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Biomedical subjects

K A Bradley

Publications and source records attributed to K A Bradley.

At least 19 recordsLinked to original sources
PubMed2001

Identification of the cellular receptor for anthrax toxin.

The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

Amino Acid Sequence↗
PubMed2001

Binge drinking among female Veterans Affairs patients: prevalence and associated risks.

This study evaluated the prevalence and associated risks of binge drinking, defined as having > or = 4 drinks on an occasion in the past year, in a female patient population. Of 1,259 female Veterans Affairs patients surveyed, 780 reported drinking alcohol in the past year, and 305 (24% of respondents, 39% of drinkers) reported binge drinking in the past year; 84 (11% of drinkers) had done so monthly or more often. Age-adjusted logistic regression analyses indicated that women who reported past-year binge drinking monthly or more often reported significantly increased odds of morning drinking (odds ratio [OR] = 40.3), others worrying about their drinking (OR = 38.6), arguments after drinking (OR = 13.5), hepatitis or cirrhosis (OR = 3.1), frequent injuries (OR = 2.6), smoking (OR = 3.7), drug use (OR = 22.2), and multiple sexual partners (OR = 4.6).

Adult↗
PubMed2001

Variations on the CAGE alcohol screening questionnaire: strengths and limitations in VA general medical patients.

BACKGROUND: Several variations on the CAGE alcohol screening questionnaire have been recommended. This report evaluates modifications and additions to the CAGE. METHODS: Alcohol screening questionnaires were evaluated in male VA general medicine patients (n = 227; mean age, 65.8). Mailed questionnaires included two scoring options for the CAGE (standard and last-year time frames), questions about quantity and frequency of drinking, two questions about episodic heavy drinking, and the question "Have you ever had a drinking problem?" Main analyses compared alcohol screening questions, at various cut-points, to a gold standard of hazardous drinking during the past year (> or =14 drinks/week or > or =5 drinks on an occasion) and/or DSM-III-R alcohol abuse or dependence, based on standardized interviews. RESULTS: The CAGE questionnaire with a past-year time frame was much less sensitive (0.57 vs. 0.77) but more specific (0.82 vs. 0.59) than the standard CAGE for detecting hazardous drinking during the past year and/or DSM-III-R alcohol abuse or dependence. An eight-item questionnaire that included the standard CAGE was most sensitive (0.92) but had low specificity (0.50). A single question about the frequency of drinking > or =6 drinks on an occasion, included in the eight-item questionnaire, was both relatively sensitive (0.77) and specific (0.83). CONCLUSION: The CAGE questionnaire with a past-year time frame was an insensitive alcohol-screening test. An eight-item augmented version of the standard CAGE was the most sensitive. A question about the frequency of drinking > or =6 drinks on an occasion performed better than the standard CAGE, which made it the optimal brief screening test for at-risk drinking.

Aged↗
PubMed2001

The relationship between alcohol screening questionnaires and mortality among male veteran outpatients.

OBJECTIVE: This study evaluated whether responses to alcohol screening questionnaires predicted mortality in a Department of Veterans Affairs (VA) primary care population. METHOD: This study involved 5,703 male outpatients (mean age = 64) who were enrolled in General Internal Medicine clinics at three Veterans Affairs (VA) medical centers and returned mailed questionnaires in 1993-94. The two questionnaires included the CAGE and Alcohol Use Disorders Identification Test (AUDIT) alcohol screening tests. Mortality was ascertained using the VA Beneficiary Identification and Record Locator System. Five-year crude and adjusted mortality rates were calculated for patients who screened positive and patients who screened negative on each alcohol screening test. RESULTS: The risk of mortality was increased among drinkers who scored > or = 8 on the full AUDIT (hazard ratio: 1.47; 95% confidence interval [CI]: 1.08-2.00) or the three AUDIT consumption questions (1.58; 1.11-2.27), after adjusting for age, smoking, sociodemographic characteristics and chronic illnesses. The risk of mortality was also increased among drinkers who reported drinking > or = 3 drinks daily (1.69; 1.28-2.22) or prior alcohol treatment (1.66; 1.27-2.17), in "fully adjusted" models. A positive CAGE score (> or = 2) was associated with significantly increased risk of mortality among drinkers in a model adjusted only for age and smoking (1.27; 1.02-1.58). Among nondrinkers, neither a positive CAGE score (> or = 2) nor report of prior alcohol treatment was associated with increased risk of mortality. CONCLUSIONS: VA outpatients who reported drinking during the previous year and who had a positive result on an alcohol screening test experienced higher mortality over the subsequent 5 years than did patients who screened negative.

Aged↗
PubMed2000

A physician survey of the effect of drug sample availability on physicians' behavior.

OBJECTIVE: Pharmaceutical companies often use drug samples as a marketing strategy in the ambulatory care setting. Little is known about how the availability of drug samples affects physicians' prescribing practices. Our goal was to assess: (1) under what circumstances and why physicians dispense drug samples, (2) if drug samples lead physicians to use medications other than their preferred drug choice, and (3) the physician characteristics that are associated with drug sample use. DESIGN: Cross-sectional survey. SETTING: University-based clinics at one academic medical center. PARTICIPANTS: 154 general medicine and family physicians. MEASUREMENTS AND MAIN RESULTS: Physicians' self-reported prescribing patterns for 3 clinical scenarios, including their preferred drug choice, whether they would use a drug sample and subsequently prescribe the sampled medication, and the importance of factors involved in the decision to dispense a drug sample. A total of 131 (85%) of 154 physicians responded. When presented with an insured woman with an uncomplicated lower urinary tract infection, 22 (17%) respondents reported that they would dispense a drug sample; 21 (95%) of 22 sample users stated that they would dispense a drug sample that differed from their preferred drug choice. For an uninsured man with hypertension, 35 (27%) respondents reported that they would dispense a drug sample; 32 (91%) of 35 sample users indicated that they would dispense a drug sample instead of their preferred drug choice. For an uninsured woman with depression, 108 (82%) respondents reported that they would dispense a drug sample; 53 (49%) of 108 sample users indicated that they would dispense a drug sample that differed from their preferred drug choice. Avoiding cost to the patient was the most consistent motivator for dispensing a drug sample for all 3 scenarios. For 2 scenarios, residents were more likely to report using drug samples than attendings (P <.05). When respondents who chose a drug sample for 2 or 3 scenarios were compared to those who never chose to use a drug sample, or chose a drug sample for only one scenario, only younger age was independently associated with drug sample use. CONCLUSION: In self-reports, the availability of drug samples led physicians to dispense and subsequently prescribe drugs that differ from their preferred drug choice. Physicians most often report using drug samples to avoid cost to the patient.

Adult↗
PubMed1998

The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.

OBJECTIVE: To evaluate the 3 alcohol consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) as a brief screening test for heavy drinking and/or active alcohol abuse or dependence. METHODS: Patients from 3 Veterans Affairs general medical clinics were mailed questionnaires. A random, weighted sample of Health History Questionnaire respondents, who had 5 or more drinks over the past year, were eligible for telephone interviews (N = 447). Heavy drinkers were oversampled 2:1. Patients were excluded if they could not be contacted by telephone, were too ill for interviews, or were female (n = 54). Areas under receiver operating characteristic curves (AUROCs) were used to compare mailed alcohol screening questionnaires (AUDIT-C and full AUDIT) with 3 comparison standards based on telephone interviews: (1) past year heavy drinking (>14 drinks/week or > or =5 drinks/ occasion); (2) active alcohol abuse or dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria; and (3) either. RESULTS: Of 393 eligible patients, 243 (62%) completed AUDIT-C and interviews. For detecting heavy drinking, AUDIT-C had a higher AUROC than the full AUDIT (0.891 vs 0.881; P = .03). Although the full AUDIT performed better than AUDIT-C for detecting active alcohol abuse or dependence (0.811 vs 0.786; P<.001), the 2 questionnaires performed similarly for detecting heavy drinking and/or active abuse or dependence (0.880 vs 0.881). CONCLUSIONS: Three questions about alcohol consumption (AUDIT-C) appear to be a practical, valid primary care screening test for heavy drinking and/or active alcohol abuse or dependence.

Aged↗
PubMed1998

Alcohol screening questionnaires in women: a critical review.

OBJECTIVE: To describe the performance of alcohol screening questionnaires in female patients. DATA SOURCES: We searched MEDLINE from 1966 to July 1997 for alcoholism or alcohol-drinking and for CAGE, AUDIT, BMAST, TWEAK, T-ACE, MAST, SMAST, or SAAST; Citations Indexes for newer screening questionnaires and those without acronyms; and MEDLINE from 1996 to July 1997 for alcoholism or alcohol-drinking and screening. STUDY SELECTION AND DATA EXTRACTION: Reviewed studies presented data for women comparing brief alcohol screening questionnaires with valid criterion standards for heavy drinking (> or =2 drinks per day) or alcohol abuse or dependence in US general clinical populations. Sensitivities, specificities, and areas under receiver operating characteristic curves (AUROCs) were extracted. DATA SYNTHESIS: Thirteen articles (9 studies) were reviewed. The CAGE questionnaire had AUROCs of 0.84 to 0.92 for alcohol abuse and dependence in predominantly black populations of women, but using the traditional cut point of 2 or more resulted in low sensitivities (38%-50%) in predominantly white female populations. The TWEAK and Alcohol Use Disorders Identification Test (AUDIT) questionnaires had high AUROCs (0.87-0.93) for past-year alcohol abuse or dependence in black or white women, but had sensitivities less than 80% at traditional cut points. For detecting heavy drinking, the AUDIT questionnaire had AUROCs of at least 0.87 in female primary care patients. The TWEAK and T-ACE questionnaires had higher AUROCs (0.84-0.87) than the CAGE questionnaire (0.76-0.78) for detecting heavy drinking before pregnancy was recognized in black obstetric patients. CONCLUSIONS: The CAGE questionnaire was relatively insensitive in predominantly white female populations. The TWEAK and AUDIT questionnaires have performed adequately in black or white women, using lower cut points than usual.

Adult↗
PubMed1998

Medical risks for women who drink alcohol.

OBJECTIVE: To summarize for clinicians recent epidemiologic evidence regarding medical risks of alcohol use for women. METHODS: MEDLINE and PsychINFO, 1990 through 1996, were searched using key words "women" or "woman," and "alcohol." MEDLINE was also searched for other specific topics and authors from 1980 through 1996. Data were extracted and reviewed regarding levels of alcohol consumption associated with mortality, cardiovascular disease, alcohol-related liver disease, injury, osteoporosis, neurologic symptoms, psychiatric comorbidity, fetal alcohol syndrome, spontaneous abortion, infertility, menstrual symptoms, breast cancer, and gynecologic malignancies. Gender-specific data from cohort studies of general population or large clinical samples are primarily reviewed. MAIN RESULTS: Women develop many alcohol-related medical problems at lower levels of consumption than men, probably reflecting women's lower total body water, gender differences in alcohol metabolism, and effects of alcohol on postmenopausal estrogen levels. Mortality and breast cancer are increased in women who report drinking more than two drinks daily. Higher levels of alcohol consumption by women are associated with increased menstrual symptoms, hypertension, and stroke. Women who drink heavily also appear to have increased infertility and spontaneous abortion. Adverse fetal effects occur after variable amounts of alcohol consumption, making any alcohol use during pregnancy potentially harmful. CONCLUSIONS: In general, advising nonpregnant women who drink alcohol to have fewer than two drinks daily is strongly supported by the epidemiologic literature, although specific recommendations for a particular woman should depend on her medical history and risk factors.

Alcohol Drinking↗
PubMed1998

The AUDIT alcohol consumption questions: reliability, validity, and responsiveness to change in older male primary care patients.

OBJECTIVES: To determine the reliability, validity, and responsiveness to change of AUDIT (Alcohol Use Disorders Identification Test) questions 1 to 3 about alcohol consumption in a primary care setting. PATIENTS: Randomly selected, male general medical patients (n = 441) from three VA Medical Centers, who had 5 or more drinks containing alcohol in the past year and were willing to be interviewed about their health habits. MEASURES: Three self-administered AUDIT consumption questions were compared with a telephone-administered version of the trilevel World Health Organization interview about alcohol consumption. RESULTS: Of 393 eligible patients, 264 (67%) completed interviews. Test-retest reliability--Correlations between baseline and repeat measures 3 months later for four dimensions of consumption according to the AUDIT, ranged from 0.65 to 0.85, among patients who indicated they had not changed their drinking (Kendall's Tau-b). Criterion validity--Correlations between AUDIT and interview for four dimensions of alcohol consumption ranged from 0.47 to 0.66 (Kendall's Tau-b). Discriminative validity--The AUDIT questions were specific (90 to 93%), but only moderately sensitive (54 to 79%), for corresponding criteria for heavy drinking. Responsiveness to change--The AUDIT consumption questions had a Guyatt responsiveness statistic of 1.04 for detecting a change of 7 drinks/week, suggesting excellent responsiveness to change. CONCLUSIONS: AUDIT questions 1 to 3 demonstrate moderate to good validity, but excellent reliability and responsiveness to change. Although they often underestimate heavy alcohol consumption according to interview, they performed adequately to be used as a proxy measure of consumption in a clinical trial of heavy drinkers in this population.

Adult↗
PubMed1998

Screening for problem drinking: comparison of CAGE and AUDIT. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.

OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled. MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients. The AUDIT was subsequently mailed to "drinkers." Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (> 14 drinks per week typically or > or = 5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population.

Adult↗
PubMed1997

Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate.

In Escherichia coli, the siderophore molecule enterobactin is synthesized in response to iron deprivation by formation of an amide bond between 2,3-dihydroxybenzoate (2,3-DHB) and l-serine and formation of ester linkages between three such N-acylated serine residues. We show that EntB, previously described as the isochorismate lyase required for production of 2,3-DHB, is a bifunctional protein that also serves as an aryl carrier protein (ArCP) with a role in enterobactin assembly. EntB is phosphopantetheinylated near the C terminus in a reaction catalyzed by EntD with a kcat of 5 min-1 and a Km for apo-EntB of 6.5 microM. This holo-EntB is then acylated with 2,3-DHB in a reaction catalyzed by EntE, previously described as the 2,3-DHB-AMP ligase, with a kcat of 100 min-1 and a Km of <<1 microM for holo-EntB. The N-terminal 187 amino acids of EntB (isochorismate lyase domain) are not needed for reaction of EntB with either EntD or EntE as demonstrated by the equivalent catalytic efficiencies of the full-length EntB (residues 1-285) and the C-terminal EntB ArCP domain (residues 188-285) as substrates for both EntD and EntE.

Acylation↗
PubMed1995

Primary and secondary prevention of alcohol problems: U.S. internist attitudes and practices.

OBJECTIVE: To describe internists' involvement in primary and secondary prevention of alcohol-related problems, and to evaluate relationships between preventive practices and training, attitudes, and work patterns. DESIGN: Cross-sectional survey. PARTICIPANTS: A random sample of 152 board-certified internists, < or = 65 years old, who practiced primary care in the continental United States, was selected from the American Medical Association's master list. Ten were ineligible; 99 (70%) of the remaining 142 internists completed questionnaires. MAIN OUTCOME MEASURES: The authors evaluated the internists' preventive practices, including the frequency with which they assessed patients' alcohol consumption and advised patients about safe levels of alcohol consumption. The authors also evaluated the internists' opinions about safe levels of alcohol consumption, training and attitudes regarding advising patients about safe levels of consumption, and work patterns. RESULTS: Ninety-four percent of the respondents believed they had a responsibility to advise all patients about safe levels of alcohol consumption (primary prevention), though only 30% often/always did so. Eighty percent often/always advised patients who drank three or more drinks daily about safe levels of alcohol consumption (secondary prevention), but many (45%) did not routinely ask patients how much they drank daily. Preventive practices correlated positively with the number of hours/week internists practiced primary care, and with their belief in the effectiveness of preventive advice about alcohol consumption. CONCLUSIONS: Internists believe they have a responsibility for primary prevention of alcohol-related problems, but only a minority actively practice it. In contrast, many internists practice secondary prevention, offering advice about safe alcohol consumption to patients who drink three or more drinks daily. The effectiveness of such secondary prevention is limited, however, by incomplete screening regarding level of alcohol consumption.

Adult↗
PubMed1993

How much is too much? Advising patients about safe levels of alcohol consumption.

United States physicians are increasingly encouraged to advise patients about health-related behaviors, such as smoking, but there is minimal discussion in the US medical literature about the need to advise patients about safe levels of alcohol consumption. Several factors likely contribute to this lack of focus on safe drinking practices. These include the complex relationship between drinking and health, limitations in the available epidemiologic data, misinterpretation of the disease model of alcoholism, and physician attitudes. Nevertheless, epidemiologic evidence clearly relates increasing levels of alcohol consumption to increased morbidity and mortality, and research has shown that physician advice can reduce both alcohol consumption and alcohol-related problems. We propose that physicians thoroughly assess patients' alcohol consumption and advise patients who drink about safe levels of consumption.

Alcohol Drinking↗
PubMed1992

Screening and diagnosis of alcoholism in the primary care setting.

As many as 20% of patients seeing their primary physicians may suffer from alcohol abuse and dependence. Often the problem goes unrecognized. In this article I summarize what is known regarding the natural history, risk factors, and available screening techniques for alcoholism. Ultimately, a diagnosis of alcoholism is based on a patient's history, and there are various approaches to obtaining a thorough alcohol history and overcoming patient denial regarding an alcohol problem. Primary physicians have an important role in educating patients about alcoholism.

Alcoholism↗
PubMed1992

Management of alcoholism in the primary care setting.

Primary care physicians can play an important role in managing alcoholic patients. Identifying and treating alcoholism early, before it has interfered with patients' relationships and work, may increase the likelihood of prolonged recovery. Simple office interventions can help motivate patients to abstain and seek treatment. People who abuse alcohol and are unwilling to abstain can benefit from a recommendation to reduce their intake of alcohol. For alcohol-dependent patients who decide to stop drinking, primary care physicians often can manage withdrawal on an outpatient basis. Selecting an appropriate treatment program for each alcoholic patient is important, and referral to a specialist to assist in matching patients to treatments is often necessary. Primary care physicians also can help prevent relapse. Although disulfiram is of limited value, primary care physicians can support recovery by identifying coexistent psychosocial problems, helping patients to restructure their lives, and ensuring continuity of care.

Alcohol Drinking↗