Soluble interleukin 2 receptor in lung cancer. An indirect marker of tumor activity?

Circulating levels of the soluble interleukin 2 receptor (sIL-2R) could provide an in vivo measure of the immunologic response to human tumors. We performed a total of 326 sIL-2R serum assays in 126 patients with lung cancer (67 at diagnosis, 59 during and after treatment), 112 patients with pulmonary benign diseases, and 63 voluntary healthy subjects. Patients with lung cancer had a median value of sIL-2R of 791 U/ml, which was superior to that of both controls (398 U/ml, p less than 0.001) and patients with noninflammatory benign diseases (583 U/ml, p less than 0.02). However, infectious pulmonary disorders, such as tuberculosis and pneumonia, were associated with the highest values of the substance (median, 1150 U/ml; p less than 0.001). At the diagnosis of lung cancer, sIL-2R correlated neither with the stage of disease nor with the cell type. On the contrary, posttreatment levels of the receptor were significantly related to disease status (RO = .41, p less than 0.002), particularly in the subgroup of nonsurgical patients (RO = .48, p less than 0.001). Patients with abnormal sIL-2R levels had a nearly significant reduction in survival as compared with patients with normal values (p less than 0.1). Measurements of sIL-2R could be useful in monitoring patients under treatment for bronchogenic carcinoma, as well as in prognostication. In this setting, sIL-2R might open a new class of biologic markers, providing information that is complementary to those of the more classic tumor-derived markers.     

Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1

CD9 (p24) and PECAM1 (CD31) antigens are well-defined components of the platelet plasma membrane. Both are integral glycoproteins (GPs) implicated in the adhesive and aggregative properties of human platelets. In the present report, we have investigated their subcellular localization using immunoelectron microscopy. The monospecificity of the two polyclonal antibodies used was confirmed by immunoblotting. On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system. Some labeling was also consistently found on the alpha-granule limiting membrane. This was confirmed by double labeling experiments in which fibrinogen and von Willebrand factor (vWF) were used as alpha-granule markers. CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix. CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor. To rule out a cross-reactivity of the two polyclonal antibodies with GPIIb/IIIa, we studied PECAM1 and CD9 expression on the platelets from a patient with type I Glanzmann's thrombasthenia whose platelets are devoid of GPIIb/IIIa. The same pattern of labeling was observed for both antigens as for normal platelets. Normal platelets were further observed after stimulation by agonists that either fail to induce (ADP) or induce granule secretion (thrombin). After treatment with ADP, platelets changed shape and centralized their granules; the plasma membrane immunolabeling remained unchanged; and gold particles were still found decorating the periphery of the centralized alpha- granules. After thrombin treatment, alpha-granules fused with the platelet membrane and secretion occurred. A significant increase of labeling was then observed on the platelet surface. From these results we conclude that the alpha-granule membrane contains two additional receptors in common with the plasma membrane. This suggests that alpha- granule membrane receptors may originate from a dual mechanism: direct targeting from the Golgi complex in megakaryocytes (for alpha-granule- specific receptors such as P-selectin) or by endocytosis from the plasma membrane (for proteins distributed in the two compartments).     

Selecting the best and brightest: A comparison of residency match processes in the United States and Canada

BACKGROUND:

Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.

METHODS:

A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.

RESULTS:

Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.

CONCLUSION:

Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures.     

Gender differences on benefits and risks associated with oral antithrombotic medications for coronary artery disease

Introduction: Despite the significant advances in the pharmacological and interventional management of patients with cardiovascular disease (CVD) over the last decades, cardiovascular mortality remains the leading cause of death. Large randomized clinical trials have investigated the efficacy and safety of different antithrombotic medications in patients with CVD. Although female gender is generally underrepresented in these clinical trials, most analyses clearly indicate that both men and women may accrue therapeutic benefits from antithrombotic management strategies.

Areas covered: This review aims to provide a comprehensive and focused update on gender-related comparative clinical studies of antithrombotic therapies in patients suffering from CVD.

Expert opinion: Current evidence supports the understanding of a similar therapeutic effect between genders with signals of an increased risk of bleeding in women. However, important gaps in evidence exist due to the overall limited percentage of women that have been enrolled in randomized controlled trials. A greater awareness of gender-related issues in antithrombotic therapy should be promoted among physicians and further evidence from large clinical trials looking at the safety and efficacy balance of different antithrombotic strategies in women is warranted.     

Own or dam’s genotype? Classical colony breeding may bias spontaneous and stress-challenged activity in DAT-mutant rats

There is considerable interest in understanding what makes an individual vulnerable or resilient to the deleterious effects of stressful events. From candidate genes, dopamine (DA) and dopamine transporter (DAT) have been linked to anxiety, depression, and post-traumatic stress disorder. We investigated role of DAT using the new DAT heterozygous (DAT-HET) and homozygous mutant (DAT-KO) rat models of hyperdopaminergia. We studied the impact of two breeding conditions in spontaneous locomotor behavior of female rats. The classical colony, through mating DAT-HET males × DAT-HET females (breeding HET–HET), was used. A second WT colony was derived and maintained (breeding WT–WT). Additionally, a subgroup of rats was bred through mating DAT-KO males × WT females (atypical HET, breeding KO–WT). We studied the effects of genotype and its interaction with maternal care (depending by breeding condition). HET–HET breeding led to reduced activity in HET females compared to WT rats (from WT–WT breeding). However, HET females from KO–WT breeding did not differ so much from WT rats (WT–WT breeding). The maternal-care impact was then confirmed: HET mothers (breeding HET–HET) showed reduced liking/grooming of pups and increased digging away from nest, compared to WT mothers (breeding WT–WT). In their female offspring (HET, breeding HET–HET vs. WT, breeding WT–WT), isolation plus wet bedding induced higher and more persistent impact on activity of HET rats, even when the stressor was removed. Our results highlight the importance of epigenetic factors (e.g., maternal care) in responses to stress expressed by offspring at adulthood, quite independently of genotype. DAT hypofunction could determinate vulnerability to stressful agents via altered maternal care.