Faculty Bibliography

Cardiovascular disease (CVD) is the leading cause of mortality and a major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD deaths. Currently estimation of risk in primary prevention is based on the Framingham risk equations, which inputs traditional risk factors and is helpful in predicting the development of CHD in asymptomatic individuals. However many individuals suffer events in the absence of established risk factors for atherosclerosis and broad based population risk estimations may have little precision when applied to a given individual. To meet the challenge of CHD risk assessment, several tools have been developed to identify atherosclerotic disease in its preclinical stages. This paper aims to incorporate information from coronary artery calcification (CAC) scoring from a computed tomographic "heartscan" (using Electron Beam Tomography (EBT) as the validated prototype) along with current Framingham risk profiling in order to refine risk on an absolute scale by combining imaging and clinical data to affect a more comprehensive calculation of absolute risk in a given individual. For CAC scores above the 75th percentile but <90th percentile, 10 years is added to chronological age, and for CAC scores above the 90th percentile, 20 years is added to current chronological age. Among those in whom a positive CAC score is the norm such as older individuals (men> or =55 years, women> or =65 years) a CAC = 0 will result in an age point score corresponding to the age-group whose median CAC score is zero i.e., 40-44 years for men and 55-59 years for women. The utilization of CAC scores allows the inclusion of sub-clinical disease definition into the context of modifiable risk factors as well as identifies high-risk individuals requiring aggressive treatment.

Multidrug-resistant tuberculosis (MDR-TB) poses a serious threat to global public health. The mutations responsible for drug resistance in Mycobacterium tuberculosis have been identified, but what impact these mutations have on bacterial fitness is controversial. We analyzed 3 MDR strains of M. tuberculosis obtained from human immunodeficiency virus-negative patients with chronic pulmonary TB. One of these strains harbored a chromosomal deletion encompassing 15 open reading frames. Genes deleted in this strain included acr1, which encodes the virulence factor alpha-crystallin (Acr) 1, a protein that has been reported to be essential for M. tuberculosis replication in macrophages. We found that all 3 MDR isolates, including the acr1-deficient strain, replicated in cultured murine and human macrophages with the same kinetics as H37Rv, a virulent laboratory strain. These observations challenge the prevailing view that MDR bacteria are less fit than drug-susceptible bacteria and indicate that Acr1 is dispensable for bacterial growth in the human lung

OBJECTIVE: To describe MRSA infection and colonization in household pets, and transmission of MRSA between animals and humans. METHODS: MRSA infection and colonization in household pets and human contacts were evaluated during investigations initiated after identification of MRSA infection or colonization of a household pet in order to determine if there had been transmission between animals and humans. All MRSA isolates were screened for Panton-Valentine leukocidin (PVL) genes by use of polymerase chain reaction, and isolate relatedness was determined by use of pulsed-field gel electrophoresis (PFGE). RESULTS: Investigations of six situations where MRSA was identified in one or more animals in a household or veterinary facility were performed. MRSA was isolated from 8 animals (5 dogs and 3 cats) with clinical infections, 1 cat that was in contact with 2 infected cats and 14/88 (16%) of household contacts or veterinary personnel. Both animal-to-human and human-to-animal transmission were suspected. An indistinguishable MRSA isolate was recovered from at least one human that was in contact with each animal case. All isolates were classified as Canadian epidemic MRSA-2, the predominant community-associated MRSA clone in humans in Canada. No isolates possessed genes encoding for the PVL. CONCLUSIONS: Transmission of MRSA between humans and animals, in both directions, was suspected. MRSA appears to be an emerging veterinary and zoonotic pathogen

Blood pressure in women increases after menopause, and sympathetic tone in female rats decreases with estrogen injections in the rostral ventrolateral medulla (RVLM) region that contains bulbospinal C1 adrenergic neurons and is involved in blood pressure control. We investigated the anatomical and physiological basis for estrogen effects in the RVLM. Neurons with alpha- or beta-subtypes of estrogen receptor (ER) immunoreactivity (-ir) overlapped in distribution with tyrosine hydroxylase (TH)-containing C1 neurons. Immunoelectron microscopy revealed that ERalpha- and ERbeta-ir had distinct cellular and subcellular distributions. ERalpha-ir was most commonly in TH-lacking profiles, many of which were axons and peptide-containing afferents that contacted TH-containing dendrites. ERalpha-ir was also in some TH-containing dendrites. ERbeta-ir was most frequently in TH-containing somata and dendrites, particularly on endoplasmic reticula, mitochondria, and plasma membranes. In whole-cell patch clamp recordings from isolated bulbospinal RVLM neurons, 17beta-estradiol dose-dependently reduced voltage-gated Ca(++) currents, especially the long-lasting (L-type) component. This inhibition was reversed by washing or prevented by adding the non-subtype-selective ER antagonist ICI182780. An ERbeta-selective agonist, but not an ERalpha-selective agonist, reproduced the Ca(++) current inhibition. The data indicate that estrogens can modulate the function of RVLM C1 bulbospinal neurons either directly, through extranuclear ERbeta, or indirectly through extranuclear ERalpha in selected afferents. Moreover, Ca(++) current inhibition may underlie the decrease in sympathetic tone evoked by local 17beta-estradiol application. These findings provide a structural and functional basis for the effects of estrogens on blood pressure control and suggest a mechanism for the modulation of cardiovascular function by estrogen in women.

Sopranos [Television Program] -- CHRISTOPHER Moltisanti's (Michael Imperioli) new girlfriend is Julianna (Julianna Margulies), formerly involved with Tony Soprano. Christopher and Julianna meet at an Alcoholics Anonymous meeting, which they attend because of drug addiction. During one of their trysts, Julianna is suffering from a bad cold, and Christopher suggests Robitussin with dextromethorphan. Julianna declines, seeming to know that dextromethorphan is a semi- synthetic narcotic that, if taken in high doses, could make her high and perhaps again provoke her drug addiction. Instead, she suggests eight to 10 tea bags for a container of valerian tea, which she says is in the same chemical family as Valium. She hopes it will help her sleep and treat her cough. When we next see Julianna, her cough is clearly improved, but she is again snorting drugs with Christopher, who carries a container of what appears to be valerian tea

The General Assembly has adopted a strongly worded declaration aimed at pressing the countries of the world to strengthen their battle against AIDS, a global pandemic that Secretary General Kofi Annan called 'the greatest challenge of our generation.' The new document is a political blueprint, not a plan of action. It calls for strong commitments to bolster the rights of women and girls so they can protect themselves from infection with HIV, the virus that causes AIDS. The document also acknowledges the role of men in spreading the disease and their responsibility to respect women. The Center for Health and Gender Equity, which says it represents nearly 70 international advocacy groups, denounced the document for failing to show greater political leadership; refusing to commit to more definitive targets on financing, prevention, care and treatment; and evading frank acknowledgment that some of today's fastest-growing epidemics are occurring among intravenous drug users, prostitutes and gay men

The language of the document surprised even anti-AIDS groups, which said that while it did not satisfy all their objectives, they had feared it would be watered down. In turn, United Nations officials credited the advocacy groups for strengthening the draft in behind-the-scenes struggles during an extraordinary three-day plenary session. The new document is a political blueprint, not a plan of action. It calls for a strong commitments to bolster the rights of women and girls so they can protect themselves from infection with H.I.V., the virus that causes AIDS. The document also acknowledges the role of men in spreading the disease and their responsibility to respect women. [Laura Bush], center, with her daughter Barbara, right, and the American envoy, John R. Bolton, left, at yesterday's General Assembly session. Mrs. Bush gave a generally positive assessment of the AIDS campaign. (Photo by Spencer Platt/Getty Images)

[Kofi Annan] and Dr. Peter Piot, executive director of the AIDS program, spoke as the General Assembly began a three-day meeting aimed at renewing the political commitment urged in 2001 and setting new goals for expenditures and for measuring progress in the battle against AIDS. The General Assembly also heard from Khensani Mavasa of South Africa, who became the first person known to be infected with HIV to address a plenary session about AIDS. Mavasa urged that the new declaration not be 'a document of empty promises,' but 'a platform for targets based on action.' Mavasa said that she had been raped and abused, and recommended setting a goal of ending violence against women. Describing her life as one 'under the power of men and the institutions they run,' she called for making condoms available to everyone and creating a culture that encourages their regular use

Mr. [Kofi Annan] and Dr. Peter Piot, executive director of the AIDS program, spoke as the General Assembly began a three-day meeting aimed at renewing the political commitment urged in 2001 and setting new goals for expenditures and for measuring progress in the battle against AIDS. The General Assembly also heard from Khensani Mavasa of South Africa, who became the first person known to be infected with H.I.V. to address a plenary session about AIDS. Such sessions are normally reserved for United Nations officials and delegates from member countries. Khensani Mavasa of South Africa, addressing the United Nations yesterday, called for making condoms available to all to fight AIDS. (Photo by Stuart Ramson/Associated Press)