Primary Lymphoma of Bone: Long Term Results in Patients Treated with Vincristine - Adriamycin - Cyclophosphamide and Local Radiation

Summary

Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%.

Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (Pi), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.2, 0.4, and 0.6 W). In both groups linear relationships were noted between power output and Pi/PCr; the slope of this relationship was used to compare PCr depletion patterns. At rest both groups had similar Pi/PCr ratios (normal subjects 0.12 +/- 0.06, those with heart failure 0.15 +/- 0.03) and pH (normal subjects 7.04 +/- 0.13, those with heart failure 7.10 +/- 0.11). In normal subjects exercise resulted in a progressive increase in Pi/PCr (slope = 1.17 +/- 0.20 Pi/PCr units/W), a reduction in pH only at 0.6 W (0.2 W: 7.03 +/- 0.10, 0.4 W: 7.01 +/- 0.10, 0.6 W: 6.88 +/- 16) and moderate fatigue (0.2 W: 0 +/- 0, 0.4 W: 1.3 +/- 0.5, 0.6 W: 1.9 +/- 0.6). In patients with heart failure exercise resulted in significantly greater fatigue at all workloads (0.2 W: 1.0 +/- 0.5, 0.4 W: 1.9 +/- 0.6, 0.6 W: 2.9 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial baroreceptor control of peripheral vascular resistance in experimental heart failure

Heart failure is known to impair arterial baroreceptor control of heart rate. To determine if baroreceptor control of peripheral vascular resistance is also impaired, heart rate and hind limb vascular responses to phenylephrine and nitroglycerin administration were compared in control dogs and in dogs with heart failure produced by chronic rapid ventricular pacing. Baroreflex control of the heart rate was depressed in the dogs with heart failure, as evidenced by a reduced slope of the blood pressure-to-heart rate relationship (controls: -2.5 +/- 0.3 beats/mm Hg versus heart failure: -1.5 +/- 0.2 beats/mm Hg [(p less than 0.04)]). Arterial blood pressure in the dogs with heart failure was also reduced (controls: 90 +/- 3 mm Hg versus heart failure: 75 +/- 3 mm Hg [(p less than 0.01)]). Nevertheless, dogs with heart failure exhibited normal slopes of the blood pressure versus hind limb vascular resistance relationship (controls: -2.4 +/- 0.4 units/mm Hg versus heart failure: -2.9 +/- 0.5 units/mm Hg [(p = NS)]), consistent with preserved baroreflex control of the peripheral vasculature. These data suggest that heart failure impairs arterial baroreflex control of heart rate and lowers the baroreflex pressure operating range but does not alter baroreflex control of peripheral resistance.     

Biological characterization and chemokine receptor usage of HIV type 1 isolates prevalent in Brazil

The human immunodeficiency virus type 1 (HIV-1), the etiological agent of the acquired immunodeficiency syndrome (AIDS), shows a variety of biological properties, which may constitute an obstacle to development of effective vaccines or antiretroviral therapy. To characterize Brazilian strains of HIV-1, we studied 24 viruses isolated from blood samples of HIV-1-positive patients from different regions of the country. To examine the cell tropism and the virus ability to form syncytia, primary macrophages and the CD4+ T cell line MT-2 were infected with these viruses. We found that 22 isolates replicated well in macrophages (macrophage-tropic isolates), 2 infected only MT-2 cells (T cell line tropic variants), while 6 of them grew in both cells. We found 8 syncytium-inducing (SI) and 16 non-SI (NSI) isolates. Continuous cultures of 18 isolates were established in the CCR5+/CXCR4+ cell line PM-1, and SI/NSI features of these viruses were confirmed by cell fusion assay with uninfected CD4+ T cell lines (PM-1, MT-2, H9, and SUP-T1). The coreceptor usage of 18 isolates was investigated by infecting U87 cells transfected with CD4 and chemokine receptors, and we found that 11 isolates infected only CCR5+ cells, 3 only CXCR4+ cells, whereas 4 used both coreceptors. We also observed that X4 isolates were more sensitive to neutralization by dextran sulfate than R5 or R5X4 viruses. Our findings show that the Brazilian isolates are phenotypically similar to those prevalent in other regions, which could mean that therapeutic strategies based on HIV-1 phenotypic properties would be efficient in Brazil, as in other countries.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

Career and Family Aspirations of Female Athletic Trainers Employed in the National Collegiate Athletic Association Division I Setting

Context:Female athletic trainers (ATs) tend to depart the profession of athletic training after the age of 30. Factors influencing departure are theoretical. Professional demands, particularly at the collegiate level, have also been at the forefront of anecdotal discussion on departure factors.Objective:To understand the career and family intentions of female ATs employed in the collegiate setting.Design:Qualitative study.Setting:National Collegiate Athletic Association Division I.Results:Our participants indicated a strong desire to focus on family or to start a family as part of their personal aspirations. Professionally, many female ATs were unsure of their longevity within the Division I collegiate setting or even the profession itself, with 2 main themes emerging as factors influencing decisions to depart: family planning persistence and family planning departure. Six female ATs planned to depart the profession entirely because of conflicts with motherhood and the role of the AT. Only 3 female ATs indicated a professional goal of persisting at the Division I setting regardless of their family or marital status, citing their ability to maintain work-life balance because of support networks. The remaining 17 female ATs planned to make a setting change to balance the roles of motherhood and AT because the Division I setting was not conducive to parenting.Conclusions:Our results substantiate those of previous researchers, which indicate the Division I setting can be problematic for female ATs and stimulate departure from the setting and even the profession.Key Words: retention, attrition, work-life balance

Key Points

• Female athletic trainers decided to depart the Division I setting because the required hours of the job limited the time available for parenting.
• Female athletic trainers working in the Division I setting who were able to persist after having a family credit strong support networks and the development of effective work-life balance strategies.

Traditionally, working women endure more challenges balancing career demands and family responsibilities than working men, often because of their mothering philosophies and traditional gender stereotypes.¹ Surprisingly, gender differences have not been found in the occurrence of conflicts between work and life in the athletic training profession.^2,3 This finding is perplexing because female athletic trainers (ATs) continue to depart from the profession.⁴ Hypothetically, the decline in the number of female ATs in the profession has been linked to the desire to strike a balance among work responsibilities, personal interests, and family obligations.^1–3,5Concerns about work-life balance (WLB) and time for parenting have been found to influence decisions to persist within the collegiate levels, as the job responsibilities often include long hours (>40 h/wk) and travel, which can limit time spent at home with family.^1–3,5 It is an unfortunate reality that female ATs make up only approximately 28% of the full-time collegiate staff.⁵ This is especially concerning when the National Athletic Trainers'' Association indicates that more than 50% of its members are female.⁶ A relationship appears to exist between balancing professional responsibilities with parenthood and retention factors, especially for those who leave the collegiate clinical setting to work in clinical settings more favorable to family life.Female ATs in the National Collegiate Athletic Association Division I setting experience great challenges in maintaining WLB because of the demands of the setting.¹ In a recent study,¹ the primary reasons female ATs continued in the Division I setting were enjoyment of the job and atmosphere, increased autonomy, positive athlete dynamics, and the social support network. It is important for female ATs to have support at work and home to persist in the collegiate or athletic training clinical setting. However, long work hours and the inability to find WLB can stress this support network. Mazerolle and colleagues^2,3 first proposed that motherhood plausibly could lead to departure from the profession as the result of a myriad of factors but mostly because of a lack of time and control over work schedules. Further investigations have supported this theory and also have found that other reasons for leaving the profession are WLB concerns, supervisory and coach conflicts, caring for children, and role overload.^1,4,5Fulfillment of WLB is an important retention factor for female coaches within the collegiate setting,⁷ thus providing some supporting evidence to the suppositions that motherhood can be a mediating factor in the retention of female ATs in the collegiate setting. Additional support can be garnered from Mazerolle et al,² who found that only 22 female ATs with children were employed at the collegiate setting, a statistic supported by Kahanov et al,⁵ who reported that only about a quarter of all full-time ATs at the collegiate setting were female.Concerns about retention, particularly of female ATs, have become an increasingly popular topic within the athletic training literature, with attention focused on the collegiate clinical setting. This setting not only is one of the largest employment settings for the AT⁶ but is recognized as a time-intensive, demanding work environment.^2,3,8,9 Moreover, data suggest women are leaving this particular clinical setting to find a more family-friendly work environment, which may or may not be in the profession of athletic training.^10,11 Additionally, 2 recent studies^10,11 suggest that female athletic training students intend to pursue careers in athletic training, but as highlighted by Kahanov and Eberman,⁴ women are rapidly departing the profession for a variety of reasons. The emigration of female ATs from the profession has been theoretically associated with the desire to attain balance among family commitments, personal time, and work responsibilities.^1,2 Difficulties maintaining WLB and sufficient time for parenting shape decisions to continue at the collegiate level.^1,2Because of the concerning trend of female AT attrition, the purpose of our study was to understand the perspectives of female ATs, regardless of marital status, and to evaluate career and family intentions. Our objective was to gain a more thorough understanding of female ATs'' professional goals as they may be influenced by family planning. Our research questions included, “What factors influence the career intentions of female ATs regarding career longevity?” and “Do female ATs have intentions to remain in the NCAA Division I setting?”     

Cancer‐like metabolism of the mammalian retina

The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina.