Exacerbation of thrombotic events by diesel exhaust particle in mouse model of hypertension

Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15 μg/mouse) or saline. 24 h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P<0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO? was decreased, and PaCO? increased in DEP-treated HT mice compared to NT mice treated with DEP (P<0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P<0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1-1 μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25-1 μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by DEP are exacerbated by hypertension in mice. Our findings, therefore, provide a possible plausible explanation for the cardiovascular morbidity and mortality accompanying urban air pollution.     

Orbitofrontal dysfunction in a monozygotic twin discordant for postpartum affective psychosis: a functional magnetic resonance imaging study

BACKGROUND: Incomplete concordance for psychosis in monozygotic (MZ) twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. In this case study, we consider childbirth a landmark in the onset of psychotic symptoms, leading to the diagnosis of puerperal psychosis and then to bipolar/schizoaffective disorder. At the end of the third trimester, there is a sudden drop in estrogen, which exerts prominent effects on the serotonergic system in the orbitofrontal cortex (OFC). OBJECTIVES: The purpose of the present study was to investigate OFC activation during emotional processing in MZ twins discordant for affective psychosis. METHODS: Blood-oxygen-level-dependent activation using functional magnetic resonance imaging was measured during the passive viewing of emotional film excerpts. RESULTS: Consistent with our hypothesis, a significant locus of activation was found in the left OFC in the normal MZ twin, but not in the psychosis MZ twin. CONCLUSIONS: The personality changes noted in the psychosis MZ twin (postpartum psychosis) may be related to dysfunctional OFC. Ms J's childbirth may have triggered the onset of psychotic symptoms, leading to the diagnosis of bipolar or schizoaffective disorder.     

Learning and Retaining Normal Radiographic Chest Anatomy: Does Preclinical Exposure Improve Student Performance?

RATIONALE AND OBJECTIVES: Although most would concur that preclinical exposure to radiology is a desirable goal, specific learning objectives have been more difficult to delineate. It is also important to assess what is learned and to determine how well it is retained or "retrievable." This study was developed in an attempt to document the extent to which specific measures of preclinically acquired knowledge may be retained and retrieved for later clinical application. MATERIAL AND METHODS: The Anatomic Structure Identification Quiz (ASIQ, or Quiz), previously described in Feigin et al (Academic Radiology 2005) was administered to 236 medical students at the conclusion of the required second-year course, as a 10-item written Quiz based on a projected frontal and lateral chest image. The 10-item Quiz was also administered to 555 senior medical students (194 of which had been included in previous work) on the first day of the Uniformed Services University of the Health Sciences basic radiology elective. Finally, the identical Quiz was completed by 74 of these 555 senior medical students at the conclusion of the academic portion of the elective, approximately 3 weeks after the administration of the first quiz. RESULTS: The second-year students scored a mean of 7.15 points of a possible 10 points with a standard deviation (SD) of 1.42. The senior students completing the quiz at the beginning of the elective scored an average of 4.42 (SD 1.34) compared to a score of 8.65 (SD 1.24) 3 weeks later. CONCLUSION: Long-term recall of specific radiologic structures learned in the second year of medical school was poor despite evidence documenting good initial (short-term) retention of tested information. However, after a brief review, consisting of the Quiz itself, followed by 3 weeks of general radiology emphasizing abnormal chest imaging, the senior students demonstrated a near doubling of their ability to correctly identify these structures, as well as an improvement compared with scores obtained during the second year. Thus the value of a preclinical course in radiology may be not only to teach principles of radiology and to stimulate interest in the discipline, but also, by repetition and reinforcement, to facilitate and possibly improve later recall and retention of important radiographic material.     

Comparison of outcomes in patients aged <75, 75 to 84, and ≥ 85 years with ST-elevation myocardial infarction (from the ACTION Registry-GWTG)

ST-segment elevation myocardial infarction (STEMI) is common in older adults and has high age-related mortality. We describe contemporary STEMI care using the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Network Registry-Get With The Guidelines (ACTION-GWTG) database. Patients with STEMI (n = 30,188) from 285 ACTION-GWTG sites from January 1, 2007 to June 30, 2008 were grouped by age (<75, 75 to 84, and ≥ 85 years) to compare baseline characteristics, reperfusion, and in-hospital outcomes. In this population, 79.7% (24,070) were <75 years old, 14.2% (4,273) were 75 to 84 years old, and 6.1% (1,845) were ≥ 85 years old (the oldest old). Compared to younger patients, the oldest-old patients (median age 88 years, interquartile range 86 to 91) were more often women, had more hypertension, and end-organ co-morbidity (heart failure and stroke, p <0.0001 for all). More than 42% of the oldest old were also cited as having contraindications to reperfusion, but with absolute or relative contraindications noted in only 10%, and patient preference was the most common reason indicated (45%). Even in reperfusion-eligible patients, the oldest old were less likely to receive it. Although patients who received reperfusion had better outcomes than those who did not, this was significant only for younger patients (< 75 years old, odds ratio 0.58, confidence interval 0.40 to 0.84). In conclusion, > 42% of the oldest old have reported contraindications to reperfusion, with neither mortality benefit nor harm in those who receive it. Disparities in process of care and co-morbidity may explain these observational findings. Whether efforts to optimize patient selection and initiate reperfusion therapy can improve outcomes in the oldest old with STEMI is unknown.     

Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.     

Gonorrhoea surveillance system in France: 1986-2000

OBJECTIVE: The objectives of this study were to monitor epidemiologic trends in Neisseria gonorrhoeae (NG) infections and to assess antimicrobial resistance patterns of NG. METHODS: RENAGO, a voluntary-based laboratory surveillance system, including private and public laboratories, was set up in France in 1986. Every NG strain isolated by the participating laboratories was sent to the National Reference Center, Institut Alfred Fournier, Paris, where susceptibility to 6 antibiotics was tested. These laboratories reported monthly numbers of positive NG isolates and associated epidemiologic data. Because the number of laboratories varied every year, the average number of NG isolates per laboratory per year was computed to monitor annual trends in gonorrhea incidence. RESULTS: The average number of NG isolated per laboratory per year decreased steadily from 10.6 in 1986 to 0.6 in 1997 but then yearly increased and reached 1.9 in 2000. Increasing gonorrhea was observed mostly in men and in the Paris area. The proportion of rectal strains increased significantly from 0.9% in 1986 to 9.2% in 2000. From 1998 to 2000, 5.3% of the isolates had reduced susceptibility or were resistant to ciprofloxacin, 7.3% were PPNG strains and 27.4% were resistant to tetracycline, 18.5% had a reduced susceptibility to thiamphenicol, and 1 strain was resistant to the latter. Neither strain was resistant to ceftriaxone or to spectinomycin. CONCLUSION: From 1998 to 2000, gonorrhea markedly increased in France and seemed to affect mainly gay men in Paris, which suggests relapses to risky sexual behaviors and highlights the need for strengthening prevention. During the same period, NG ciprofloxacin resistance has sharply increased and should be carefully monitored because of the wide use of ciprofloxacin single-dose treatment.     

A combined chemical-physical treatment for herpes simplex lesions in guinea pigs

Summary Determination of the effectiveness of chemical treatments for Herpes simplex type 2 infections has generally relied on a reduction in the rate of mortality. A more natural progression of the disease is seen when nonprogressive cutaneous lesions are induced. Treatment of characteristic cutaneous lesions with ultrasound alone, a cream compound designated Herpigon alone, or a combination of ultrasound and Herpigon were compared to determine the time required for lesions to heal and the amount of virus recoverable from treated lesions. Results indicate that the use of Herpigon alone or in combination with ultrasound resulted in a significant reduction in the time required for the lesions to heal. A comparison of the amount of virus present in treated lesions indicated that the combined treatment was most effective in reducing the amount of recoverable virus.