Morphologic observations of brain tumors in PD4 hamsters induced by four strains of Avian Sarcoma Virus

Summary Brain tumors were induced in inbred PD4 hamsters with each of four strains of Avian Sarcoma Virus: CT-559, Bratislava-77, Schmidt-Ruppin, and Bryan.Based on light and electron microscopic observations the neoplastic tissues found in these tumors were identified as: (1) glial, (2) a distinctive large cell, and (3) sarcomatous.The glial neoplasms consisted almost entirely of masses of astrocytes in a subependymal position.The large cell tissue was a striking feature in some of the tumors. Although the cell of origin for this tissue could not be positively identified, certain features suggested that these cells were derived from glia.The cerebral sarcomas occurred as small nodules near the pial surface or occasionally as large intracerebral masses.Replicating virus was not seen in any of the tumors.Supported by NCI research grant CA 11898, NINDS Neuropathology Training grant NS 05212, and NINDS Fellowship 1 F 11 NS 2261 (D.D.B.).Presented in part at the 48th Annual Meeting of the American Association of Neuropathologists in Chicago, Illinois, June, 1972.     

The role of support in relation to recovery from breast surgery

The relationship between support and short-term recovery from breast surgery was examined retrospectively in 151 female breast cancer patients who were 3–12 months postoperative. Subjects were interviewed regarding the extent to which 3 forms of support (social, professional, financial) were available. Two indices, representing physical recovery and psychological adjustment, were generated. Patient characteristics (age, education, prior health status, and life stress following surgery) and clinical indicators of disease severity (stage, type of mastectomy, adjunct therapy, and time elapsed since surgery) were controlled. Social and professional support were significantly positively related to psychological adjustment. Financial support was significantly positively related to physical recovery. Implications of these findings for future research are discussed.     

Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients

BACKGROUND: Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients. METHODS: Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine. The primary endpoint for this noninferiority study was the proportion of patients (response rate) with an HIV RNA load <400 copies/mL at week 48. RESULTS: Response rates at week 48 were 86% and 85% on the ATV300/RTV and ATV400 regimens, respectively (difference estimate [95% confidence interval] = 1.5 [-8.2 to 11.1]). There were 3 and 10 patients with virologic failure in the ATV300/RTV and ATV400 groups, respectively. One patient (ATV400) developed phenotypic resistance to ATV associated with an I50L substitution. Adverse event-related discontinuations were 8% among ATV300/RTV-treated patients and <1% among ATV400-treated patients. Plasma lipid elevations were low with both regimens. Both regimens were well tolerated. CONCLUSIONS: These findings demonstrate the safety and efficacy of the ATV300/RTV regimen and confirm the safety and efficacy of ATV400 in an ARV-naive patient population.     

Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo

Enteropathogenic Escherichia coli (EPEC) infection disrupts tight junctions (TJs) and perturbs intestinal barrier function in vitro. E. coli secreted protein F (EspF) is, in large part, responsible for these physiological and morphological alterations. We recently reported that the C57BL/6J mouse is a valid in vivo model of EPEC infection as EPEC colonizes the intestinal epithelium and effaces microvilli. Our current aim was to examine the effects of EPEC on TJ structure and barrier function of the mouse intestine and to determine the role of EspF in vivo. C57BL/6J mice were gavaged with approximately 2 x 10(8) EPEC organisms or PBS. At 1 or 5 days postinfection, mice were killed and ileal and colonic tissue was mounted in Ussing chambers to determine barrier function (measured as transepithelial resistance) and short circuit current. TJ structure was analyzed by immunofluorescence microscopy. Wild-type (WT) EPEC significantly diminished the barrier function of ileal and colonic mucosa at 1 and 5 days postinfection. Deficits in barrier function correlated with redistribution of occludin in both tissues. Infection with an EPEC strain deficient of EspF (delta espF) had no effect on barrier function at 1 day postinfection. Furthermore, delta espF had no effect on ileal TJ morphology and minor alterations of colonic TJ morphology at 1 day postinfection. In contrast, at 5 days postinfection, WT EPEC and delta espF had similar effects on barrier function and occludin localization. In both cases this was associated with immune activation, as demonstrated by increased mucosal tumor necrosis factor-alpha levels 5 days postinfection. In conclusion, these data demonstrate that WT EPEC infection of 6-8-week-old C57BL/6J mice (1) significantly decreases barrier function in the ileum and colon (2) redistributes occludin in the ileum and colon and (3) is dependent upon EspF to induce TJ barrier defects at early, but not late, times postinfection.     

Mercury-induced cognitive impairment in metallothionein-1/2 null mice

Metallothioneins are central for the metabolism and detoxification of transition metals. Exposure to mercury during early neurodevelopment is associated with neurocognitive impairment. Given the importance of metallothioneins in mercury detoxification, metallothioneins may be a protective factor against mercury-induced neurocognitive impairment. Deletion of the murine metallothionein-1 and metallothionein-2 genes causes choice accuracy impairments in the 8-arm radial maze. We hypothesize that deletions of metallothioneins genes will make metallothionein-null mice more vulnerable to mercury-induced cognitive impairment. We tested this hypothesis by exposing MT1/MT2-null and wild-type mice to developmental mercury (HgCl₂) and evaluated the resultant effects on cognitive performance on the 8-arm radial maze. During the early phase of learning metallothionein-null mice were more susceptible to mercury-induced impairment compared to wildtype mice. Neurochemical analysis of the frontal cortex revealed that serotonin levels were higher in metallothionein-null mice compared to wild-type mice. This effect was independent of mercury exposure. However, dopamine levels in mercury-exposed metallothionein-null mice were lower compared to mercury-exposed wild-type mice. This work shows that deleting metallothioneins increase the vulnerability to developmental mercury-induced neurocognitive impairment. Metallothionein effects on monoamine transmitters may be related to this cognitive effect.     

A new distensibility technique to measure sphincter of Oddi function

Background Evaluation of the biliary tract is important in physiological, pathophysiological, and clinical studies. Although the sphincter of Oddi (SO) can be evaluated with manometry, this technique has several limitations. This may explain the difficulties in identifying pathophysiological mechanisms for dysfunction of the SO and in identifying patients who may benefit from certain therapies. To encompass problems with manometry, methods such as the functional lumen imaging probe (FLIP) technique have been developed to study GI sphincters. This study set about miniaturising the FLIP probe and validating it for measurements in the SO. In order to get a better physiological understanding of the SO the aims were to show the sphincter profile in vivo and motility patterns of SO in pilot studies using volunteers that were experiencing biliary type pain but had normal SO manometry. Methods The SO probe was constructed to measure eight cross‐sectional areas (CSA) along a length of 25 mm inside a saline‐filled bag. To validate the technique for profiling the SO, six perspex cylinders with different CSAs were measured nine times to assess reproducibility and accuracy. Key Results Reproducibility and accuracy for these measurements were good. The probe performed well in bench tests and was therefore tested in four humans. The data indicated that it was possible to make distensions in the human SO and that a geometric sphincter profile could be obtained. Conclusions & Inferences The probe will in future studies be tested for diagnostic purposes related to sphincter of Oddi diseases.     

Myocardial infarction with unusual presentation of otalgia: a case report

A rare case of a patient with unusual symptoms of earache and sore throat for cardiac ischemia is presented. A diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) was made based on initial elevation of troponin and an abnormal electrocardiograph (ECG). Percutaneous coronary intervention (PCI) performed with stent placement in the occluded coronary vessel was followed by a decrease in troponin level and complete resolution of the ear and throat pain and patient recovery from cardiac ischemia.