Media richness and social information processing: rationale for multifocal continuing medical education activities.

Academic business communication has studied the results of media selection in organizations. Little of this work has been discussed in the context of continuing medical education (CME); however, it may apply to improving the design of educational activities. This article reviews literature on media richness and social information processing theories. The concept of media richness suggests that media choice results from a match between the objective characteristics of the medium and the content requirements of a message. In this context, media include face-to-face conversation and print and electronic media. Social information processing theory suggests that media selection is also based on participants' social norms for how information is communicated in their environment and the participants' familiarity with specific media types. Appraisal of CME with respect to these theories suggests that the complex relationship of CME content and CME participant environments invites the most effective strategies of multiple media experienced over time in what might be called multifocal continuing medical education.

Cutaneous injection of human subjects with macrophage inflammatory protein-1 alpha induces significant recruitment of neutrophils and monocytes.

Macrophage inflammatory protein (MIP-1 alpha), a member of the CC chemokine subfamily, has been shown to attract T cells and monocytes in vitro and to be expressed at sites of inflammation. Although the in vitro activities of MIP-1 alpha have been well documented, the in vivo biological activities of MIP-1 alpha in humans have not been studied. To address this, we challenged human subjects by intradermal injection with up to 1000 pmol of MIP-1 alpha and performed biopsies 2, 10, and 24 h later. Although no acute cutaneous or systemic reactions were noted, endothelial cell activation, as indicated by the expression of E-selectin, was observed. In agreement with its in vitro activity, monocyte, lymphocyte, and, to a lesser degree, eosinophil infiltration was observed, peaking at 10-24 h. Surprisingly, in contrast to its reported lack of in vitro neutrophil-stimulating activity, a rapid infiltration of neutrophils was observed in vivo. This neutrophil infiltration occurred as early as 2 h, preceding the appearance of other cells, and peaked at 10 h. Interestingly, we found that neutrophils in whole blood, but not after isolation, expressed CCR1 on their cell surface. This CCR1 was thought to be functional as assessed by neutrophil CD11b up-regulation following whole-blood MIP-1 alpha stimulation. These studies substantiate the biological effects of MIP-1 alpha on monocytes and lymphocytes and uncover the previously unrecognized activity of MIP-1 alpha to induce neutrophil infiltration and endothelial cell activation, underscoring the need to evaluate chemokines in vivo in humans.

Diffusion of laparoscopic cholecystectomy in the Veterans Affairs health care system, 1991-1995.

CONTEXT: Laparoscopic cholecystectomy has become the most widely used treatment for gallbladder disease. In HMO, Medicare, and fee-for-service settings, cholecystectomy rates increased 28% to 59% after introduction of laparoscopic cholecystectomy. OBJECTIVE: To investigate the impact of the introduction of laparoscopic cholecystectomy on cholecystectomy rates and the operative mortality rate in Veterans Affairs (VA) hospitals. DESIGN: Sequential cross-sectional study. PATIENTS: All patients who underwent cholecystectomy from 1991 (before introduction of laparoscopic cholecystectomy) to 1995. SETTING: 133 VA hospitals. OUTCOME MEASURES: Cholecystectomy rates, use of laparoscopic or open cholecystectomy, and operative mortality rate. RESULTS: The annual number of cholecystectomies in the VA system increased by 10% from 1991 to 1995; the laparoscopic procedure accounted for 25% of the caseload in 1992 and 52% in 1995. Compared with patients having laparoscopic cholecystectomy, those having open cholecystectomy were more likely to be older, be male, and have acute cholecystitis or comorbid illnesses (P < 0.001). The operative mortality rate of open cholecystectomy increased by 46% during this 4-year period (from 2.4% to 3.4%) and was constant for laparoscopic cholecystectomy (about 0.5%). Given the increasing use of the laparoscopic procedure, however, the overall mortality rate of cholecystectomy during surgery decreased by 22% (from 2.4% to 1.8%). Despite increased use of the surgery, the absolute number of deaths decreased by 9%. CONCLUSIONS: The introduction of laparoscopic cholecystectomy in the VA system was not accompanied by a large increase in cholecystectomy rates, as it was in fee-for-service, Medicare, and HMO systems. Because the rate of operations has changed only slightly, the total number of cholecystectomy-related deaths has decreased.

Antagonizing leukotriene B4 receptors delays cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection is a cellular immunological/inflammatory response that is, in part, directed by potent proinflammatory mediators. This study was designed to test the hypothesis that leukotriene B4 (LTB4) may have a role in graft rejection and that LTB4 receptor antagonists may be clinically useful in the treatment of allograft rejection. METHODS: We evaluated the potent and selective LTB4 receptor antagonist CP-105696 in a murine heterotopic cardiac allograft model with oral dosing daily for 28 days or in an induction protocol (day -1 to day 3). RESULTS: At a dose of 50 mg/kg/day (28 days), B10.BR (H2k) allografts transplanted into C57Bl/6 (H2b) recipients were significantly protected, as reflected by the mean survival time versus control grafts (27+/-20 days [n=10] vs. 12+/-6 days [n=14]; P=0.0146). Using an induction protocol (day -1 to day 3), CP-105696 at 100 mg/kg/day significantly prolonged allograft survival (33+/-23 days [n=9]; P=0.0026), but CP-105696 at 10 mg/kg/day did not (18+/-16 days [n=8]; P=0.1433). Syngeneic grafts survived indefinitely (n=11). Immunohistological evaluation of allografts at rejection revealed a mononuclear cell infiltrate composed primarily of CD3+ and CD11b+ (Mac-1+) cells, which were infrequent in syngeneic grafts. Allografts from mice treated with CP-105696 at 50 or 100 mg/kg/day demonstrated a selective reduction in beta2-integrin (Mac-1) expression on monocytes/macrophages, as demonstrated by CD11b staining density compared with allograft controls. CONCLUSIONS: The results suggest that LTB4 or other potential ligands for LTB4 receptors may be important mediators of allograft rejection and support the clinical evaluation of LTB4 receptor antagonists in human organ transplantation.

Predictors of resource utilization for hospitalized patients with Pneumocystis carinii pneumonia (PCP): a summary of effects from the multi-city study of quality of PCP care.

To determine whether patient and hospital characteristics were significantly associated with variations in Pneumocystis carinii (PCP) care and outcomes, we analyzed the use of diagnostic tests, intensive care units (ICUs), anti-PCP medications for persons hospitalized with human immunodeficiency virus (HIV)-related PCP, and hospital discharge status. We conducted retrospective chart reviews of a cohort of 2,174 patients with PCP hospitalized in 1987-1990. Outcomes included process of care for PCP and in-hospital mortality rates. Persons with PCP who were more severely ill at admission were more likely to have early medical care, to receive care in an intensive care unit, and to die in hospital. After we adjusted for differences in this severity of illness, we noted that Medicaid patients, injection drug users (IDUs), and patients treated at VA or county hospitals were significantly less likely than others to have diagnostic bronchoscopies and that persons covered by Medicaid, with a previous diagnosis of acquired immunodeficiency syndrome (AIDS), who did not receive prior zidovudine (AZT) or who received care in a VA hospital had the highest chances of in-hospital death. Insurance and risk group characteristics, severity of illness, and hospital characteristics appear to be the most important determinants of the intensity and timing of medical care and outcomes among patients hospitalized with PCP.

Relationship between procedures and health insurance for critically ill patients with Pneumocystis carinii pneumonia.

The objective of the present study was to assess the association between type of health insurance coverage and use of diagnostic tests and therapies among patients with AIDS-related Pneumocystis carinii pneumonia (PCP). Fifty-six private, public, and community hospitals in Chicago, Los Angeles, and Miami were selected for the study, and the charts of 890 patients with empirically treated or cytologically confirmed PCP, hospitalized during 1987 to 1990 were retrospectively reviewed. Patients were classified by insurance status: self-pay (n = 56), Medicaid (n = 254), or private insurance, including health maintenance organizations and Medicare (n = 580). Primary outcomes were the use and timing of bronchoscopy, the type and timing of PCP therapy, and in-hospital mortality. The results indicate that Medicaid patients were less likely than privately insured patients to undergo bronchoscopy (relative odds = 0.61; 95% CI = 0.40, 0.93; p = 0.02) or to have their diagnosis of PCP confirmed (relative odds = 0.51; 95% CI = 0.33, 0.77), after adjusting for patient, severity of illness, and hospital characteristics. Medicaid patients were approximately three-fourths more likely than privately insured patients (relative odds = 1.73; 95% CI = 1.01, 2.96; p = 0.04) to die in-hospital, after adjusting for patient, severity of illness, and hospital characteristics. However, with further adjustment for confirmation of PCP, Medicaid patients no longer had a significantly higher likelihood of dying in-hospital. We conclude that Medicaid patients are less likely to receive diagnostic bronchoscopy than privately insured or self-insured patients, more likely to be empirically treated for PCP, and more likely to die in-hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Empirically treated Pneumocystis carinii pneumonia in Los Angeles, Chicago, and Miami: 1987-1990.

Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases, persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP.

The learning curve for AIDS-related Pneumocystis carinii pneumonia: experience from 3,981 cases in Veterans Affairs Hospitals 1987-1991.

Previous studies have found lower mortality rates for AIDS-related Pneumocystis carinii pneumonia (PCP) in hospitals with higher levels of experience with PCP. It is not known if patients are selectively referred to better hospitals or if there is a learning curve whereby outcomes improve as physicians gain experience in treating PCP. We assessed cases of PCP at 140 Veterans Administration (VA) Medical Centers in the United States. During 1987-1991, 3,981 patients were hospitalized with first-episode AIDS-related PCP. Mortality at 30 days after admission. For these 3,981 hospitalizations at the 140 study hospitals, the 30-day mortality was 19%. Logistic regression models indicate that older age, race, geographic area, earlier year of treatment, hospitalization in the previous 12 months, and lower levels of hospital experience with AIDS were significant predictors of mortality at 30 days after admission. Compared with hospitals that had treated three cases or fewer of first-episode PCP, the odds of mortality at 30 days at hospitals that treated > 50 cases of first-episode PCP were 0.73 (95% confidence interval 0.58-0.91), after controlling for differences in characteristics of the patients, year, and region. Mortality of patients with AIDS-related PCP decreases as VA hospitals gain experience. Longitudinal analyses over a 5-year period suggest that a learning curve best explains this finding.

Tool use and team success in continuous quality improvement: are all tools created equal?

This article describes a study that used data from the Department of Veterans Affairs Health Services' Western Region TQI Registry to compare the relationship between theory tools, data tools, and perceived quality improvement. No significant bivariate relationship between the use of theory tools and perceived improvement was found, but there was a positive and significant relationship between the use of data tools and perceived improvement. The use of data management tools by all teams in the study was much lower than expected.

A rapid preadmission method for predicting inpatient course of disease for patients with HIV-related Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) has been the most common reason for hospitalization and the most common cause of death for persons with HIV infection. Hospital mortality rates for PCP range from 10 to 60%. Studies that evaluate differences in hospital mortality rates must control for differences in patient severity of illness. We developed a simple staging system for categorizing severity of illness in patients with PCP. We analyzed the relation between clinical factors and in-hospital mortality for 576 hospitalized patients with HIV-related PCP treated at 56 hospitals for the years 1987 to 1990. Four stages of PCP could be identified based on three routinely measured clinical variables: alveolar-arterial oxygen difference, total lymphocyte count, and body mass index. The mortality rate increased by stage: 1% for Stage 1, 8% for Stage 2, 23% for Stage 3, and 48% for Stage 4. The four-stage severity system compared well with previous models developed for AIDS and for PCP, and is easier to use in clinical practice. Our staging system identifies patients with a high and low risk of in-hospital death upon admission. Physicians may benefit from consideration of PCP stage in deciding on management strategies. In addition, researchers involved in clinical trials of new agents for PCP might consider stratification by PCP stage in order to define homogenous groups.

Free radicals enhance basal release of D-[3H]aspartate from cerebral cortical synaptosomes.

Excessive generation of free radicals has been implicated in several pathological conditions. We demonstrated previously that peroxide-generated free radicals decrease calcium-dependent high K(+)-evoked L[3H]-glutamate release from synaptosomes while increasing calcium-independent basal release. The present study evaluates the nonvesicular release of excitatory amino acid neurotransmitters, using D-[3H]aspartate as an exogenous label of the cytoplasmic pool of L-glutamate and L-aspartate. Isolated presynaptic nerve terminals from the guinea pig cerebral cortex were used to examine the actions and interactions of peroxide, iron, and desferrioxamine. Pretreatment with peroxide, iron alone, or peroxide with iron significantly increased the calcium-independent basal release of D-[3H]aspartate. Pretreatment with desferrioxamine had little effect on its own but significantly limited the enhancement by peroxide. High K(+)-evoked release in the presence of Ca2+ was enhanced by peroxide but not by iron. These data suggest that peroxide increases nonvesicular basal release of excitatory amino acids through Fenton-generated hydroxyl radicals. This release could cause accumulation of extracellular excitatory amino acids and contribute to the excitotoxicity associated with some pathologies.

Modification of monoclonal antibody carbohydrates by oxidation, conjugation, or deoxymannojirimycin does not interfere with antibody effector functions.

Site-specific attachment of metal chelators or cytotoxic agents to the carbohydrate region of monoclonal antibodies results in clinically useful immunoconjugates [Doerr et al. (1991) Ann Surg 214: 118, Wynant et al. (1991) Prostate 18: 229]. Since the capacity of monoclonal antibodies (mAb) to mediate tumor cell lysis via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) may accentuate the therapeutic effectiveness of immunoconjugates, we determined whether site-specific modification of mAb carbohydrates interfered with these functions. The chemical modifications examined consisted of periodate oxidation and subsequent conjugation to either a peptide linker/chelator (GYK-DTPA) or a cytotoxic drug (doxorubicin adipic dihydrazide). mAb-associated carbohydrates were also modified metabolically by incubating hybridoma cells in the presence of a glucosidase inhibitor deoxymannojirimycin to produce high-mannose antibody. All four forms (unaltered, oxidized, conjugated and high-mannose) of murine mAb OVB-3 mediated tumor cell lysis via CDC. Similarly, equivalent ADCC was observed with native and conjugated forms of mAb OVB-3 and EGFR.1. ADCC was achieved with different murine effector cells such as naive (NS), poly (I*C)- and lipopolysaccharide-stimulated (SS) spleen cells, or Corynebacterium-parvum-elicited peritoneal cells (PEC). All murine effector cell types mediated tumor cell lysis but differed in potency such that PEC > SS > NS. Excellent ADCC activity was also demonstrable by human peripheral blood mononuclear cells with OVB-3-GYK-DTPA and high-mannose OVB-3 mAb. ADCC activity was detectable in vivo: both native and conjugated OVB-3 inhibited growth of OVCAR-3 xenografts in nude mice primed with C. parvum. In conclusion, modification of mAb carbohydrates did not compromise their in vivo or in vitro biological functions. Therefore, combination therapy using immunomodulators to enhance the effector functions of site-specific immunoconjugates could be seriously contemplated.

Improved outcomes in intensive care units for AIDS-related Pneumocystis carinii pneumonia: 1987-1991.

Respiratory failure due to Pneumocystis carinii pneumonia (PCP) is the most common complication requiring an intensive care unit (ICU) for persons with AIDS. In this study, we evaluated patterns of ICU use for ICU patients with first-episode PCP in 15 Veterans Administration Medical Centers from 1987 to 1991. Twelve percent of all patients with PCP received care in the ICU. The survival rates improved steadily during these years. Although there was little variation in the relative frequency of ICU use, the effectiveness of ICU use appeared to improve over time. In the more recent years, relatively more survivors and relatively fewer nonsurvivors received care in an ICU. Changes in medical practice such as adjunctive use of steroids for severe cases of PCP and more effective use of scarce resources may account for the improved survival rates for patients with PCP who are treated in an ICU.

Effect of oxidative stress on excitatory amino acid release by cerebral cortical synaptosomes.

Previous studies in our laboratory have suggested that an oxidation reaction is responsible for the actions of free radicals to decrease synaptic potentials. Recently we observed that free radicals both decreased depolarization-induced vesicular release and enhanced basal, nonvesicular release of the excitatory amino acid, [3H]L-glutamate. In order to evaluate the contribution of oxidative reactions to this latter effect, we evaluated the actions of the oxidizing agent chloramine-T on synaptosomal release of excitatory amino acids, using [3H]D-aspartate as the exogenous label. Basal and depolarization evoked [3H]D-aspartate release were calcium-independent and nonvesicular. Chloramine-T pretreatment significantly increased basal release, while having no effect on high K(+)-evoked release. These data suggest that an oxidative process can mimic the free radical increase of basal release, as well as the decrease in synaptic potentials. On the other hand, the calcium-independent-evoked release may involve a different mechanism. Our results demonstrate that under basal, nondepolarizing conditions, oxidative stress exerts an adverse effect on the presynaptic nerve terminal, resulting in an increased release of potentially damaging excitatory amino acid neurotransmitters.

Use of traditional and modern health services by Laotian refugees.

Although refugee health care emerged as a special interest in the United States following the influx of almost a million Southeast Asians since 1975, few studies have been done of the influence of refugee traditions on the use of Western medical services. The illness patterns, medical beliefs, and health care behavior of a Southeast Asian refugee group, the Mien from Laos are described in this study. A cohort of 119 Mien refugees living in Richmond, California, was observed for a 6-month period. In-home interviews were undertaken about all episodes of ill health, including treatment and health care decisions. This study shows that the Mien integrate traditional healing beliefs and practices with the use of American health services. Such findings are important because the increasing cultural diversity in the United States, particularly in Western states, necessitates that health care professionals understand the importance of cultural factors for access to and the use of health care by all patients including refugees and other immigrant groups.

Peroxide effects on [3H]L-glutamate release by synaptosomes isolated from the cerebral cortex.

Basal (non-depolarized) and high K(+)-stimulated [3H]L-glutamate release in the presence and absence of Ca2+ were assessed using presynaptic nerve terminals (synaptosomes) isolated from the cerebral cortex of the guinea pig. Basal glutamate release was found to be Ca(2+)-independent and was significantly increased following treatment with hydrogen peroxide (H2O2). On the other hand, depolarization-induced release had both a Ca(2+)-dependent and Ca(2+)-independent component. Both components of stimulated release were suppressed by H2O2. In fact, Ca(2+)-dependent evoked release was virtually eliminated by H2O2 pretreatment. The data suggest that H2O2 exerts a differential effect on the neurochemical mechanisms involved in basal and stimulated glutamate release at the presynaptic nerve terminal.