Evaluation of CTPA interpreted as limited in pregnant patients suspected for pulmonary embolism.

PURPOSE: The purpose of this study is to determine the rates of CT pulmonary angiography (CTPA) interpreted as limited and severely limited in pregnant patients suspected for pulmonary embolism (PE), and to evaluate factors that influence these rates. METHODS: This is a retrospective study with CTPA for evaluation of PE in pregnancy across a large health system from 2006 to 2017. CTPA was classified as limited from the radiology report with a subset of those studies classified as severely limited. Bivariate and multivariate analysis was performed for limited and severely limited rates with maternal age and patient size as a continuous variable and race, trimester, patient location study priority status, and result of chest radiograph before CTPA as categorical variables. RESULTS: 874 patients with 33% of studies limited and 4% of studies severely limited. Multivariate logistic regression of CTPA studies revealed decreasing patient age (OR 0.967, p = 0.0129) and increasing patient size (OR 1.013, p < 0.0001). Studies performed in the second trimester (OR 1.869, p = 0.0242) and third trimester (OR 2.314, p = 0.0021) were more likely to be reported as limited (each p < 0.05). Increasing patient size (OR 1.017, p = 0.0046) was the only significant predictor of severely limited versus non-severely limited studies. CONCLUSION: CTPA interpreted as limited in pregnancy are common and may be associated with younger age, larger patient size, and second and third trimesters. However, severely limited interpretations are much less common, with patient size the only significant predictor.

Measures of user experience in a streptococcal pharyngitis and pneumonia clinical decision support tools.

OBJECTIVE: To understand clinician adoption of CDS tools as this may provide important insights for the implementation and dissemination of future CDS tools. MATERIALS AND METHODS: Clinicians (n=168) at a large academic center were randomized into intervention and control arms to assess the impact of strep and pneumonia CDS tools. Intervention arm data were analyzed to examine provider adoption and clinical workflow. Electronic health record data were collected on trigger location, the use of each component and whether an antibiotic, other medication or test was ordered. Frequencies were tabulated and regression analyses were used to determine the association of tool component use and physician orders. RESULTS: The CDS tool was triggered 586 times over the study period. Diagnosis was the most frequent workflow trigger of the CDS tool (57%) as compared to chief complaint (30%) and diagnosis/antibiotic combinations (13%). Conversely, chief complaint was associated with the highest rate (83%) of triggers leading to an initiation of the CDS tool (opening the risk prediction calculator). Similar patterns were noted for initiation of the CDS bundled ordered set and completion of the entire CDS tool pathway. Completion of risk prediction and bundled order set components were associated with lower rates of antibiotic prescribing (OR 0.5; CI 0.2-1.2 and OR 0.5; CI 0.3-0.9, respectively). DISCUSSION: Different CDS trigger points in the clinician user workflow lead to substantial variation in downstream use of the CDS tool components. These variations were important as they were associated with significant differences in antibiotic ordering. CONCLUSIONS: These results highlight the importance of workflow integration and flexibility for CDS success.

User centered clinical decision support tools: adoption across clinician training level.

BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools is a major initiative of the Affordable Care Act's Meaningful Use program. Adoption of CDS tools is multipronged with personal, organizational, and clinical settings factoring into the successful utilization rates. Specifically, the diffusion of innovation theory implies that 'early adopters' are more inclined to use CDS tools and younger physicians tend to be ranked in this category. OBJECTIVE: This study examined the differences in adoption of CDS tools across providers' training level. PARTICIPANTS: From November 2010 to 2011, 168 residents and attendings from an academic medical institution were enrolled into a randomized controlled trial. INTERVENTION: The intervention arm had access to the CDS tool through the electronic health record (EHR) system during strep and pneumonia patient visits. MAIN MEASURES: The EHR system recorded details on how intervention arm interacted with the CDS tool including acceptance of the initial CDS alert, completion of risk-score calculators and the signing of medication order sets. Using the EHR data, the study performed bivariate tests and general estimating equation (GEE) modeling to examine the differences in adoption of the CDS tool across residents and attendings. KEY RESULTS: The completion rates of the CDS calculator and medication order sets were higher amongst first year residents compared to all other training levels. Attendings were the less likely to accept the initial step of the CDS tool (29.3%) or complete the medication order sets (22.4%) that guided their prescription decisions, resulting in attendings ordering more antibiotics (37.1%) during an CDS encounter compared to residents. CONCLUSION: There is variation in adoption of CDS tools across training levels. Attendings tended to accept the tool less but ordered more medications. CDS tools should be tailored to clinicians' training levels.

HIV and HCV health beliefs in an inner-city community.

Chronic infection with the hepatitis C virus (HCV) is more prevalent than human immunodeficiency virus (HIV) infection, but more public health resources are allocated to HIV than to HCV. Given shared risk factors and epidemiology, we compared accuracy of health beliefs about HIV and HCV in an at-risk community. Between 2002 and 2003, we surveyed a random patient sample at a primary care clinic in New York. The survey was organized as domains of Common Sense Model of Self-Regulation: causes ('sharing needles'), timeline/consequences ('remains in body for life', 'causes cancer') and controllability ('I can avoid this illness', 'medications may cure this illness'). We compared differences in accuracy of beliefs about HIV and HCV and used multivariable linear regression to identify factors associated with relative accuracy of beliefs. One hundred and twenty-two subjects completed the survey (response rate 42%). Mean overall health belief accuracy was 12/15 questions (80%) for HIV vs 9/15 (60%) for HCV (P < 0.001). Belief accuracy was significantly different across all domains. Within the causes domain, 60% accurately believed sharing needles a risk factor for HCV compared to 92% for HIV (P < 0.001). Within the timeline/consequences domain, 42% accurately believed HCV results in lifelong infection compared to 89% for HIV (P < 0.001). Within the controllability domain, 25% accurately believed that there is a potential cure for HCV. Multivariable linear regression revealed female gender as significantly associated with greater health belief accuracy for HIV. Thus, study participants had significantly less accurate health beliefs about HCV than about HIV. Targeting inaccuracies might improve public health interventions to foster healthier behaviours and better hepatitis C outcomes.

Improving refugees' reproductive health through literacy in Guinea.

Adult literacy programmes, particularly literacy-for-health programmes that integrate health material in their curricula, are gaining momentum as a means to improve women's and children's health and increase women's empowerment. However, the relationship between literacy skills and these benefits remains unclear. This paper presents results from a study on the Reproductive Health Literacy (RHL) Project among Sierra Leonean and Liberian women in refugee camps in Guinea. Literacy classes met for 2 hours twice per week for 6 months, with content focused on safe motherhood, family planning, STIs/HIV/AIDS and gender-based violence. A closed-ended interview and a written test of literacy skills were administered to 549 former RHL students to understand the programme's effects. Results indicate that participants had a high level of reproductive health knowledge after participation, and reported an increase in literacy skills. Respondents' current use of modern contraception was 48%, of which 23% reported using a condom at last sex. Findings suggest an increase from reported pre-RHL behaviour. Participants also reported a dramatic increase in 'boldness', the phrase used to describe empowerment. While only a third (32%) of respondents considered themselves 'more bold' than other women before RHL, a clear majority (82%) so considered themselves after RHL. A comparison of schooled and unschooled women indicates that those who had had previous schooling did better in RHL than their non-schooled colleagues, but both groups had good knowledge retention, positive behaviour levels and felt more bold after RHL participation.

Changes in HIV/AIDS/STI knowledge, attitudes, and behaviours among the youth in Port Loko, Sierra Leone.

Sierra Leone suffered from 11 years of civil war (1991-2002) resulting in tens of thousands of deaths and mutilations and massive population displacement. In 2001, ARC International, Sierra Leone, conducted a baseline survey of 244 female youth and 293 male youth on knowledge, attitudes, and behaviours around HIV/AIDS and STIs in Port Loko. In 2003, following 2 years of HIV prevention activities, a comparable post-intervention survey of 250 female and 299 male youth was performed. Comparison of baseline and post-intervention results showed that HIV/AIDS knowledge increased dramatically among both groups, with those able to name three effective means of avoiding AIDS increasing from 4% to 36% among female youth, and 4% to 45% among male youth. Reported condom use at last sex increased among female youth from 16% to 46% and among male youth from 16% to 37%. These results demonstrate that, despite the challenges inherent in a post-conflict country, good quality AIDS prevention programmes can be successful.

Evaluation of clinical parameters to predict Mycobacterium tuberculosis in inpatients.

BACKGROUND: Respiratory isolation has been recommended for all patients with suspected tuberculosis (TB) to avoid transmission to other patients and health care personnel. In implementing these guidelines, patients with and without TB are frequently isolated, significantly increasing hospital costs. The objective of this study was to derive a clinical rule to predict the need for respiratory isolation of patients with suspected TB. METHODS: To identify potential predictors of the need for isolation, 56 inpatients with sputum cultures positive for TB were retrospectively compared with 56 controls who were isolated on admission to the hospital based on clinically suspected TB but whose sputum cultures tested negative for TB. Variables analyzed included TB risk factors, clinical symptoms, and findings from physical examination and chest radiography. RESULTS: Multivariate analysis revealed that the following factors were significantly associated with a culture positive for TB: presence of TB risk factors or symptoms (odds ratio [OR], 7.9 [95% confidence interval (CI), 4.4-24.2]), a positive purified protein derivative tuberculin test result (OR, 13.2 [95% CI, 4.4-40.7]), high temperature (OR, 2.8 [95% CI, 1.1-8.3]), and upper-lobe disease on chest radiograph (OR, 14.6 [95% CI, 3.7-57.5]). Shortness of breath (OR, 0.2 [95% CI, 0.12-0.53]) and crackles noted during the physical examination (OR, 0.29 [95% CI, 0.15-0.57]) were negative predictors of TB. A scoring system was developed using these variables. A patient's total score of 1 or higher indicated the need for respiratory isolation, accurately predicting a culture positive for TB (98% sensitivity [95% CI, 95%-100%]; 46% specificity [95% CI, 33%-59%]). CONCLUSION: Among inpatients with suspected active pulmonary TB, a prediction rule based on clinical and chest radiographic findings accurately identified patients requiring respiratory isolation.

Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group.

Clinical experience provides clinicians with an intuitive sense of which findings on history, physical examination, and investigation are critical in making an accurate diagnosis, or an accurate assessment of a patient's fate. A clinical decision rule (CDR) is a clinical tool that quantifies the individual contributions that various components of the history, physical examination, and basic laboratory results make toward the diagnosis, prognosis, or likely response to treatment in a patient. Clinical decision rules attempt to formally test, simplify, and increase the accuracy of clinicians' diagnostic and prognostic assessments. Existing CDRs guide clinicians, establish pretest probability, provide screening tests for common problems, and estimate risk. Three steps are involved in the development and testing of a CDR: creation of the rule, testing or validating the rule, and assessing the impact of the rule on clinical behavior. Clinicians evaluating CDRs for possible clinical use should assess the following components: the method of derivation; the validation of the CDR to ensure that its repeated use leads to the same results; and its predictive power. We consider CDRs that have been validated in a new clinical setting to be level 1 CDRs and most appropriate for implementation. Level 1 CDRs have the potential to inform clinical judgment, to change clinical behavior, and to reduce unnecessary costs, while maintaining quality of care and patient satisfaction. JAMA. 2000;284:79-84

Effect of hemodialysis on the signal-averaged electrocardiogram.

The presence of late potentials (LPs) on signal-averaged electrocardiography (SAECG) is predictive of ventricular tachycardia. The effect of hemodialysis (HD) on SAECG has not been well studied. SAECG was evaluated in 28 patients with chronic renal failure immediately before and after HD. In each SAECG, QRS duration, low-amplitude signal duration (LASd), and root-mean-square voltage of the terminal 40 milliseconds of the QRS (RMS40) were measured. To evaluate the effect of fluid removal on SAECG, the last 12 patients were studied during two different HD sessions, one with and one without fluid removal. Two-dimensional echocardiography was performed before and after HD on these 12 patients. At baseline, four patients met the criteria for LPs on SAECG. Only one patient met the criteria for LPs on SAECG after HD. After HD, the mean LASd decreased (28.3 +/- 12.9 to 24.9 +/- 10.1 milliseconds; P = 0.041) and RMS40 increased (63.0 +/- 56.9 to 79.0 +/- 59.2 microV; P = 0. 006). Among the 12 patients who underwent HD with and without fluid removal, left ventricular end-diastolic dimension decreased with (5. 4 +/- 0.6 to 5.1 +/- 0.6 cm; P = 0.024) but not without fluid removal (5.2 +/- 0.3 to 5.1 +/- 0.4 cm; P = not significant [NS]). RMS40 improved with (43.8 +/- 23.1 to 53.2 +/- 22.6 microV; P = 0. 03) but not without fluid removal (51.0 +/- 26.5 to 51.5 +/- 24.2 microV; P = NS). A significant negative correlation was found between change in body weight and change in RMS40 parameter (r = 0. 456; P = 0.0381). SAECG parameters are abnormal in a significant proportion of patients with chronic renal failure and improve with HD despite electrolyte and other proarrhythmic changes. Decreased left ventricular dimension because of fluid removal during HD is one possible explanation for this improvement.

Health care trends, Part I. The promise and perils of evidence-based medicine ... panel discussion.

Numerous studies have demonstrated that there are wide variations in the way physicians manage similar patients. This suggests that an evidence-based approach could lead to better outcomes with less cost. But practicing evidence-based medicine requires new skills, such as using computerized databases and applying the rules of evidence to primary and integrative studies in the medical literature. The progress of evidence-based medicine will depend in large measure on how quickly these new skills can be developed and integrated into the practice environment. Here's how six experts see the promise and the perils of evidence-based medicine, now and in the new millennium. Part 2 of the panel discussion will explore the new provider team, which includes nurses and, more recently, pharmacists, who are collaborating with physicians to provide disease management and drugs therapy management services.

The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells.

Grape seed proanthocyanidins are natural antioxidants which possess a broad spectrum of chemoprotective properties against free radicals and oxidative stress. In this study, we have assessed the cytotoxicity of a novel IH636 grape seed proanthocyanidin extract (GSPE) against MCF-7 human breast cancer cells, A-427 human lung cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562 chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h using cytomorphology and MTT cytotoxicity assay. In addition, we compared the effects on normal human gastric mucosal cells and normal J774A.1 murine macrophage cells with the effects on the cancer cell lines. Concentration- and time-dependent cytotoxic effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung cancer and gastric adenocarcinoma cells. Following incubation of the MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43% inhibitions in cell growth were observed at 24, 48 and 72 h of incubation, respectively, while incubation of the MCF-7 cells with 50 mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell growth at these same points, respectively. Similar results were observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells. However, GSPE enhanced the growth and viability of the normal human gastric mucosal cells and J774A.1 murine macrophage cells. These data demonstrate that GSPE exhibited cytotoxicity towards some cancer cells, while enhancing the growth and viability of the normal cells which were examined.

Coinfection of macaques with simian immunodeficiency virus and simian T cell leukemia virus type I: effects on virus burdens and disease progression.

To test the hypothesis that coinfection with human immunodeficiency virus (HIV) and human T cell leukemia/lymphoma virus types I or II (HTLV-I or -II) accelerates progression to AIDS, pig-tailed macaques were inoculated with the simian counterparts, SIV and STLV-I. During 2 years of follow-up of singly and dually infected macaques, no differences in SIV burdens, onset of disease, or survival were detected. However, in the first coinfected macaque that died of AIDS (1 year after infection), >50% of CD4+ and CD8+ lymphocytes expressed CD25. On the basis of the low incidence of HTLV-I- and STLV-I-associated disease during natural infections, this early evidence of neoplastic disease was unexpected. While these results demonstrate that coinfection with SIV and STLV-I has no influence on the development of immunodeficiency disease, they do establish a reliable macaque model of persistent STLV-I infection.

Mechanism of gastroprotection by bismuth subsalicylate against chemically induced oxidative stress in cultured human gastric mucosal cells.

Reactive oxygen species (ROS) are implicated in the pathogenesis of chemically induced gastric mucosal injury. We have investigated the effects of ethanol, hydrochloric acid (HCl), and sodium hydroxide (NaOH) on: (1) enhanced production of ROS including superoxide anion and hydroxyl radicals, (2) modulation of intracellular oxidized states by laser scanning confocal microscopy, and (3) DNA fragmentation, indices of oxidative tissue, and DNA damage in a primary culture of normal human gastric mucosal cells (GC), which were isolated and cultured from Helicobacter pylori-negative endoscopic biopsies from human subjects. The induction of ROS and DNA damage in these cells following exposure to ethanol (15%), HCl (150 mM) and NaOH (150 mM) were assessed by cytochrome c reduction (superoxide anion production), HPLC detection for enhanced production of hydroxyl radicals, changes in intracellular oxidized states by laser scanning confocal microscopy, and DNA damage by quantitating DNA fragmentation. Furthermore, the protective ability of bismuth subsalicylate (BSS) was assessed at concentrations of 25, 50, and 100 mg/liter. Incubation of GC with ethanol, HCI, and NaOH increased superoxide anion production by approximately 8.0-, 6.1-and 7.1-fold and increased hydroxyl radical production by 13.3-, 9.6-, and 8.9-fold, respectively, compared to the untreated gastric cells. Incubation of GC with ethanol, HCl, and NaOH increased DNA fragmentation by approximately 6.7-, 4.3-, and 4.8-fold, respectively. Approximately 20.3-, 17.5-, and 13.1-fold increases in fluorescence intensities were observed following incubation of gastric cells with ethanol, HCl, and NaOH, respectively, demonstrating dramatic changes in the intracellular oxidized states of GC following exposure to these necrotizing agents. Preincubation of GC with 25, 50, and 100 mg/liter of BSS decreased ethanol-induced increases in intracellular oxidized states in these cells by 36%, 56%, and 66%, respectively, demonstrating a concentration-dependent protective ability by BSS. Similar results were observed with respect to BSS in terms of superoxide anion and hydroxyl radical production, and DNA damage. The present study demonstrates that ethanol, HCl, and NaOH induce oxidative stress and DNA damage in GC and that BSS can significantly attenuate gastric injury by scavenging these ROS.

Emergency contraception among refugees and the displaced.

In 1994, the international relief community began to recognize and address the reproductive health needs of refugees and displaced populations. A minimum initial service package of reproductive health services for refugees and the displaced, which includes emergency contraception (EC), was developed and recommended for use in refugee settings. This paper describes the experience of one international relief organization, the International Rescue Committee (IRC), in introducing EC into its worldwide reproductive health program. A recent IRC survey found that EC is available in 4 out of 14 settings where it provides reproductive health services. A case study from Tanzania demonstrates the modes of delivery, the demand for EC by women who have experienced sexual violence, and the community responses to this method of contraception. More information, education, and communication directed at refugee communities; more donor support for supplies; and institutional commitment to train staff are needed to expand refugee access to EC.

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Monitoring and evaluation of PMM efforts: what have we learned?

One element of the operations research carried out by the Prevention of Maternal Mortality (PMM) teams in West Africa was a test of the indicators they used to monitor and evaluate their efforts. A small number of process indicators directly related to the PMM interventions in the health facilities and in the communities was selected and monitored. An examination of the teams' experiences in gathering and using these indicators shows: (i) that they are extremely useful for project design and management; (ii) that the necessary data are obtainable; (iii) that staff need training to gather, interpret and use the data; (iv) that monitoring and evaluation systems must be designed so that managers will use the information; and (v) that data on the costs of interventions can be tracked and are useful for evaluation and replication.

A prospective study of the effect of I.V. pentamidine therapy on ventricular arrhythmias and QTc prolongation in HIV-infected patients.

STUDY OBJECTIVES: I.V. pentamidine therapy in HIV-infected patients has been associated in case reports and one uncontrolled prospective series with frequent prolongation of the rate-corrected QT interval (QTc) and a high risk for potentially lethal ventricular arrhythmias, especially torsade de pointes. The aim of this study was to prospectively examine in a controlled manner the effect of I.V. pentamidine therapy on the QT interval and the incidence of ventricular arrhythmias. DESIGN: Open, nonrandomized, prospective evaluation of ventricular arrhythmia incidence in HIV-infected patients receiving pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) utilizing Holter monitoring prior to and during therapy with these agents. SETTING: Staten Island University Hospital, Staten Island, NY. PATIENTS: Twenty-seven HIV-infected patients, of whom 16 received I.V. pentamidine and 11 received I.V. TMP-SMX. MEASUREMENTS AND RESULTS: Study patients underwent Holter monitoring prior to therapy and during the first 3 days and last 2 days of therapy with pentamidine or TMP-SMX, 12-lead ECG prior to and every 24 to 48 h, serum electrolytes prior to and on days 3, 6, 9, and 12 of therapy, and baseline transthoracic two-dimensional and Doppler echocardiography. In the pentamidine group, the results for each monitoring period were as follows (means are presented +/- SEM): pretherapy, 1.66+/-1.03 (median=0) premature ventricular complexes (PVCs) per hour, zero nonsustained ventricular tachycardia (NSVT), zero sustained ventricular tachycardia (VT); early therapy, 1.55+/-0.91 (median=0.04) PVCs per hour, two NSVT (both < or = 5 complexes), zero sustained VT; late therapy, 1.69+/-1.17 (median=0.08) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for early or late therapy as compared to pretherapy for PVCs per hour, NSVT, or sustained VT). In the TMP-SMX group, the Holter monitoring results were as follows: pretherapy, 1.36+/-1.27 (median=0) PVCs per hour, zero NSVT, zero sustained VT; early therapy, 0.71+/-0.53 (median=0.03) PVCs per hour, two NSVT, zero sustained VT; late therapy, 0.56+/-0.51 (median=0) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for pretherapy, early therapy, or late therapy with TMP-SMX as compared to pentamidine for PVCs per hour, NSVT, or VT). The QTc also did not significantly differ during therapy with pentamidine as compared to TMP-SMX. The mean QTc in the pentamidine group decreased during therapy as compared to pretherapy with the difference approaching significance for days 2, 4, and 6 with pentamidine (p<0.06). CONCLUSIONS: QTc prolongation during therapy with pentamidine in HIV-infected patients is not as frequent an occurrence as has been reported previously. In the absence of QTc prolongation, pentamidine therapy was not associated with a significant increase in PVCs, NSVT, or sustained VT as compared to pretherapy recordings or as compared to therapy with TMP-SMX.

Agonist activation of delta-opioid receptor but not mu-opioid receptor potentiates fetal calf serum or tyrosine kinase receptor-mediated cell proliferation in a cell-line-specific manner.

Activation by opioid receptors of cell proliferation was examined with fibroblast cell lines stably expressing either delta-opioid or mu-opioid receptors. Addition of [D-Ala2, D-Leu5]-enkephalin or [D-Pen2,D-Pen5]-enkephalin to Chinese hamster ovary (CHO) cells transfected with delta-opioid receptor cDNA resulted in an agonist concentration-dependent potentiation of fetal calf serum (FCS)-stimulated cell proliferation. This potentiation by delta-opioid agonists was antagonized by naloxone and was not observed with the kappa-opioid receptor selective agonist U50,488 or the mu-opioid receptor selective agonist [D-Ala2,N-MePhe4, Gly-ol5]-enkephalin. This delta-opioid agonist effect was not observed at FCS concentrations > 0.1% and could be blocked by pretreating cells with pertussis toxin, indicating that Gi/Go were involved in this action. In addition, delta-opioid agonists could potentiate CHO cell proliferation stimulated by those growth factors that are mediated by tyrosine kinase receptors (i.e., insulin, insulin-like growth factor 1, and fibroblast-derived growth factor b). This delta-opioid agonist potentiation of growth apparently was dependent on the level of delta-opioid receptors that were expressed and had cell-line selectivity. Activation of delta-opioid receptors expressed in Rat-1 or NIH3T3 fibroblast did not result in a modulation of the cell growth induced by FCS or by growth factors. Interestingly, in CHO cells transfected with mu-opioid receptor cDNA, activation with agonists did not produce a potentiation of FCS-stimulated proliferation. This lack of mu-opioid receptor effect was not due to the differences among CHO clones. In a CHO cell line transfected with both delta-opioid receptor cDNA and mu-opioid receptor cDNA, activation of delta-but not mu-opioid receptors resulted in a potentiation of growth. These data suggest that delta- and mu-opioid receptors in CHO cells activate similar but divergent second messenger pathways, resulting in the differential regulation of cell growth.