Contrast-enhanced magnetic resonance angiography of carotid arterial wall in pigs

This study was designed to investigate the effects of contrast agents on MR images of balloon-injured carotid arteries containing atherosclerotic-like lesions. We have evaluated an intravascular contrast agent, MS-325 (METASYN INC., Cambridge, MA) and an extra-vascular contrast agent, Optimark, (Mallinckrodt Medical Inc., St. Louis, MO) on MR angiograms obtained 4 weeks after balloon hyperinflation-induced injury of the left common carotid artery in 12 hypercholesterolemic minipigs. High in-plane resolution (.8 × .4 mm²), thin slice (1 mm) time-of-flight gradient echo sequences were used to acquire the MR angiographic images. Vascular lumen definition was compared before and after a single bolus intravenous injection of a contrast agent. Digital subtraction angiograms were obtained from all pigs after MR imaging. High grade stenosis developed in 1 of the 12 pigs and five pigs had complete occlusion of the injured vessel. The remaining pigs exhibited essentially no visible stenoses as assessed either by MR angiography or digital subtraction angiography. The vessel walls of the stenosed and occluded vessels were visible after the injection of either intravascular or extravascular contrast agent. Histologic analyses showed well developed neovascularization in the neointima or occlusive thrombosis. We conclude that the observed contrast-enhanced vessel wall is caused by an increased vascular supply associated with thrombosis and neointimal thickening that leads to an accumulation of contrast agent in the abnormal vessel walls after the injection of the T1-shortening paramagnetic contrast agent.     

Understanding the development of the concept of suicide through the use of early memory technique

Early memories of adults were examined to assess the understanding of the concept of suicide from childhood experiences. Two sets of early memories were gathered in which subjects recalled their earliest suicide memory and their earliest suicidal thought. Content analysis of these memories revealed that between the ages of 8 and 12 initial exposure to suicide occurs predominately through impersonal means; at this level of suicide understanding, uncertainty surrounds the motivating factors of suicide. It was found that at approximately age 14, a mature adult conception of suicide existed. This was a time period in which individuals, for the first time, were beginning to think about killing themselves as a solution to personal conflict or emotional turmoil in their life. Findings support research relating to the areas of death conception and levels of cognitive functioning in children. Further areas of investigation are outlined.     

Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival.

PURPOSE: In a study of 208 meningiomas, we found a high incidence of loss of heterozygosity (LOH) on chromosome 10 in benign (73.4%), atypical (80.0%), and malignant (86.7%) tumors. A large percentage of the benign and atypical tumors and an increasing percentage of malignant tumors had LOH on multiple loci (43.9%, 45%, and 66.7%, respectively). The high incidence of LOH occurring early in meningioma progression suggests that LOH at individual alleles may serve as a marker of clinically relevant alterations useful for patient diagnosis, the subclassification of tumors, and/or the treatment of patients. EXPERIMENTAL DESIGN: To test this, we examined 208 sporadic and recurrent meningiomas of all grades for correlations between LOH at 11 markers on chromosome 10 and tumor location, histology, and grade and patient race, gender, age, recurrence, and survival. RESULTS: Several significant correlations were found. The data indicate that genetic differences occur not only between tumors of different grade, but also between tumors of the same grade, and therefore may be useful to define genetic subsets with clinical implications. LOH at D10S179 (P = 0.001) or D10S169 (P = 0.004) is most likely present in higher-grade meningiomas and, when present in benign tumors, may signify sampling error or a morphologically benign but biologically aggressive tumor. Furthermore, LOH at D10S209 (P = 0.06) and D10S169 (P = 0.01) may predict shorter survival and/or higher rates of recurrence, respectively, in tumors with benign or malignant histology. CONCLUSIONS: We conclude that these chromosome 10 markers deserve further testing as unfavorable prognostic indicators for meningioma patients.     

Central levodopa metabolism in Parkinson's disease after administration of stable isotope—labeled levodopa

We report the use of a new stable isotope–labeled form of levodopa (LD) to examine in vivo central LD metabolism in Parkinson's disease (PD). Eight patients representing a wide spectrum of disease severity were administered 50 mg of carbidopa orally followed in 1 hour by an intravenous bolus of 150 mg of stable isotope–labeled LD (ring-1′,2′,3′,4′,5′,6′-¹³C6). Serial blood samples were taken every 30 to 60 minutes and a lumbar puncture was performed 6 hours after the infusion. The average percentage of labeled homovanillic acid (HVA) in lumbar cerebrospinal fluid (CSF) was 54% (SD, 9%; range, 34–67%). The mean CSF labeled HVA concentration was 34.7 ng/ml (SD, 20.2 ng/ml; range, 11.3–67.9 ng/ml). Area under the curve for labeled serum LD closely predicted CSF labeled HVA concentrations (r = 0.747, p = 0.033). Labeled CSF HVA levels did not significantly correlate with either quality or duration of response to the labeled LD dose. In a similar manner, labeled CSF HVA concentrations were not influenced by duration of disease or previous daily LD dosage. These findings support the hypothesis that levodopa-induced benefit in PD is not severely limited by a defect in central levodopa metabolism.     

Call nights and patient care

OBJECTIVE: To determine whether the timing and number of patients admitted by internal medicine housestaff under a traditional call schedule affect the resource utilization and outcome of care for those patients. DESIGN: Retrospective cohort study, using existing computerized records. SETTING: University-affiliated 340-bed city/county teaching hospital. PATIENTS/PARTICIPANTS: 22,112 patients discharged from the internal medicine service who had been admitted by an on-call first-year resident between January 1, 1980, and December 31, 1987. MEASUREMENTS AND MAIN RESULTS: Admission after 5:00 PM was associated with decreased hospital length of stay (8.1%, p less than 0.0001), but increased total charges (3.1%, p = 0.007). The relative risk of inpatient mortality for patients admitted at night was 1.21 (p = 0.03). Patients of busier housestaff, as indicated by a larger number of on-call admissions, had lower total charges (1.7% decreased per admission) and no change in risk of inpatient mortality. While no linear relation was found between number of admissions and length of stay, analysis of nonlinear effects revealed that length of stay first rises, then falls as interns receive more on-call admissions. CONCLUSIONS: The number and timing of admissions by on-call internal medicine housestaff are significantly related to length of hospital stay, total charges, and likelihood of inpatient mortality at one teaching hospital. These variations should be considered in planning the reform of residency training programs.     

Blunted HPA axis response to stress influences susceptibility to posttraumatic stress response in rats.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with low levels of circulating cortisol, and recent studies suggest that cortisol administration may reduce PTSD symptoms. This study investigated the role of cortisol in the manifestation of anxiety- and fear-like symptoms in an animal model of PTSD. METHOD: Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and nonhabituated exaggerated startle reaction were compared in three strains of rats exposed to predator stress, with and without prior corticosterone treatment. Extreme behavioral changes in both paradigms implied an extreme behavioral response (EBR), representing PTSD-like symptoms. RESULTS: Lewis rats exhibited greater baseline anxiety-like behaviors and greater stress-induced increases in anxiety-like behaviors than Fischer F344 or Sprague-Dawley rats, with only minor corticosterone increases following stress. Prevalence of EBR was 50% among Lewis rats compared with 10% of Fischer F344 and 25% of Sprague-Dawley rats. Administering corticosterone 1 hour before stress exposure reduced the prevalence of EBR from 50% to 8% in the Lewis rats. CONCLUSIONS: These results suggest that a blunted HPA response to stress may play a causal role in this model of PTSD and that this susceptibility may be prevented by administration of cortisol before stress exposure.     

Reduced field of view and undersampled PR combined for interventional imaging of a fully dynamic field of view.

Active catheter imaging was investigated using real-time undersampled projection reconstruction (PR) combined with the temporal filtering technique of reduced field of view (rFOV). Real-time rFOV processing was interactively enabled during highly undersampled catheter imaging, resulting in improved artifact suppression with better temporal resolution than that obtained by view-sharing. Imaging with 64 to 32 projections provided a resolution of 2 x 2 x 8 mm, and four to eight true frames per second. Image artifacts were reduced when rFOV processing was applied to the undersampled images. A comparison with Cartesian rFOV showed that PR image quality is less susceptible to aliasing that results from rFOV imaging with a wholly dynamic outer FOV. Simulations and MRI experiments demonstrated that PR rFOV provides significant artifact suppression, even for a fully dynamic FOV. The near doubling of temporal resolution that is possible with PR rFOV permits accurate monitoring of highly dynamic events, such as catheter movements, and arrhythmias, such as ventricular ectopy.     

Effects of Antioxidants on Oxygen Toxicity in Vivo and Lipid Peroxidation in Vitro

Abstract: Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferoxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferoxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferoxamine (5 and 50 μM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37°. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.     

A breast cancer screening program in a community hospital

Breast cancer screening continues to be underutilized in the United States. The National Cancer Institute has set a goal of increasing screening by the year 2000. The American Cancer Society wants to identify programs that target asymptomatic women and economically disadvantaged women. The purpose of this study was to develop, implement and evaluate a comprehensive breast cancer screening program for women in a community setting. One case of infiltrating ductal carcinoma was detected from the 144 women who participated in the study. Following the educational component, the post test demonstrated a significant increase (p <0.01) in the women's awareness of breast cancer. Additionally, 100% of the women were able to demonstrate breast self examination to an oncology nurse after the educational component of the study. The majority of the women who participated were not economically disadvantaged which sheds new light on the scope of the problem of taking care of the unmet cancer needs of the disadvantaged through outreach programs. However 27% of the women had a household income less than 10,000 with 19% of the women having no insurance and 7% having Medicare/Medicaid. The results of this study could help future programs in bringing breast cancer screening to women in the community setting.Max E. Dodds was Director of Cancer Care Program (deceased); Sharon L. Dowd is Director of Outpatient Heme-Oncology Clinic; Mary Mitchell-Beren is a Heme-Oncology Nurse; Mary Yarbrough is Data Manager; Kelly L. Choi is Oncology Research Coordinator; all in the Department of Heme-Oncology, Hurley Medical Center, Flint, Michigan.     

Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function

Combination chemotherapy with or without radiotherapy has had only modest efficacy in the treatment of primary CNS lymphoma. Median survival of these patients, treated primarily with radiotherapy, is 13 months; 5-year survival is less than 5%. Thirty consecutive non-acquired immune deficiency syndrome patients with primary CNS lymphoma were treated with barrier-dependent chemotherapy using intraarterial mannitol to open the blood-brain barrier (BBB). Follow-up included extensive neuropsychologic testing of all patients. Thirteen patients received cranial radiation 1 to 9 months before referral (group 1). Seventeen patients received initial BBB disruption chemotherapy with subsequent radiation only for tumor progression or recurrence (group 2). The difference in median survivals from diagnosis--17.8 months for group 1 and 44.5 months for group 2--was statistically significant (P = .039). Group 1 survival is comparable with the 20-month median survival of a historical series of patients (n = 208) treated with radiotherapy with or without chemotherapy. Group 2 patient survival represents an advance in the survival of CNS lymphoma and was associated with preservation of cognitive function in six of seven nonirradiated complete responders observed for 1 to 7 years. Patient toxicity was manageable in this intensive therapeutic regimen. In this series, a plateau in survival curves suggests that a major portion of these patients may be cured without the neuropsychologic sequelae associated with cranial radiation.