Increased circulating CSF-1 (M-CSF) in myeloproliferative disease: association with myeloid metaplasia and peripheral bone marrow extension

Myeloproliferative disease (MPD) is heterogeneous in phenotypic expression and may display features consistent with expansion and activation of the monocyte/macrophage population during its course. The role of colony-stimulating factor-1 (CSF-1) in the pathophysiology of MPD was investigated by measuring circulating CSF-1 levels and examining their relationship to disease phenotype. Serum CSF-1 concentrations, measured by radioimmunoassay, were elevated in all MPD phenotypes. CSF-1 levels differed significantly between groups of patients with essential thrombocythemia, polycythemia vera, and postpolycythemic or agnogenic myeloid metaplasia (in ascending order). CSF-1 serum levels were positively correlated with spleen size and the degree of peripheral bone marrow extension, determined by scintigraphy using a macrophage-seeking isotope. There was no correlation between CSF-1 concentration and circulating levels of erythrocytes, neutrophils or platelets, or the presence of bone marrow fibrosis. Elevated serum CSF-1 levels appear to be associated with an expanded monocyte/macrophage population in MPD. In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD.     

3T multiparametric MR imaging,PIRADSv2-based detection of index prostate cancer lesions in the transition zone and the peripheral zone using whole mount histopathology as reference standard

Abdominal Radiology - To evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount...     

Extraction Atherectomy for Recently Occluded Saphenous Vein Grafts: A Retrospective Study

BACKGROUND: Over 300,000 coronary artery bypass operations are performed annually in the U.S., in which saphenous vein grafts remain the most often utilized conduit for myocardial revascularization. Still, the relatively short life-span of reverse saphenous vein grafts (SVG) demands that revascularization techniques be developed for SVG occlusions. Extraction atherectomy (EA) as a pre-treatment to percutaneous transluminal coronary angioplasty (PTCA) may offer advantages to PTCA alone in the treatment of these lesions. While a randomized study would best define the potential advantages of this treatment strategy, a retrospective comparison to historical data may provide some practical insights. PATIENTS AND METHODS: One hundred and six patients treated with EA + PTCA (Group 1) were retrospectively compared to a historical subset of 101 patients treated with PTCA alone (Group 2). Both groups presented with similar clinical profiles with respect to gender, age, graft age, percent diameter stenosis, and location of the target lesion. However, Group 1 had a significantly higher incidence of pre-procedure class III-IV angina than did Group 2 (92.4% vs. 70.3%, p < 0.002), and more recent occlusions. Both groups were compared at one year for the presence of angina, myocardial infarction, and death. Chi-square analysis was performed on the categorical variables. RESULTS: At one-year follow-up, 62.1% of the Group 1 patients were free from cardiac events (defined as absence of angina, myocardial infarction or death) and 58.9% of the Group 2 patients were event free (p = 0.78). A total of 27.0% of the Group 1 patients suffered from class I or Il angina compared to 35.9% of the Group 2 patients (p = 0.40). A total of 10.8% of the Group 1 patients had suffered a myocardial infarction compared to 28.2% of the Group 2 patients (p = 0.06). A total of 2.7% of the Group 1 patients had died compared to 10.5% of the Group 2 patients (p = 0.16). CONCLUSIONS: Patients with recently occluded SVGs (within 3 months) and refractory angina (class III or IV) treated with EA + PTCA have a similar clinical outcome at 1 year follow-up to a historical population treated with PTCA alone, despite the higher incidence of class III-IV angina, and more recent occlusions upon presentation. However, 1-year follow-up results reveal a trend towards less frequent myocardial infarctions for patients treated with EA + PTCA than the historical group of patients treated with PTCA alone (p = 0.06).     

Effects of daily melatonin injections on female reproduction in the white-footed mouse, Peromyscus leucopus

Seventy laboratory-reared (16L:8D at 21°) Peromyscus leucopus were injected daily for 7 weeks with either saline, 0.5, 5.0, or 50 μg of melatonin at either 2 or 12 hr into the photophase. Mice injected with 50 μg at 12 hr exhibited a substantial decrease (P < 0.01) in relative reproductive tract weight (2.3 ± 0.4 mg/g body wt) when compared to saline injected animals (4.6 ± 0.9). Seven out of the nine melatonin-treated mice also exhibited an imperforate vagina. A lesser effect was noted at lower melatonin concentrations. No regression occurred in mice injected 2 hr into the photophase. Thermoregulatory characters (nesting, brown fat, winter molt) were not affected by melatonin injections. In a second experiment 49 mice were injected with 50 μg of melatonin at either 7.5, 10, 14, 15, 18, or 23 hr after lights on. A gradual antigonadal effect was observed with a peak during late photophase. Mice injected during early scotophase (18 hr) exhibited little antigonadal effects of melatonin, but animals injected at 23 hr had reproductive tract weights which were considerably less (P < 0.05).     

Predictors of failure to attend scheduled mammography appointments at a Public Teaching Hospital

Objective: To identify patient, institutional, and physician characteristics that predict failure to attend scheduled mammography appointments. Design: Retrospective chart review. Setting: Medicine clinic at an urban public teaching hospital. Patients: All 907 women aged 40 years and more scheduled for mammography from March 1990 to June 1991. Measurements and main results: The main outcome measure was whether a woman kept her scheduled mammography appointment. Potential predictor variables included patient age, race, marital status, and insurance status; waiting interval to obtain a mammography appointment; and physician gender, level of training, country of training, and native language. The rate of failed mammography appointments was 23%. Univariate analysis showed that appointment failure was associated with age (p=0.03), with the lowest failure rates (19%) among women aged 60 years and more. Appointment keeping varied significantly by race (p=0.01), largely because of the higher failure rate among Native American women (36%). Insured women had a failure rate of 22% vs 33% for uninsured women (p=0.01). The rate of failed appointments varied significantly by waiting interval (p=0.05), with a peak failure rate of 27% for appointments scheduled 14–27 days in advance. None of the physician variables was associated with appointment failure. Multivariate analysis confirmed these results. Conclusions: Interventions to improve completion of breast cancer screening should include additional efforts targeted at groups with high rates of appointment failure, such as women under the age of 60, the uninsured, and Native Americans. Long waiting intervals to obtain mammography appointments may decrease compliance. Presented in part at the annual meeting of the Society of General Internal Medicine, Washington, DC, April 30, 1992. Supported by research grant CA 52994 from the National Cancer Institute, Bethesda, Maryland. Dr. Margolis was supported by an American Cancer Society Cancer Control Career Development Award for Primary Care Physicians. Dr. Lurie is a Henry J. Kaiser Family Foundation Scholar in General Internal Medicine.     

Why Do Patients of Female Physicians Have Higher Rates of Breast and Cervical Cancer Screening?

OBJECTIVE: Women are more likely to receive breast and cervical cancer screening if they see female physicians. We studied whether this is due to differences between male and female physicians, or to differences in their patients. SETTING: Large midwestern, independent practice association style of health plan. DESIGN: We surveyed male and female primary care physicians matched for age and specialty and a stratified random sample of three of each physician's women patients. Physicians reported on their practice setting, their attitudes and practices regarding prevention, and their comfort and skill with various examinations. Patients reported on their sociodemographic characteristics, their attitudes and practices regarding prevention, and their preferences for physician gender. Claims data were used to calculate mammography and Pap smear screening rates for the physicians PARTICIPANTS: We studied 154 female and 190 male internists and family physicians and 794 of their patients. MEASUREMENTS AND MAIN RESULTS: We compared the responses of male and female physicians and their patients and used multivariable analysis to identify the patient and physician factors that accounted for the differences in screening rates between male and female physicians. Female physicians were more likely to ask new patients about components of prevention, to believe in the effectiveness of mammography, to feel more personal responsibility for ensuring that their patients received screening, and to report more comfort in performing Pap smears and breast examinations. Patients of female physicians were more educated and less likely to be married, but did not differ in other sociodemographic characteristics. They had similar attitudes and practices regarding prevention, except that patients of male physicians were more likely to smoke. Significantly more patients of female physicians preferred a female for some component of care. In multivariable analyses, practice organization, patient preference for a female physician, and prevention orientation of female physicians accounted for up to 40% of screening rate differences between female and male physicians for Pap smears, and 33% for mammography. CONCLUSIONS: Differences in beliefs of male and female physicians and patient preference for a female provider contribute independently to the higher rate of breast and cervical cancer screening by female physicians.     

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.