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R D Moore

Publications and source records attributed to R D Moore.

At least 19 recordsLinked to original sources

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n&#x2009;=&#x2009;1,196 reported ever use, n&#x2009;=&#x2009;4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p&#x2009;<&#x2009;5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p&#x2009;>&#x2009;0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans

Intrathecally administered N-methyl-D-aspartate increases persistent hindlimb flexion in rat.

Persistent hindlimb flexion was induced in pentobarbital anesthetized rats using a prolonged, electrical stimulus. Intrathecal (i.t.) N-methyl-D-aspartate NMDA) (1 mM, 5 microliters) applied prior to stimulation increased flexion relative to stimulated controls subsequent to stimulation (156%); 3 days later (109%) and after spinalization at 3 days (91%). Pretreatment with MK-801 (3 mg/kg, i.p.) prevented the enhancement of flexion. Withdrawal latencies to a thermal stimulus also were measured. I.t. NMDA plus stimulation reduced mean latency relative to controls only subsequent to stimulation. Latencies were increased by MK-801 post-injection, post-stimulation and at 3 days. The results suggest that the induction of persistent hindlimb flexion depends upon spinal NMDA receptors.

Animals

Nonlinear modeling of alcohol consumption for analysis of beverage type effects and beverage preference effects.

In a previous report (Kimball and Friedman, Am J Epidemiol, 1992;135:1279-86), linear models for relating health outcomes to alcohol consumption were proposed for differentiating between beverage type effects and beverage preference effects. The models were applied to data relating serum high density lipoprotein cholesterol to alcohol consumption. In this report, those models are extended to the nonlinear case and are applied to data from the 1982 Maryland Hypertension Survey relating systolic blood pressure to alcohol consumption.

Adolescent

Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia.

Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb) production in response to the drug. Plasma hydroxyurea clearances were not a useful guide to maximum tolerated doses of the drug. The mean daily single oral dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 to 35 mg/kg). Among 32 patients, last HbF levels were 1.9% to 26.3% (mean, 14.9%) with increases in HbF over initial values of 1.4% to 20.2% (mean, 11.2%). The most significant predictors of last HbF were last plasma hydroxyurea level, initial white blood count and initial HbF concentration. Last HbF was not related to beta globin haplotype or alpha globin gene number. No serious toxicity was encountered. Clinically significant bone marrow depression was avoided, and chromosome abnormalities after 2 years of treatment were no greater than those observed before treatment. The period of observation has been too short to evaluate the risk of carcinogenesis. Patient's red cells developed striking macrocytosis. Median red cell Hb concentrations did not change. Hb concentrations increased, on average 1.2 g/dL, but serum erythropoietin levels increased. Patients' body weights increased, and some returned to work or school, but no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.

Adult

Safety and cost effectiveness of high-osmolality as compared with low-osmolality contrast material in patients undergoing cardiac angiography.

BACKGROUND AND METHODS: Low-osmolality contrast agents produce fewer hemodynamic and electrophysiologic alterations during cardiac angiography, but they are 20 times more expensive than high-osmolality contrast agents. In a randomized, double-blind trial comparing a nonionic low-osmolality contrast agent (Omnipaque 350) with a high-osmolality agent that does not avidly bind calcium (Hypaque 76) in 505 patients undergoing cardiac angiography, we determined the incidence of minor, mild, moderate, and severe adverse reactions, identified risk factors for such reactions, and evaluated the cost effectiveness of various strategies for the use of contrast material. RESULTS: The 253 patients who received a high-osmolality contrast agent were three times more likely to have a moderate adverse reaction (95 percent confidence interval for the relative risk, 1.6 to 5.5) but no more likely to have a severe reaction (95 percent confidence interval, 0.2 to 2.3) than the 252 patients who received a low-osmolality agent. All 10 severe reactions occurred in patients who were older than 60 years or had unstable angina. Patients with these characteristics were also 3.5 times more likely (95 percent confidence interval, 1.8 to 6.8) to have a moderate reaction (44 of 310 patients, or 14 percent) than those without either characteristic (8 of 195 patients, or 4 percent). We estimated that the incremental cost of each moderate reaction avoided would be $1,698 with a strategy that involved giving a low-osmolality contrast agent only to patients who were over 60 years of age or had unstable angina, instead of giving a high-osmolality agent to all patients. The incremental cost per moderate reaction avoided by giving a low-osmolality contrast agent to all patients rather than only to those over 60 or with unstable angina would be $5,842. CONCLUSIONS: The use of contrast agents with low rather than high osmolality during cardiac angiography reduces the risk of moderate, but not of severe, adverse reactions to the agent used. A strategy of reserving low-osmolality contrast agents for use in patients at high risk for adverse reactions would be more cost effective than one requiring their use in all patients.

Age Factors

Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients.

A randomized double-blind clinical trial was done of aztreonam versus aminoglycoside therapy for the empiric treatment of seriously ill nonneutropenic patients suspected of aerobic gram-negative bacterial infection. Each patient was treated for greater than or equal to 72 h with the study drug. Nephrotoxicity, defined by greater than or equal to 50% increase in baseline serum creatinine, occurred in 12 (15%) of 92 patients receiving aminoglycoside therapy and 1 (1%) of 92 patients receiving aztreonam (P less than .004). More severe nephrotoxicity, defined by greater than or equal to 100% increase in baseline serum creatinine, occurred in 6 (6.5%) of 92 patients receiving aminoglycoside therapy and in 1 of 92 receiving aztreonam (P less than .11). Patients with an elevated baseline total bilirubin level were most likely to develop nephrotoxicity. Auditory toxicity occurred in 2 (7%) of 28 evaluatable patients receiving aminoglycoside therapy and in 1 (3%) of 33 receiving aztreonam (P less than .58). One patient, who received aminoglycoside, developed vestibular toxicity. In nonneutropenic patients believed to be at increased risk for renal dysfunction, aztreonam is a less toxic alternative to aminoglycoside therapy for treatment of suspected aerobic gram-negative infection.

Aminoglycosides

Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group.

Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.

AIDS-Related Opportunistic Infections

Evaluation of a model curriculum on substance abuse at The Johns Hopkins University School of Medicine.

Beginning in 1985, The Johns Hopkins University School of Medicine developed a model curriculum on alcohol abuse to enhance the education of medical students in issues related to the abuse of alcohol and other drugs. By 1987, preclinical courses (given in years one and two) reflected the goals of the curriculum; however, integration of the curriculum into the clinical courses (given in years three and four) was only partially successful. This paper reports on nine annual surveys of students (the classes of 1989-1992) that were conducted from 1987 to 1990 to measure the effects of the curriculum, using previously validated instruments to record the students' knowledge, attitudes, beliefs in role responsibility, and confidence in clinical skills. Significant improvements occurred in the students' attitudes, beliefs in role responsibility, and confidence in skills during their preclinical years. These positive changes were stronger, and better sustained during the clinical years, in students who participated in special programs or elective courses focusing on substance abuse; the positive changes were not always sustained in other students. The authors suggest that enhanced experiential sessions, elective programs, and greater emphasis during the clinical years on issues relating to substance abuse are necessary for maintaining the desirable educational outcomes of a substance abuse management curriculum, and that an intensive program against a backdrop of curriculum reform is a useful model.

Baltimore

Nephrotoxicity of high-osmolality versus low-osmolality contrast media: randomized clinical trial.

The comparative frequency of and risk factors for nephrotoxicity with low-osmolality contrast medium (LOM) versus high-osmolality contrast medium (HOM) were investigated. A randomized, double-blind clinical trial was conducted in patients undergoing diagnostic angiocardiography (n = 430) or contrast material-enhanced body computed tomography (CT) (n = 499). Nephrotoxicity was defined as an increase in serum creatinine level that was greater than both 33% and 0.4 mg/dL (40 mumols/L) above the baseline level within 48 hours after the radiologic procedure. The frequency of nephrotoxicity was similar in patients who received LOM versus those who received HOM: 13 of 479 (2.7%) versus 13 of 450 (2.9%), respectively (P = .87), overall; 4.4% versus 4.0% in angiocardiography patients (P = .84); and 1.2% versus 2.0% in body CT patients (P = .35). Factors associated (P less than .05) with increased risk of nephrotoxicity were insulin-dependent diabetes, baseline serum creatinine level greater than 1.5 mg/dL (130 mumols/L), concurrent use of furosemide, and angiocardiographic examination. Patients who have preexisting renal insufficiency may be at higher risk for nephrotoxicity with HOM than with LOM.

Angiocardiography

Incidence and natural history of Mycobacterium avium-complex infections in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group.

To determine the incidence and natural history of Mycobacterium avium-complex infections in persons with advanced human immunodeficiency virus (HIV) infection, we studied a multicenter cohort of 1,020 persons with acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex (ARC) and CD4 cell count < 0.250 x 10(9)/L initially treated with zidovudine between April 1987 and April 1988. M. avium-complex infections developed in 123 (12%) patients during follow-up, with a 2-yr actuarial risk of 19%. Patients with an initial diagnosis of Pneumocystis carinii pneumonia were more likely to develop M. avium-complex infections than patients with an initial diagnosis of another opportunistic disease or of ARC (p = 0.002). Individuals developing M. avium-complex infections had lower baseline CD4 cell counts, hematocrits, lymphocyte counts, and total white blood cell counts than those who did not develop M. avium-complex infection. During follow-up, individuals who developed M. avium-complex infections were more likely to have severe anemia, to experience zidovudine dose reductions, and to die than were patients without M. avium-complex (p < 0.001). By proportional hazards analysis, a baseline CD4 cell count < 0.100 x 10(9)/L, development of severe anemia, P. carinii pneumonia during follow-up, and zidovudine dose interruption were significantly associated with subsequently developing M. avium-complex infection. A proportional hazards analysis of survival showed that M. avium-complex infection, severe anemia, zidovudine dose interruption, occurrence of an opportunistic infection, CD4 cell count < 0.100 x 10(9)/L, baseline AIDS diagnosis, and transfusion independently predicted an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex

Pneumocystis prophylaxis and survival in patients with advanced human immunodeficiency virus infection treated with zidovudine. The Zidovudine Epidemiology Group.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine. METHODS: A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome-related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival. RESULTS: Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim-sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim-sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP. DISCUSSION AND CONCLUSIONS: Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease.

AIDS-Related Opportunistic Infections

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.

AIDS-Related Complex

Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group.

UNLABELLED: OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study. SETTING: -Hospital and private clinics in 12 metropolitan centers. PATIENTS: -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Acquired Immunodeficiency Syndrome

Zidovudine and the natural history of the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: We sought to describe the trends in survival from 1983 to 1989 among persons with the acquired immunodeficiency syndrome (AIDS) and to examine the relative effects on the natural history of AIDS of zidovudine use and demographic and clinical characteristics. This longitudinal, observational, population-based study used data from the Maryland Human Immunodeficiency Virus Information System, a data base that links information from the Maryland AIDS Registry with data on public and private health care claims, vital statistics, and hospital, long-term care, and ambulatory care records. RESULTS: The median survival after diagnosis among persons with AIDS (n = 1028) was 140 days longer for those given their diagnoses between 1987 and 1989 than for those given their diagnoses between 1983 and 1985 (450 vs 310 days). Among the 714 persons in whom AIDS was diagnosed after April 1987 (when zidovudine became available), two-year survival was greater among men than women (P less than 0.03), among persons less than 45 years old than among older persons (P less than 0.001), among non-Hispanic whites than among minorities (P less than 0.001), and among persons whose category of human immunodeficiency virus transmission was homosexual contact than among those with heterosexual, transfusion-related, or less common modes of transmission (P less than 0.02). In all the analyses the groups with the longer survival were more likely to have received zidovudine. The median survival among those who received zidovudine was 770 days, as compared with 190 days among those who never received the drug (P less than 0.001). By proportional-hazards analysis, zidovudine therapy was the factor most strongly associated with improved survival. CONCLUSIONS: For Maryland residents with AIDS there has been an improvement in survival since 1987. Zidovudine therapy and perhaps other aspects of care associated with it have contributed substantially to the improved survival.

Acquired Immunodeficiency Syndrome

Non-Hodgkin's lymphoma in patients with advanced HIV infection treated with zidovudine.

We wished to determine the incidence of human immunodeficiency virus-related high-grade non-Hodgkin's lymphoma (NHL) and identify factors associated with the development of NHL in patients receiving zidovudine. Data are from a 2-year prospective, observational, multisite study of 1030 patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex who received zidovudine. Non-Hodgkin's lymphoma developed in 24 (2.3%) of 1030 patients who received zidovudine during 1463 person-years of follow-up (rate, 1.6 per 100 person-years of therapy). The relative hazard for development of NHL was stable throughout 2 years of therapy, with the risk of developing NHL 0.8% for each additional 6 months of therapy. Factors associated with development of NHL were a prior diagnosis of Kaposi's sarcoma, herpes simplex virus infection, or lower mean neutrophil count. Less strongly associated was a prior diagnosis of oral hairy leukoplakia or homosexual transmission of HIV. By Cox proportional hazards analysis, a prior diagnosis of Kaposi's sarcoma, cytomegalovirus disease, or oral hairy leukoplakia was most strongly associated with development of NHL. Our study demonstrates a relatively high incidence of NHL in patients with advanced human immunodeficiency virus disease who are undergoing antiretroviral therapy and suggests possible risk factors for development of NHL.

AIDS-Related Complex

Alcohol abuse: comparison of two methods for assessing its prevalence and associated morbidity in hospitalized patients.

PURPOSE: To evaluate two methods for assessing the prevalence of alcohol abuse in hospitalized patients based upon scores on standardized alcoholism screening instruments compared with diagnostic discharge data, and to determine the risk for comorbid conditions in patients who abuse alcohol. PATIENTS AND METHODS: Of 2,534 consecutive patients admitted to five adult inpatient services of an academic center, 1,964 were screened for alcohol abuse using the CAGE and the SMAST. Their discharge diagnoses were obtained and analyzed for the presence of alcohol-related diagnoses and other comorbid conditions. RESULTS: A total of 1.4% of patients had a principal alcohol-related diagnosis (ARD), 6% had a secondary but no principal ARD, and 15% screened positive for alcohol abuse but had no ARD. The overall prevalence of alcohol abuse was 22.4%. Patients with a principal ARD had a higher risk for dementia, chronic obstructive pulmonary disease (COPD), pancreatitis, sequelae of liver disease, and illegal drug abuse. Patients with a secondary ARD were at risk for 19 comorbid conditions, including pancreatitis, injury, pneumonia, COPD, and poly-drug abuse. Patients who screened positive for alcohol abuse but had no ARD were significantly more likely to have a diagnosis of hypertension, arrhythmia, breast cancer, or pelvic inflammatory disease. CONCLUSION: Discharge diagnoses alone markedly underestimate the prevalence of alcohol abuse in hospitalized patients. Patients from the three groups are at higher risk for comorbid conditions, and secondary prevention of alcohol abuse can be achieved by routinely screening every patient using recognized alcoholism screening instruments.

Adolescent

Ceftazidime monotherapy for empiric treatment of febrile neutropenic patients: a meta-analysis.

Whether ceftazidime monotherapy is equal in efficacy to combination regimens (Comb) for empiric treatment of febrile neutropenic patients was tested using meta-analysis. Published studies and abstracts of ceftazidime trials were identified, their quality assessed, the efficacy data abstracted and pooled, and effects of patient and study characteristics examined. The pooled odds ratio (OR) of failure of ceftazidime for febrile episodes was 1.27 (95% confidence interval [CI]: 0.79-2.03; n = 1077) and for bacteremic episodes was 0.72 (CI, 0.33-1.58; n = 248; OR less than 1.0 favors ceftazidime). Results were not significantly affected by type of antibiotic in Comb, age, neutropenia (less than 500/mm3), study quality, or combining abstracts. Results indicate that Comb does not offer a significant advantage over ceftazidime. A subgroup of profoundly neutropenic (less than 100/mm3) patients could not be assessed, raising the possibility that in this important subgroup monotherapy and Comb may not be equivalent. Use of ceftazidime empirically may require modification based on microbiologic results and clinical course.

Adolescent

mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.

Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.

Animals