Singapore W. Scott Erdley, MS, RN, SUNY@UB School of Nursing Jack E. Cross, B.S Health Care Admin, 882 Medical Trng Grp, USAF Albert Shar, Ph.D. CIO, Associate Prof, Univ of Penn School of Medicine Martin I. Herman, M.D., LeBonheur Children's Medical Center, Memphis TN Stephen Cristol, M.D., Dept of Ophthalmology, Emory Univ, Atlanta, GA Subscription Requests = mednews@stat.com anonymous ftp = vm1.nodak.edu; directory HICNEWS FAX Delivery = Contact Editor for information ---------------------------------------------------------------------- Date: Mon, 15 Aug 94 06:10:16 MST From: mednews (HICNet Medical News) To: hicnews Subject: [MMWR 5 Aug 94] Blood Lead Levels Message-ID: <T4o4qc1w165w@stat.com> Blood Lead Levels -- United States, 1988-1991 Since the late 1970s, ongoing contamination of the U.S. environment by lead has been substantially reduced as major uses of lead in house paint, gasoline, water-distribution systems, and food cans have been eliminated or reduced (1). During the 1980s, blood lead data from both selected populations and convenience samples indicated a continuation of the decline in blood lead levels (BLLs) (2) observed during 1976-1980 during the Second National Health and Nutrition Examination Survey (NHANES II) (3). However, research during the past two decades has demonstrated adverse health effects at BLLs previously considered to be safe (1). This report summarizes estimates of BLLs in the U.S. population from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III), compares these estimates to those from NHANES II, and examines demographic patterns of BLLs among children aged 1-5 years (4,5). NHANES III is a population-based survey of the health and nutritional status of the civilian, noninstitutionalized U.S. population during 1988-1994. Phase 1 data were collected during October 1988-October 1991. Because blacks and Mexican-Americans* were oversampled, reliable prevalence estimates could be obtained for non-Hispanic black and non-Hispanic white persons and for Mexican-Americans but not for other racial/ethnic groups. Household interviews and physical examinations were conducted in a mobile examination center. A 1 mL sample of whole blood was obtained from each participant aged greater than 1 year. Lead content in whole blood was measured by graphite furnace atomic absorption spectrophotometry at CDC. Lead levels below the limit of detection of 1 ug/dL were assigned a level of 0.5 ug/dL. Software for Survey Data Analysis (SUDAAN) was used to calculate estimated means, prevalences, and standard errors that accounted for the sample weights and complex sample design. For the U.S. population, the geometric mean (GM) BLL during 1988-1991 was 2.8 ug/dL (95% confidence interval [CI]=2.7-3.0), a 78% decline in the estimated GM BLL since 1976-1980. The decrease in GM BLL was similar across age groups (Figure 1). As a result, the cross-sectional age trend in GM BLLs remained virtually unchanged: the highest GM BLLs were among persons aged 1-2 years (4.1 ug/dL), and the lowest were among persons aged 12-19 years (1.6 ug/dL). Among persons aged 20-74 years, GM BLL levels increased gradually with age. The prevalence of BLLs greater than or equal to 10 ug/dL among children aged 1-5 years decreased substantially, from 88.2% during NHANES II to 8.9% during NHANES III, Phase 1. The prevalence of elevated BLLs varied by race/ethnicity, income, and residence (Figure 2). For example, an estimated 35% of non-Hispanic black children who were poor (i.e., household income less than 1.3 times the poverty level**) and lived in the central city of a standard metropolitan statistical area had BLLs greater than or equal to 10 ug/dL, compared with 5% of nonpoor, non-Hispanic white children living outside of central cities. The prevalences of BLLs exceeding higher thresholds among children also decreased. In NHANES II, 53% of children aged 1-5 years had BLLs greater than or equal to 15 ug/dL, and 9.3% had BLLs greater than or equal to 25 ug/dL. In NHANES III, the prevalences of children exceeding these same levels decreased to 2.7% (90% CI=1.7%-3.8%) and 0.5% (90% CI=0.1%-0.9%), respectively. Reported by: Div of Health Examination Statistics, National Center for Health Statistics; Div of Environmental Health Laboratory Sciences and Div of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC. Editorial Note: The findings in this report indicate that the reduction in lead exposure documented during the late 1970s (3) continued during the 1980s. Reduction in at least two exposure sources probably contributed most to this decline. First, the amount of lead used in gasoline declined by 99.8% from 1976 to 1990 (6). Second, the percentage of food and soft-drink cans manufactured in the United States that contained lead solder declined from 47% in 1980 to 0.9% in 1990 (7); these two source reductions have been associated with a reduction of lead in the typical U.S. diet (8). In addition, reduction in leaded gasoline probably has resulted in the reduction of the lead content of dust in and around homes. Other factors contributing to reduced lead exposure include the ban on leaded paint for residential use, promulgation of a standard for lead exposure in industry, the ban on lead-containing solder in household plumbing, ongoing screening of children and educational efforts, and lead paint abatement programs in some jurisdictions. In addition, the number of occupied dwellings built before 1940, when lead-based paint was commonly used, decreased from 24.2 million (30.3% of dwellings) in 1980 to 20.8 million (22.2% of dwellings) in 1989 (9,10). The impact of these changes on BLLs, although substantial for selected persons and subpopulations, is unclear for the population as a whole. Because the developing nervous system is particularly sensitive to lead toxicity, reducing lead exposure among infants, toddlers, and preschool children is of particular concern. The findings in this report indicate that, despite a dramatic decline in lead exposure among children, approximately 1.7 million children aged 1-5 years still have BLLs at a level (i.e., greater than or equal to 10 ug/dL) that can affect cognitive development (1). Poor, non-Hispanic black children, who reside disproportionately in center cities, are at increased risk for harmful BLLs. The demographic pattern of elevated BLLs in children probably reflects, in part, the distribution of two remaining reservoirs of lead contamination: 1) deteriorated leaded paint in older housing and 2) urban soil and dust contaminated by past emissions of leaded gasoline and by exterior paint on dwellings and other structures (1). Further reduction in BLLs among children will require reducing exposure to lead from these reservoirs, including programs to safely correct lead hazards in housing and to reduce contact with lead-contaminated soil and dust. In addition, continued enforcement of existing standards to reduce lead exposure from other sources (e.g., drinking water and contaminated dust brought home by lead-exposed workers) should continue. Because elimination of remaining lead exposure sources will take many years, ongoing education of the public is needed about sources of lead exposure and how to avoid them. Finally, young children should be screened according to CDC guidelines to identify those children who develop BLLs high enough to require individualized environmental and medical intervention. References 1. CDC. Preventing lead poisoning in young children: a statement by the Centers for Disease Control. Atlanta: US Department of Health and Human Services, Public Health Service, 1991. 2. Hayes DB, McElvaine MD, Orbach HG, Fernandez AM, Lyne S, Matte TD. Long-term trends in blood lead levels among children in Chicago: relationship to air lead levels. Pediatr 1994;93:195-200. 3. Annest JL, Pirkle JL, Makuc D, Neese JW, Bayse DD, Kovar MG. Chronological trend in blood lead levels between 1976 and 1980. N Engl J Med 1983;308:1373-7. 4. Brody DJ, Pirkle JL, Kramer RA, et al. Blood lead levels in the U.S. population from Phase 1 of the Third National Health and Nutrition Examination Surveys. JAMA 1994;272:277-83. 5. Pirkle JL, Brody DJ, Gunter EW, et al. The decline in blood lead levels in the United States: the National Health and Nutrition Examination Surveys. JAMA 1994;272:284-91. 6. US Environmental Protection Agency. Quarterly summary of lead phasedown reporting data. Washington, DC: US Environmental Protection Agency, Office of Mobile Sources, Office of Air and Radiation, 1991. 7. Can Manufacturers Institute. Food and soft drink can shipments. Washington, DC: Can Manufacturers Institute, 1992. 8. Bolger PM, Carrington CD, Capar SG, Adams MA. Reductions in dietary lead exposure in the United States. Chemical Speciation and Bioavailability 1992;3:31-6. 9. US Department of Commerce/US Department of Housing and Urban Development. Annual housing survey, 1980: part A. General housing characteristics. Washington, DC: US Department of Housing and Urban Development, 1982. (Current housing reports; series H-150-80). 10. US Department of Commerce/US Department of Housing and Urban Development. American housing survey for the United States in 1989. Washington, DC: US Department of Housing and Urban Development, 1991. (Current housing reports; series H-150-89). *Persons residing in survey-sample households who reported their national origin or ancestry as Mexican/Mexican-American. **Poverty statistics are based on definitions originated by the Social Security Administration in 1964, subsequently modified by the federal interagency committees in 1969 and 1980, and prescribed by the Office of Management and Budget as the standard to be used by federal agencies for statistical purposes. ------------------------------ Date: Mon, 15 Aug 94 06:10:59 MST From: mednews (HICNet Medical News) To: hicnews Subject: [MMWR] Hantavirus Pulmonary Syndrome Message-ID: <15o4qc2w165w@stat.com> Hantavirus Pulmonary Syndrome -- Northeastern United States, 1994 On January 20, 1994, a 22-year-old Rhode Island man died of acute respiratory distress approximately 5 hours after hospitalization. This report summarizes the case investigation. The man had sought care at an emergency department in Rhode Island on January 18 complaining of chills and diffuse myalgias and arthralgias. On evaluation in the emergency department, he had a temperature of 100.8 F (38.2 C). His complete blood count (CBC) showed a normal platelet count of 199,000/mm3, a hematocrit of 40.5%, and a white blood cell count of 3600/mm3 with 36% bands. An acute febrile illness with leukopenia was diagnosed, and he was discharged to outpatient follow-up. On January 20, he returned to the emergency department with fever (101.4 F [38.6 C]), increasing shortness of breath, and cyanosis. He was hypotensive and hypoxemic, and bilateral pulmonary infiltrates were present on chest radiograph. His CBC showed thrombocytopenia (61,000/mm3), elevated hematocrit (50.2%), and a white blood cell count of 17,400/mm3 with 41% bands. His clinical condition deteriorated rapidly, and he required mechanical ventilation for respiratory distress. He died later that day. Because a diagnosis was not established and because the death occurred less than 24 hours after admission, the case was reported to the Rhode Island state medical examiner's office. The medical examiner's office forwarded postmortem blood specimens for evaluation for hantavirus infection to CDC. Using an enzyme-linked immunoglobulin M (IgM) capture immunosorbent assay (ELISA), elevated hantavirus IgM titers were found for the Muerto Canyon virus (MCV) (proposed to be renamed Sin Nombre virus). Postmortem tissue samples were positive for hantavirus antigens by immunohistochemistry. An MCV-like viral sequence was amplified from lung, spleen, liver, and heart tissues by reverse transcription and polymerase chain reaction (RT-PCR). A postmortem diagnosis of hantavirus pulmonary syndrome (HPS) was made. An investigation was conducted by state, county, and city health departments in New York and Rhode Island in conjunction with CDC to characterize the illness and identify the site of exposure and the local rodent reservoir for the virus. The patient had not traveled outside the Northeast within the 2 months before his death; he had spent December 1993 and January 1994 in New York and Rhode Island. Epidemiologic and environmental investigations identified multiple possible exposure sites, including two warehouses in Queens, New York; a vacation home on Shelter Island (Long Island); and his family's residence on Long Island. These sites had a history of rodent infestation within the past 6 months but had no evidence of current rodent activity. The patient's apartment in Rhode Island had no history or evidence of rodent infestation. He had spent 2 weeks in December 1993 cleaning portions of one of the warehouses in Queens, which had been unused for more than 10 years. No other persons were involved in this activity. Testing was conducted on serum specimens from 64 persons with exposures similar to that of the patient, including family, co-workers, and factory workers; no additional cases were identified. Rodents were captured at all suspected exposure sites (a total of 19 rodents from all suspected New York sites and 91 from Rhode Island), but none were seropositive for hantavirus. Trapping will be resumed later in 1994. Reported by: B Mojica, MD, K Henning, MD, E Bell, New York City Dept of Health; A Greenberg, MD, R Edstrom, MD, B Smith, Nassau County Dept of Health, Mineola, Long Island; G Birkhead, MD, S Kondracki, D White, PhD, New York State Dept of Health. U Bandy, MD, E Laposata, MD, M Rittmann, W Combs, PhD, B Matyas, MD, State Epidemiologist, Rhode Island Dept of Health. Div of Vector-Borne Infectious Diseases and Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; Div of Field Epidemiology, Epidemiology Program Office, CDC. Editorial Note: As of July 28, 1994, a total of 83 cases of HPS have been identified in the United States; 45 (54%) of these patients have died. Ninety-six percent of these cases have been identified west of the Mississippi River, where Peromyscus maniculatus (deer mouse) is the primary reservoir of MCV (1-3). The range of P. maniculatus includes all of the United States, except the southeast and the Atlantic seaboard. Infected rodents have no signs of infection; however, they shed virus in their saliva, urine, and feces. Humans exposed to infected rodent excreta can develop HPS. The patient in Rhode Island had a history of exposure to a previously closed space with rodent infestation; such exposures have been associated with HPS (1). The small number of rodents caught at suspected exposure sites in New York probably was attributed to excessively cold weather. Four cases of HPS have been identified outside the range of P. maniculatus, one each in eastern Texas, Louisiana, Florida, and Rhode Island. In Florida, a new but related virus (recently named Black Creek Canal virus [BCCV]) isolated from Sigmodon hispidus (cotton rat) is genetically distinct from MCV (4) and from sequences demonstrated by RT-PCR in lung tissues from a person who died of HPS in Louisiana (5). Initial serologic testing at CDC of an acute-phase serum sample from the Florida patient demonstrated the presence of only immunoglobulin G to MCV by direct ELISA, although IgM to MCV was detected by the Western blot assay performed at the University of New Mexico (S. Jenison and B. Hjelle, University of New Mexico, Albuquerque, personal communication, 1994) (6). However, repeat serologic testing at CDC using BCCV antigens showed IgM antibodies. Sequence analysis of the RT-PCR fragment from lung tissue of the patient in this report suggests the presence of a variant of MCV or a new, related virus. Taxonomic assessment of the infecting agent probably will require identification of the reservoir host and additional sequence information from viruses in the northeastern United States. Although the overall incidence of HPS is unknown, the syndrome appears to be widespread geographically. Recognition of HPS during its early stages is difficult because of the nonspecificity of symptoms; later in the syndrome, tachypnea, hemoconcentration, thrombocytopenia, leukocytosis with a high proportion of bands, and other features are suggestive of HPS (7,8). Prompt control of hypoxia (which can rapidly worsen), avoidance of excessive fluid administration, and the early use of ino-tropic and pressor drugs appear particularly important in treating HPS (7,8). CDC has provided intravenous ribavirin for investigational open-label use in treating HPS since June 1993. On July 19 and 20, 1994, eight experts from outside of CDC reviewed the results of the open-label ribavirin protocol. Ribavirin was generally well tolerated in patients with HPS but had no clearly positive influence on outcome. As a result, enrollment under this protocol will close September 1, 1994. No controlled studies of this agent have been conducted in patients with HPS. Clinicians and public health officials should remain alert for persons who have unexplained febrile illness with bilateral interstitial infiltrates, and appropriate specimens should be collected for serologic and tissue diagnostic assays. Suspected cases of HPS should be reported to CDC through state health departments. References 1. CDC. Hantavirus infection--southwestern United States: interim recommendations for risk reduction. MMWR 1993;42(no. RR-11). 2. CDC. Hantavirus pulmonary syndrome--United States, 1993. MMWR 1994;43:45-8. 3. Childs JE, Ksiazek TG, Spiropoulou CF, et al. Serologic and genetic identification of Peromyscus maniculatus as the primary rodent reservoir for a new hantavirus in the Southwestern United States. J Infect Dis 1994;169:1271-80. 4. CDC. Newly identified hantavirus--Florida, 1994. MMWR 1994;43:99,105. 5. CDC. Update: hantavirus disease--United States, 1993. MMWR 1993;42:612-4. 6. Jenison S, Yamada T, Morris C, et al. Characterization of human antibody responses to Four Corners hantavirus infections among patients with hantavirus pulmonary syndrome. J Virol 1994;68:3000- 6. 7. CDC. Update: hantavirus pulmonary syndrome--United States, 1993. MMWR 1993;42:816-20. 8. Duchin JS, Koster FT, Peters CJ, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. New Engl J Med 1994;330:949-55. ------------------------------ Date: Mon, 15 Aug 94 06:11:42 MST From: mednews (HICNet Medical News) To: hicnews Subject: [MMWR] Vaccination Coverage of 2-Year Old Children Message-ID: <86o4qc3w165w@stat.com> Vaccination Coverage of 2-Year-Old Children -- United States, Third Quarter, 1993 In 1993, the Childhood Immunization Initiative (CII) was instituted to increase vaccination coverage among 2-year-old children to at least 90% by 1996 for four of the five vaccines routinely recommended for children* and to at least 70% for three doses of hepatitis B vaccine (1). To monitor progress toward these goals, national estimates of vaccination coverage are needed. This report presents national estimates of vaccination coverage among 2-year-old children derived from provisional data from the National Health Interview Survey (NHIS) for the third quarter of 1993 and describes the trend in vaccination coverage since 1992, the baseline year. The NHIS, a probability sample of the civilian, noninstitutionalized U.S. population, provides quarterly data to calculate these national estimates (2). From July through September 1993, the NHIS collected vaccination data from a random sample (n=483) of survey respondents during household interviews. Vaccination records were available for the children of 33.7% of respondents; for 61.1% of respondents, such records were unavailable and data were based on parental recall. Children's vaccination history was obtained from both sources by 4.4% of respondents and was unknown or refused by 0.8%. For data measurement, 2-year-old children were defined as persons aged 19-35 months at the time of the survey. The children for whom data were collected were a mean age of 27 months, were born during August 1990-February 1992, and had ranged in age from 2 to 15 months (the recommended ages for vaccination) sometime during October 1990-May 1993. Data were weighted to provide national estimates. Confidence intervals were calculated using standard errors generated by the Software for Survey Data Analysis (SUDAAN) (3). Compared with 1992 baseline data from the NHIS, data for the third quarter of 1993 indicate that coverage levels for the individual vaccinations recommended routinely for children and the combined series** of vaccinations increased among 2-year-olds (Table 1) (4). Coverage with three or more doses of vaccine increased for diphtheria and tetanus toxoids and pertussis vaccine (DTP)/DT (from 83.0% to 89.9%), for polio vaccine (from 72.4% to 80.4%), for Haemophilus influenzae type b vaccine (Hib) (from 28.2% to 60.3%), for any measles-containing vaccine (MCV) (from 82.5% to 85.9%), and for the 4:3:1 combined series (from 55.3% to 71.6%). Baseline data for hepatitis B vaccine were not available. The increases are statistically significant (p less than 0.05) for all vaccines (except MCVs) and the 4:3:1 combined series. Reported by: Assessment Br, Data Management Div, National Immunization Program; Div of Health Interview Statistics, National Center for Health Statistics, CDC. Editorial Note: The findings in this report document an increasing trend in the level of vaccination coverage in the United States from 1992 through the third quarter of 1993 and demonstrate continuing progress toward the 1996 vaccination coverage goal of the CII. During this period, vaccination levels for DTP, polio vaccine, and MCVs were the highest ever reported among 2-year-olds in the United States. However, these levels remain below the CII's 1996 goal of at least 90% coverage. Specifically, an estimated 500,000 U.S. children aged 19-35 months lack at least three doses of DTP; 1 million need one or more doses of polio vaccine, and 750,000 need one or more doses of an MCV. Overall, only an estimated 72% of children received the complete 4:3:1 combined series; therefore, an estimated 1.5 million children need one or more doses to be fully vaccinated. The findings in this report are subject to at least one limitation. Because a substantial proportion of the NHIS data was based on parental recall, the data may be subject to recall bias or other reporting errors. Beginning with the 1994 survey, all vaccination histories will be verified by reviewing provider records. Although vaccination levels increased for Hib from 1992 through the third quarter 1993 and for hepatitis B vaccine through the first three quarters of 1993, coverage with these vaccines remained substantially low compared with levels for DTP, polio, and MCV. Two factors may account for the low level of coverage with three doses of Hib. First, most of the NHIS data in this report were for children who were born after promulgation of the recommendations for universal administration of Hib in October 1990 (5). Because nationwide implementation of recommendations does not occur immediately among providers, the anticipated increase in vaccination coverage levels often occurs several months to several years after implementation. Although universal vaccination with Hib has been fully implemented in the United States, the expected increase in Hib coverage levels will be adequately reflected only in future reports. This report documents an increase of 32 percentage points in Hib coverage from 1992 through third quarter 1993. Second, catch-up of children in need of Hib can be accomplished with fewer than three doses. For example, a 15-month-old child who never received a dose of Hib needs only one dose. One factor may account for the low level of hepatitis B coverage. Most of the NHIS data in this report were for children born before the recommendations for universal hepatitis B vaccination were promulgated in November 1991 (6). Consequently, most of these children did not receive this vaccine when they were the recommended ages for vaccination. To compensate for the time required to fully implement universal vaccination, the 1996 CII vaccination coverage goal for hepatitis B vaccine is 70% rather than 90%. The reasons for the overall increase in vaccination coverage levels from 1992 through the third quarter of 1993 are unclear. One possible explanation is associated with the recent measles epidemic in the United States during 1989-1991. During and immediately after the epidemic, a substantial number of the children for whom the NHIS data in this report were provided were the recommended ages for routine vaccination. The immediate risk for measles, the heightened awareness that preschool children needed vaccinations, and the media's focus on the severity and complications of vaccine-preventable diseases may have established vaccination as a high priority among parents and providers (7). As a result, parents may have intensified efforts to seek vaccinations for their children and providers may have more consistently sought to vaccinate children at the earliest recommended ages. However, the effects of efforts aimed at increasing vaccination coverage during and/or after an outbreak of vaccine-preventable disease may be temporary. The substantial number of undervaccinated children in the United States and the possibly temporary increases in vaccination coverage after the recent measles resurgence underscore the importance of fully implementing the CII, which focuses on 1) improving delivery, 2) reducing vaccine cost for parents (e.g., Vaccines for Children program), 3) raising public and provider awareness, 4) monitoring coverage and disease, and 5) improving vaccines and their use. Implementation of this initiative will assist in further increasing coverage to meet the 1996 goals and establishing a vaccination-delivery system that can maintain high coverage levels. References 1. CDC. Reported vaccine-preventable diseases--United States, 1993, and the Childhood Immunization Initiative. MMWR 1994;43:57-60. 2. Massey JT, Moore TF, Parsons VL, et al. Design and estimation for the National Health Interview Survey, 1985-94. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, CDC, 1989. (Vital and health statistics; series 2, no. 11). 3. Shah BV. Software for Survey Data Analysis (SUDAAN) version 5.5 [Software documentation]. Research Triangle Park, North Carolina: Research Triangle Institute, 1991. 4. CDC. Vaccination coverage of 2-year-old children--United States, 1992-1993. MMWR 1994; 43:282-3. 5. ACIP. Haemophilus B conjugate vaccines for prevention of Haemophilus influenzae type B disease among infants and children two months of age and older: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-1). 6. ACIP. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination--recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-13). 7. CDC. Public-sector vaccination efforts in response to the resurgence of measles among preschool-aged children--United States, 1989-1991. MMWR 1992;41:522-5. *At least three doses of diphtheria and tetanus toxoids and pertussis vaccine (DTP), polio vaccine, and Haemophilus influenzae type b vaccine (Hib), and one dose of measles-containing vaccine (MCV) (either measles-mumps-rubella, measles-rubella, or measles vaccine). **There are two combined series of vaccinations: the 4:3:1 schedule--four or more doses of DTP/DT, three or more doses of polio vaccine, and one dose of MCV; and the 3:3:1 schedule-- three doses of DTP/DT, three or more doses of polio vaccine, and one dose of MCV. Monthly Immunization Table To track progress toward achieving the goals of the Childhood Immunization Initiative (CII), CDC publishes monthly a tabular summary of the number of cases of all diseases preventable by routine childhood vaccination reported during the previous month and year-to-date (provisional data). In addition, the table compares provisional data with final data for the previous year and highlights the number of reported cases among children aged less than or equal to 5 years, who are the primary focus of CII. Data in the table are derived from CDC's National Notifiable Diseases Surveillance System. ------------------------------ Date: Mon, 15 Aug 94 06:12:32 MST From: mednews (HICNet Medical News) To: hicnews Subject: Announcements of New Psychology Mailing Lists Message-ID: <L8o4qc4w165w@stat.com> The following announcements of a dozen "InterPsych" lists reated to psychiatry and psychology were submitted by Ian Pitchford <I.Pitchford@sheffield.ac.uk> and general questions may be directed to him. Lists included: attachment on mailbase@mailbase.ac.uk psychiatry-resources on mailbase@mailbase.ac.uk psychiatry on mailbase@mailbase.ac.uk depression on mailbase@mailbase.ac.uk clinical-psychology on mailbase@mailbase.ac.uk child-psychiatry on mailbase@mailbase.ac.uk helplessness on mailbase@mailbase.ac.uk traumatic-stress on mailbase@mailbase.ac.uk transcultural-psychology on mailbase@mailbase.ac.uk psychiatry-assessment on mailbase@mailbase.ac.uk psy-language on mailbase@mailbase.ac.uk psycho-pharm on listserv@netcom.com Additional information is provided when you subscribe to one of these lists. mgh ---------------------------------------------------------------------- attachment on mailbase@mailbase.ac.uk This list welcomes discussion on Bowlby-Ainsworth's theory of attachment. From theoretical and philosophical issues, to clinical or applied issues. Particular emphasis is given to socio-affective and defensive processes, and unconscious representations. To join send the message join attachment firstname lastname to mailbase@mailbase.ac.uk Owner: attachment-request@mailbase.ac.uk ---------------------------------------------------------------------- psychiatry-resources on mailbase@mailbase.ac.uk This list is intended for those who wish to co-operate in the compilation of a resource guide to enable clinicians and academics in the areas of psychiatry and abnormal psychology to gain maximum benefit from the facilities available over the Internet. To join send the message join psychiatry-resources firstname lastname to mailbase@mailbase.ac.uk Owner: psychiatry-resources-request@mailbase.ac.uk ---------------------------------------------------------------------- psychiatry on mailbase@mailbase.ac.uk Many research findings and viewpoints in psychiatry are controversial,leaving a gulf between those pursuing radically different approaches to mental illness. This forum will act as a bridge between those taking a biomedical approach and those taking a psychodynamic approach. To join send the message join psychiatry firstname lastname to mailbase@mailbase.ac.uk Owner: psychiatry-request@mailbase.ac.uk ---------------------------------------------------------------------- depression on mailbase@mailbase.ac.uk This forum exists for scholarly discussion of issues related to mood disorders in clinical and research settings. Integrative biological- psychological contributions are particularly welcome. Topics include causation, correlates, consequences, co-morbidity, treatment/prevention, etc. To join send the message join depression firstname lastname to mailbase@mailbase.ac.uk Owner: depression-request@mailbase.ac.uk ---------------------------------------------------------------------- clinical-psychology on mailbase@mailbase.ac.uk This list promotes the exchange of ideas on matters relevant to clinical psychology, and particularly to the practice of clinical psychology. To join send the message join clinical-psychology firstname lastname to mailbase@mailbase.ac.uk Owner: clinical-psychology-request@mailbase.ac.uk ---------------------------------------------------------------------- child-psychiatry on mailbase@mailbase.ac.uk The Child Psychiatry list is devoted to the discussion of various issues around Child and Adolescent Psychiatry. This includes treatment issues, psychopharmacology, inpatient/outpatient care plans, emergency child/adolescent psychiatry etcetera. To join send the message join child-psychiatry firstname lastname to mailbase@mailbase.ac.uk Owner: child-psychiatry-request@mailbase.ac.uk ---------------------------------------------------------------------- helplessness on mailbase@mailbase.ac.uk Learned Helplessness and Explanatory Style was created to discuss the latest research on animals and humans, biological substratum, depression, anxiety, prevention, CAVE, politics, children, personal control, health, battering, bereavement, PTSD, sex differences, pessimism, work, heritability. To join send the message join helplessness firstname lastname to mailbase@mailbase.ac.uk Owner: helplessness-request@mailbase.ac.uk ---------------------------------------------------------------------- traumatic-stress on mailbase@mailbase.ac.uk This list promotes the investigation, assessment, and treatment of the immediate and long-term psychosocial, biophysiological, and existential consequences of highly stressful (traumatic) events. Of special interest are efforts to identify a cure of PTSD (Post-traumatic Stress Disorder) To join send the message join traumatic-stress firstname lastname to mailbase@mailbase.ac.uk Owner: traumatic-stress-request@mailbase.ac.uk ---------------------------------------------------------------------- transcultural-psychology on mailbase@mailbase.ac.uk Discussion of the delivery of mental health services to diverse cultures. Topics may include, cultural differences in views on mental disorders, culture-specific syndromes, collaboration between Western and traditional healers, and cultural variance in symptoms. 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Contributions welcome. http://www.bubl.bath.ac.uk/BUBL/home.html (BUBL) http://mailbase.ac.uk/welcome.html (MAILBASE) ---------------------------------------------------------------------- ------------------------------ Date: Mon, 15 Aug 94 06:13:19 MST From: mednews (HICNet Medical News) To: hicnews Subject: Forensic Dentistry Conference Message-ID: <w9o4qc5w165w@stat.com> FOR IMMEDIATE RELEASE: FORENSIC DENTISTRY will be presented 13-17 March 1995 at the Holiday Inn Crowne Plaza, Rockville, Maryland, USA. SPONSORS: Armed Forces Institute of Pathology and the American Registry of Pathology. The formal continuing medical education program of the AFIP is accepted by the Academy of General Dentistry for Fellowship, Mastership, and membership maintence credit. GENERAL INFO: AFIP Education Div.,NW, Washington, DC 20306-6000 USA; 301/427-5231; FAX 301/427-5001; INTERNET: LOWTHER@email.afip.osd.mil CONTENT: This course is presented by specialist in the fields of forensic dentistry, criminal investigation, and law. This five-day course will consist of lectures, a mock trial, illustrative situations, and student participation in two laboratory exercises involving the identification of human remains by dental means. Topics to be covered include: * AFIP experience with recent forensic missions. * Mass disaster management. * Bite mark evidence and analysis. (including a limited attendance bite mark analysis exercise)** * New developments in forensic procedures. * Recording and use of dental data in human identification and criminal procedures. ** An optional bite mark analysis exercise will be scheduled on Friday, 17 March 1995 from 3:40 pm until 6:00 pm. There will be NO additional fee for this session. The session is limited to early registrants only, prior to 1 February 1995. Enrollment will be limited to the first 50 paid attendees that request participation. COURSE DIRECTOR: Roberet B. Brannon, Col, USAF, DC TUITION: Early tuition is $595. After 1 February 1995 the tuition is $625. Active duty military, DoD civilians, full-time permanant Department of Veterans Affairs employees (not residents or fellows), and commissioned officers of the Public Health Service with authorized approval have an early registraion fee of $195. After 1 February 1995, this fee will be $225. ------------------------------ Date: Mon, 15 Aug 94 06:19:03 MST From: mednews (HICNet Medical News) To: hicnews Subject: FDA Statement of the Control and Manipulation of Nicotine in Cigarettes Message-ID: <giP4qc1w165w@stat.com> STATEMENT BY DAVID A. KESSLER, M.D. COMMISSIONER OF FOOD AND DRUGS on THE CONTROL AND MANIPULATION OF NICOTINE IN CIGARETTES before the SUBCOMMITTEE ON HEALTH AND THE ENVIRONMENT COMMITTEE ON ENERGY AND COMMERCE U.S. HOUSE OF REPRESENTATIVES JUNE 21, 1994 FOR RELEASE ONLY UPON DELIVERY In my last appearance before this subcommittee on March 25, 1994, I raised the question of whether the Food and Drug Administration should regulate nicotine-containing cigarettes as drugs under the Federal Food, Drug, and Cosmetic Act. A product is a drug if its manufacturer intends it to be used to affect the structure or function of the body. Because of the enormous social consequences of such a decision, we have asked Congress for guidance as we try to answer this question. Mr. Chairman, the American public owes a huge debt of gratitude to this subcommittee for its tireless efforts to focus attention on this most important public health matter. Let me begin by summarizing the information that I presented at that hearing. I reviewed the evidence that supports the scientific consensus that nicotine is addictive. I also reviewed the evidence we had at that time on the ability of the tobacco industry to control nicotine levels, including numerous industry patents for technologies to manipulate and control nicotine content. I described activities of the cigarette industry that resemble those of pharmaceutical manufacturers. I presented information that raised the question of whether tobaccos were blended to manipulate and control nicotine levels. And I provided data showing that over the last decade, nicotine levels have not dropped in parallel with tar levels -- in fact, they have risen. Since March 25th we have continued to focus our analysis and investigation on the physiological and pharmacological effects of nicotine and on the degree to which cigarette companies manipulate and control the level of nicotine in their products. The information that I presented about industry control and manipulation of nicotine the last time I testified before you was suggestive. Today I am going to provide you with actual instances of control and manipulation of nicotine by some in the tobacco industry that have been uncovered through painstaking investigational work over the last three months. We have discovered that manipulation of nicotine has been carried out by some even before tobacco seeds were planted in the fields. We have discovered other forms of manipulation that occur later, in the design and manufacture of cigarettes. Today I want to discuss two examples of nicotine manipulation in some detail. First, we have discovered the deliberate genetic manipulation of the nicotine content in a tobacco plant. It is the story of how an American tobacco company spent more than a decade quietly developing a high- nicotine tobacco plant, growing it in Central and South America, and using it in American cigarettes. Second, I will discuss how chemical compounds are added to cigarettes to manipulate nicotine delivery. I. GENETIC MANIPULATION OF NICOTINE CONTENT The project I am going to tell you about led to development of a tobacco plant code-named "Y-1." (Chart 1) It has been an enormous task to piece together the picture of Y-1. Confidentiality agreements have made getting the facts very difficult. The story begins in Portuguese with our discovery of a Brazilian patent for a new variety of a flue-cured tobacco plant. (Chart 2) One sentence of its English translation caught our eye. "The nicotine content of the leaf of this variety is usually higher than approximately 6% by weight...which is significantly higher than any normal variety of tobacco grown commercially." (Chart 3) Prior to our discovery of the patent, an industry executive had told us that "flue-cured tobacco naturally contains 2.5 to 3.5 percent nicotine." (Chart 4) Thus, this new specially bred plant would contain approximately twice the nicotine that naturally occurs in flue-cured tobacco. The holder of the Brazilian Y-1 patent was Brown & Williamson Tobacco Corporation, maker of such cigarettes as Kool, Viceroy, Richland, Barclay, and Raleigh. Let me tell you why this discovery interested us. Industry representatives have repeatedly stated for the public record that they do not manipulate nicotine levels in cigarettes. The plant described in this patent represents a dramatic attempt to manipulate nicotine. Moreover, when we asked company officials whether plants were bred specifically for higher nicotine content, we were told that this was not feasible. We were told that tobacco growers and cigarette manufacturers have an agreement that the nicotine level of new varieties of tobacco grown in the United States can vary only slightly from the levels of standard varieties. Under this agreement, a new high-nicotine tobacco plant that varied more than slightly from the standard variety could not be commercially grown by farmers in the United States. Nevertheless, we learned that interest in developing a high- nicotine tobacco plant dates back to at least the mid-1970's. In 1977, Dr. James F. Chaplin, then of both the USDA and North Carolina State University, stated: "manufacturers have means of reducing tars but most of the methods reduce nicotine and other constituents at the same time. Therefore it may be desirable to develop levels constant or to develop lines higher in nicotine so that when the tar and nicotine are reduced there will still be enough nicotine left to satisfy the smoker." (Chart 5) In fact, Dr. Chaplin had been working on genetically breeding tobacco plants with varying nicotine levels. In a 1977 paper, Dr. Chaplin indicated that tobacco could be bred to increase nicotine levels, specifically by cross breeding commercial varieties of tobacco with Nicotiana rustica. N. rustica is a wild variety, very high in nicotine, but not used commercially in cigarettes because it is considered too harsh. Dr. Chaplin has told us that his specially bred plants were not commercially viable because they did not grow well and literally did not stand up in the field. Furthermore, he was surprised that he could not get the nicotine levels as high as he anticipated. In fact, in his 1977 paper, the highest nicotine level he reported in these specially bred lines was 3.4 percent total nicotine, within the normal range for flue-cured tobacco. At the same time, international efforts focused on controlling and manipulating nicotine by alternative methods. For example, the use of reconstituted tobacco: "... [LTR, a maker of reconstituted tobacco] which homogenises tobacco for various European cigarette houses cannot only reduce the tar in the sheet it sends back to clients; it is able to work into client's scrap and waste new tobacco of the rustica type, rich in nicotine, in order to change the relationship of nicotine and tar in the sheet. It is able to do the same by the alternative method of adding salts of pure nicotine into the slurry that eventually becomes tobacco sheet. This is an operation parallel to, though more exact than, that on which US geneticists are engaged, in seeking to develop types of tobacco that are low on tar but fairly rich in nicotine." Over the next several years Dr. Chaplin continued his efforts to breed a tobacco plant with a higher nicotine level. During that time, an employee of a Brown & Williamson-affiliated company asked Dr. Chaplin for some of his seeds. Some of Dr. Chaplin's original plant varieties were used as a basis for Brown & Williamson's work. From what we can gather, there was no formal release of this high-nicotine tobacco variety for private use. In the early 1980's, Brown & Williamson grew a number of different plant lines on its experimental farm in Wilson, North Carolina, selecting those that had the best agronomic characteristics. In 1983, Brown & Williamson contracted with DNA Plant Technology to work on tobacco breeding. Much of the developmental work on Y-1 took place in the laboratories, greenhouses, and fields owned by DNA Plant Technology. After he retired from USDA, in 1986, Brown & Williamson also hired Dr. Chaplin as a consultant to work on Y-1 and other projects. The high-nicotine tobacco variety Y-1 was developed by a combination of conventional and advanced genetic breeding techniques. (Chart 6) These include traditional crosses and back crosses between different plant varieties and more sophisticated state-of-the-art breeding techniques including anther culture, (Chart 7) tissue culture, (Chart 8) hybrid sorting, and protoplast fusion (Chart 9) that resulted in cytoplasmic male sterility. The genetic makeup of Y-1 was verified by using genetic engineering techniques involving Restriction Fragment Length Polymorphism (RFLP). (Chart 10) The value of Y-1 to Brown & Williamson is reflected in the fact that Brown & Williamson had DNA Plant Technology make Y-1 into a male sterile plant. This procedure ensures that when a plant is grown it will not produce seeds that can be appropriated by others. Brown & Williamson characterized its achievement in a patent filing as follows (Chart 11): "By the present invention or discovery, applicants have succeeded in developing a tobacco plant that is agronomically and morphologically suitable for commercial tobacco production, i.e. it closely resembles SC 58, and provides a pleasant taste and aroma when included in smoking tobacco products, yet it is possessed of the N. rustica high-nicotine attribute. So far as we know, this has not been accomplished before..." [emphasis in original] What was accomplished was the development of a tobacco plant with a high-nicotine content -- about 6 percent -- that grew well and could be used commercially. The story of this high-nicotine plant continues in Rio Grande do Sul, Brazil. (Chart 12) DNA Plant Technology and Dr. Chaplin both told us they saw Y-1 growing in Brazil in the 1980's. These farms were under contract to Souza Cruz Overseas, a sister company of Brown & Williamson. We do not yet have all the details of how Y-1 came to be growing in Brazil. Until December 13, 1991, export of tobacco seeds or live tobacco plants was prohibited under Federal law (Chart 13) unless a Tobacco Seed Plant Export Permit (Form TB-37) was granted by the United States Department of Agriculture. Such a permit could be granted only after satisfactory proof was offered that the seeds or plants were to be used solely for experimental purposes and then only in amounts of a half a gram or less. Brown & Williamson and DNA Plant Technology have each informed FDA that they believe the other may have been responsible for the shipment of Y-1 seed outside the U.S. We have asked both companies to furnish copies of any Tobacco Seed Plant Export Permits for Y-1. In reading the Brazilian Y-1 patent, we discovered that two related applications for the Y-1 variety of a tobacco plant were filed in the United States. Brown & Williamson filed a U.S. patent application and a Plant Variety Protection Certificate Application in 1991. The company also deposited samples of seeds from this plant with the National Seed Storage Laboratory in Fort Collins, Colorado. When we attempted to obtain the Plant Variety Protection Certificate Application from the U.S. Department of Agriculture, we learned that the application was withdrawn about 3 months ago, on March 14, 1994. We were told that Brown & Williamson also withdrew all seed samples for this variety from the Seed Storage Laboratory. We learned that the U.S. patent application had been rejected by the patent examiner, but that Brown & Williamson had filed an appeal on February 28, 1994. However, two weeks later, on March 16, 1994, before receiving a response to their appeal, Brown & Williamson expressly abandoned the patent. (Chart 14) On Friday, June 10, 1994, DNA Plant Technology told us that it had been authorized by Brown & Williamson to tell FDA that Y-1 was never commercialized. Mr. Chairman, I wish to submit for the record two invoices filed with the U.S. Customs Service in 1992. The invoices are addressed to Brown & Williamson Tobacco Corporation, Louisville, Kentucky from Souza Cruz Overseas. They refer to "Your Order Project Y-1" and reveal that more than one-half a million pounds of Y-1 tobacco were shipped to Brown & Williamson on September 21, 1992. Four days ago, on Friday June 17, after our questioning of DNA Plant Technology, and following our letter to Brown & Williamson indicating that Brown and Williamson had not been cooperative with our investigation, Brown & Williamson told FDA that, in fact, three and a half to four million pounds of Y-1 tobacco are currently being stored in company warehouses in the United States. More significantly, Brown & Williamson revealed that Y-1 had, in fact, been commercialized. Mr. Chairman, these brands of cigarettes -- Viceroy King Size, Viceroy Lights King Size, Richland King Size, Richland Lights King Size, and Raleigh Lights King Size -- were manufactured and distributed nationally in 1993 with a tobacco blend that contains approximately 10 percent of this genetically- bred high-nicotine tobacco called Y-1. (Chart 15) When we asked company officials why they were originally interested in developing a high-nicotine variety of tobacco, they told FDA that they wanted to be able to reduce tar, while maintaining nicotine levels. II. THE CHEMICAL MANIPULATION OF NICOTINE Let me now move on to the second area. In April, the six major American cigarette companies released a list of 599 ingredients added to tobacco. Nicotine is not one of the additives listed. But Mr. Chairman, a number of chemicals on that list increase the amount of nicotine that is delivered to the smoker. Around the time the list was made public, a great deal of interest was directed toward substances on the list that sounded particularly toxic. Among those frequently mentioned was ammonia. Many people may have wondered why the cigarette industry would add ammonia to tobacco. In fact, there are many uses of ammonia. Our investigations have revealed an important one. Let me refer to a major American tobacco company's 1991 handbook on leaf blending and product development. The handbook describes two ways that ammonia can be used in cigarette manufacture. One way is to interact with sugars in the tobacco. But it is the second way, the effect of ammonia and related compounds on the delivery of nicotine to the smoker, that is most striking. Let me quote from that handbook: "[The ammonia in the cigarette smoke] can liberate free nicotine from the blend, which is associated with increases in impact and 'satisfaction' reported by smokers." (Chart 16) The handbook goes on to describe ammonia as an "impact booster": "Ammonia, when added to a tobacco blend, reacts with the indigenous nicotine salts and liberates free nicotine. As a result of such change, the ratio of extractable nicotine to bound nicotine in the smoke may be altered in favor of extractable nicotine. As we know, extractable nicotine contributes to impact in cigarette smoke and this is how ammonia can act as an impact booster." (Chart 17) This important role that ammonia plays in the liberation of free nicotine is also emphasized in other parts of the handbook. "This means that at the same blend alkaloid content, a cigarette incorporating [ammonia technology] will deliver more flavor compounds, including nicotine into smoke than one without it." (Chart 18) It is important to emphasize here that most of the nicotine in the average American cigarette is in the bound form. By that I mean it is not going to readily make its way to the smoker. Mr. Chairman, I am not going to go into the details of acid-base, and vapor-phase chemistry, or the bioavailability of nicotine in the protonated versus the unprotonated form. Suffice it to say that only a fraction of the nicotine in the tobacco gets inhaled by the smoker. The handbook indicates that this ammonia technology enables more nicotine to be delivered to the smoker than if the ammonia technology is not employed. What are the ammonia compounds used in this technology? The company handbook lists a number of different chemical compounds that can act as "impact boosters." Ammonia compounds known to be used include diammonium phosphate (DAP), ammonium hydroxide, and urea. In those countries, such as Germany, that do not allow DAP, other proprietary formulations are used. To what are these compounds added? One of the most common places the ammonia and ammonia-like compounds are applied is to reconstituted tobacco. When the cigarette is burned, the reconstituted tobacco serves as a source of ammonia in smoke. The amount of reconstituted tobacco can be as high as 25 percent of the tobacco in the cigarette. And we've seen ammonia compound levels as high as 10 percent in the reconstituted tobacco. Thus, as the company handbook goes on to state, the benefits of the reconstituted tobacco: "come from being an ammonia source, as well as incorporating sugar-ammonia reactions. As a low alkaloid blend component, it also absorbs nicotine from higher alkaloid-containing components. [It thus becomes]...a positive blend contributor rather than merely a filler." The handbook also says that ammonia can be applied directly to the tobacco that goes into cigarettes. How much additional nicotine does this technology impart? It is our understanding, based on smoke analysis described in the company handbook, that an experimental cigarette made of reconstituted tobacco treated with ammonia has almost double the nicotine transfer efficiency of tobacco. How widespread is ammonia use in the industry? The company handbook states that many U.S. tobacco companies use ammonia technologies. Until we have access to similar documents from other companies, we will not know whether other companies use it directly to affect nicotine levels. To determine how well nicotine content is controlled in cigarettes, FDA laboratories compared the content uniformity of drugs in either tablets or capsules to the content uniformity of nicotine in cigarettes. What is striking is how little the nicotine content varies from cigarette to cigarette, suggesting tight and precise control of the amount of nicotine in cigarettes. In fact, as this chart shows, the nicotine content uniformity of the cigarettes tested meets drug content uniformity standards set by the U.S. Pharmacopeia. (Chart 19) Mr. Chairman, I have presented information on the control and manipulation of nicotine because I believe it raises certain important questions -- questions that are even more important in light of the repeated assertions of the cigarette industry that it does not control or manipulate nicotine. Why spend a decade developing through genetic breeding a high-nicotine tobacco and adding that tobacco to cigarettes if you are not interested in controlling and manipulating nicotine? Why focus on the enhanced delivery of free nicotine to the smoker by chemical manipulation if you are not interested in controlling and manipulating nicotine? III. THE GOALS OF CONTROL AND MANIPULATION Why is there such interest in controlling and manipulating nicotine in cigarettes? Senior industry officials are aware that nicotine is the critical ingredient in cigarettes. Some in the industry have identified target levels of nicotine necessary to satisfy smokers' desire for nicotine. And the industry has undertaken research into nicotine's physiologic and pharmacologic effects. Target ranges Let me give you one example of how a company has identified specific levels of nicotine necessary to satisfy smokers and focused on how to achieve those levels. A company document describes consumer preference testing on "impact," which according to the company correlates with nicotine. The document states that impact is a "high priority" attribute of cigarettes and is: "...controllable to relatively fine tolerances by product development/product intervention...(by manipulating nicotine in blend/smoke...)" (Chart 20) This document goes on to describe an elaborate model for establishing the minimum and maximum nicotine levels tolerated by consumers. It states that the model provides "a median ideal point level for mg nicotine in smoke" for the population tested and a range of tolerable nicotine levels around this ideal point. After applying the testing method to a group of European smokers, for example, the document concludes: "It is clear that consumers are less tolerant of decreases than they are of increases in nicotine delivery. By the time nicotine level falls to approximately 0.35mg, 50% of consumers will be saying that the level of impact is so low they would reject the product. To reach the equivalent stage of 50% of consumers rejecting the product as having too high an impact level, a nicotine level of approximately 5.0mg would be required. Again, it is important to note that there is a clear upper as well as lower rejection limit for nicotine in smoke." It is thus clear that at least one major cigarette manufacturer is aware of the need to target nicotine delivery to levels necessary to satisfy smokers. In fact, as one tobacco flavor specialist has written, one of the most important goals of cigarette design is to "ensure high satisfaction from an adequate level of nicotine per puff," and that even cigarettes with reduced levels of nicotine and tar must have this property. Physiologic and pharmacologic effects of nicotine Publicly available information, including recently released documents, reveals much about the industry's knowledge of the drug-like effects of nicotine. I will begin by describing several studies commissioned by the tobacco industry. As I go through them Mr. Chairman and members of the Subcommittee, ask yourselves: Are these the kinds of studies that would be conducted by an industry interested only in the flavor or taste of nicotine? On May 16, 1994, Brown & Williamson made available previously unreleased results of research that had been conducted more than thirty years ago. A review of this research, known as the Project Hippo studies, documents that the industry was interested in the physiologic and pharmacologic effects of nicotine as early as 1961. The first report, known as Project Hippo I, contained an extensive discussion of the effects of nicotine in the body. This included, for example, the effects of nicotine on the central nervous system. Project Hippo II is an interesting study of what was, in the early 1960's, the newly evolving field of tranquilizers. Let me quote from the opening paragraph of the summary of the Final Report on Project Hippo II: "The aim of the whole research "HIPPO" was to understand some of the activities of nicotine - those activities that could explain why cigarette smokers are so fond of their habit. It was also our purpose to compare these effects with those of the new drugs called "tranquilizers", which might supersede tobacco habits in the near future." (Chart 21) The comparison of the drug-like effects of nicotine and tranquilizers was not exactly a well-kept secret. Even in the 1940's you could pick up a magazine and see an advertisement like this. (Chart 22) What seems to be new about the Hippo study was that it represented a serious commitment by a tobacco company to a scientific examination of this pharmacologic property. Another report released with Hippo and conducted in the 1960's is called "The Fate of Nicotine in the Body." It reviews the state of knowledge about the distribution of nicotine in the body and presents the results of studies on nicotine metabolism in a group of smokers. The report states: "The numerous effects of nicotine in the body may, at first, be conveniently measured by various physiological and pharmacological experiments." (Chart 23) Other statements reportedly made in this paper speak directly to the addictive nature of nicotine. The report goes on to describe what happens when a chronic smoker is denied nicotine: "A body left in this unbalanced state craves for renewed drug intake in order to restore the physiological equilibrium. This unconscious desire explains the addiction of the individual to nicotine." (Chart 31) IV. CONCLUSION The information that we have presented today has been the result of painstaking investigation. We now know that a tobacco company commercially developed a tobacco plant with twice the nicotine content of standard tobacco, that several million pounds of this high-nicotine tobacco are currently stored in warehouses, and that this tobacco was put into cigarettes that have been sold nationwide. We now know that several tobacco companies add ammonia compounds to cigarettes, and that one company's documents confirm that one of the intended purposes of this practice is to manipulate nicotine delivery to the smoker. And we now know that some in the industry have identified target ranges of nicotine delivery. These findings lay to rest any notion that there is no manipulation and control of nicotine undertaken in the tobacco industry. It is equally important to lay to rest, once and for all, the industry's assertion that nicotine is not addictive. Up until very recently, the tobacco industry was able to claim that it did not believe that nicotine was addictive. The release of company documents, and the testimony of company scientists before this Subcommittee, has opened a window on what some senior tobacco officials knew about nicotine's physiological and addictive properties, as much as 30 years ago. One important thing that every teenager in this country needs to know before deciding to smoke his or her first cigarette is how one cigarette industry official viewed the business of selling cigarettes: "We are, then, in the business of selling nicotine, an addictive drug . . ." (Chart 32) Thank you.. REFERENCES 1. Kessler, D.A., Statement on Nicotine-Containing Cigarettes. Testimony before House Subcommittee on Health and the Environment. March 25, 1994. 2. 21 U.S.C. 321(g)(1). 3. Republican Federativa do Brasil, Institute Nacionel da Propriedade Industrial, PI 9203690A, "Variendade de fumo geneticanente estavel e planta de fumo", issued to Brown & Williamson Tobacco Corporation, June 4, 1993. 4. Brazilian Patent No. PI 9203690A. U.S. Department of State, Official English translation. 5. Letter of J.W. Johnson, Chief Executive Officer, R.J. Reynolds Tobacco Company; to D.A. Kessler, Commissioner, Food and Drug Administration; R.J. Reynolds Tobacco Company, Winston-Salem, N.C.; February 28, 1994. 6. Chaplin, J.F. Tailoring Tobacco Plants to Meet Future Demands. World Tobacco October 1978;62:145-9. 7. Chaplin, J.F. Breeding for Varying Levels of Nicotine in Tobacco. Proceedings from a Symposium on Recent Advances in the Chemical Composition of Tobacco and Tobacco Smoke," Raleigh, N.C., 1977:328-39. 8. [Unidentified Author]. Evolving Techniques of Making Cigarettes Milder. World Tobacco April 1979:93-101. 9. U.S. patent no. 761,312. "Filing of Utility Patent Application," Figure 1. 10. U.S. patent no. 761,312, "Appellant's Brief on Appeal," at p. 6. 11. 7 U. S. C. 516. (Tobacco Seed and Plant Exportation Act). 12. 7 CFR 34.4(b). 13. DNA Plant Technology did provide a copy of a Phytosanitary Certificate. This document, which certifies that exported plants or seeds conform with phytosanitary regulations of the importing country, was issued to DNA Plant Technology by U.S. Department of Agriculture, Plant Protection and Quarantine, to facilitate importation of 20 grams of tobacco pollen into Brazil. March 20, 1990. 14. U.S. patent no. 761,312, filed September 17, 1991. 15. Plant Variety Protection Certificate Application, PV No. 9100119, filed February 21, 1991, U.S. Department of Agriculture. (referenced in U.S. patent no. 761,312, "Filing of Utility Patent Application," at p. 1 - unable to obtain copy of application from USDA). 16. U.S. patent no. 761,312, "Rejection of Claims," July 10, 1992. 17. U.S. patent no. 761,312, "Appellant's Brief on Appeal," filed February 28, 1994. 18. U.S. patent no. 761,312, "Express Abandonment of Patent Application," filed March 16, 1994. 19. Redacted copies of United States Customs Service Invoices for Brown & Williamson, dated September 21, 1992. 20. For example, ammonia has been used in efforts to de- nicotinize cigarettes (U.S. patent no. 4,215,706) and, in reconstituted tobacco, for its adhesive properties (U.S. patent no. 5,159,942). 21. Reconstituted tobacco can be made (one of several methods) by mixing tobacco stems, dust, and other scraps, adding a liquid solvent to form a "slurry," and then extracting the liquid and pressing the remaining mixture into a flat sheet. Almost all U.S. cigarettes contain some reconstituted tobacco. (Vogues, E. Tobacco Encyclopedia, published by Tobacco Journal International 1984:389-90.) 22. Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Analysis. Report on analysis of packages of cigarettes. April 4, 1994. 23. Hertz, A.N. The flavourist's role in the cigarette design team. World Tobacco March 1985:97-104. 24. Herach, J., Libert, O., Rogg-Effront, C. Final Report on Project Hippo I. Batelle Memorial Institute, Geneva, for the British American Tobacco Co. Ltd., January 1962 (released by Brown & Williamson Tobacco Corp., May 16, 1994). 25. Haselbach, C.H., Libert, O. Final Report on Project Hippo II. Batelle Memorial Institute, Geneva, for the British American Tobacco Co. Ltd., March 1963 (released by Brown & Williamson Tobacco Corp., May 16, 1994). 26. Geissbuhler, H., Haselbach, C. The Fate of Nicotine in the Body. Batelle Memorial Institute, Geneva, for the British American Tobacco Co. Ltd., May 1963 (released by Brown & Williamson Tobacco Corp., May 16, 1994). 27. Gilbert, D.G., Robinson, J.H., Chamberlin C.L., Speilberger, C.D. Effect of smoking on anxiety, heart rate, and lateralization of EEG during a stressful movie. Psychophysiology 1989;26:311-20. 28. Pritchard, W.S. Electroencephalographic effects of cigarette smoking. Psychopharmacology 1991;104:485-90. 29. Pritchard, W.S., Duke, D.W. Modulation of EEG dimensional complexity by smoking. J Psychophysiology 1992;6(1):1-10. 30. Pritchard, W.S., Gilbert, D.G., Duke, D.W. Flexible effects of quantified cigarette-smoke delivery on EEG dimensional complexity. Psychopharmacology 1993;113:95-102. 31. Meeting. Food and Drug Administration officials; William K. Dunn, former researcher for Philip Morris, Inc.; and counsel to Philip Morris, Inc. Law Offices of Hunton & Williams, Richmond, VA: May 10, 1994. 32. R.J. Reynolds Tobacco Company. New cigarette prototypes that heat instead of burn tobacco. Chap.7;1988:457-459. 33. U.S. patent no. 3,356,094 C1:8-10. 34. Sir Charles Ellis, Scientific Advisor to the Board of British-American Tobacco Co., July 1962 (as reported by Hilts, P.J., in the New York Times, June 16, 1994). 35. Sir Charles Ellis, Scientific Advisor to the Board of British-American Tobacco Co., July 1962 ( as reported by Harris, R., for National Public Radio, June 14, 1994). 36. Hutchison, K., Gray, J.A., Massey, H. (chapter authors). Biographical Memoirs of fellows of the Royal Society of London: Chapter on Charles Drummond Ellis. by the Royal Society 1981;Vol.27:199-233. 37. Sir Charles Ellis, Scientific Advisor to the Board of British-American Tobacco Co., July 1962 (as reported by Harris, R., for National Public Radio, June 14, 1994). 38. Excerpt from a British-American Tobacco Company research chronology from June of 1967 (as reported by Hilts, P.J., in the New York Times, June 17, 1994). 39. Excerpt from a May 30, 1993 British-American Tobacco Company internal document entitled "Confidential: A tentative hypothesis on nicotine addiction" (as reported by Hilts, P.J., in the New York Times, June 17, 1994). 40. Excerpt from a July 1963 Brown & Williamson Tobacco Corporation internal document, authored by its General Counsel Addison Yeaman, analyzing whether the company should acknowledge the hazards of cigarettes or remain quiet (as reported by Hilts, P.J., in the New York Times, May 7, 1994). ------------------------------ End of HICNet Medical News Digest V07 Issue #36 *********************************************** --- Editor, HICNet Medical Newsletter Internet: david@stat.com FAX: +1 (602) 451-1165 Bitnet : ATW1H@ASUACAD