Back pain and leg complaints that revealed non–small cell carcinoma: a case study

Objective

The purpose of this case study is to describe the clinical presentation of a patient with a chief complaint of low back and leg pain with no prior diagnosis of lung cancer.

Clinical Features

A 48-year-old man with a history of back pain presented to a chiropractic office with a complaint of low back and left leg pain.

Intervention and Outcome

Abnormal examination and radiographic findings were discovered. The patient was immediately referred to the pulmonologist for co-management. Through the use of advanced imaging and biopsy, stage 4 lung cancer was diagnosed.

Conclusion

Low back pain recurrence in an established patient should constitute a reevaluation of the problem. The cause cannot be assumed to be musculoskeletal in origin even though this may have been the case with the initial complaint. Metastatic disease should be considered with any type of recurrent low back pain.     

Human subject rear passenger symptom response to frontal car-to-car low-speed crash tests

Objective

The purpose of this study was to determine whether healthy adult volunteers report symptoms following exposure to low-speed frontal crashes at low velocities.

Methods

Nineteen medically screened, healthy, informed, and willing volunteers (17 men, 2 women; mean age, 37 years) were exposed to low-speed frontal crashes. All volunteers were seated in the rear seat position of the bullet vehicle. Closing velocities ranged from 4.1 to 8.3 mph (mean, 6.7 mph). For the bullet vehicle, the delta V ranged from 1.4 to 3.9 mph with a mean of 2.8 mph.

Results

Eighty-eight percent of volunteers attributed symptoms of discomfort to their crash exposure. All reported symptoms were transient, and none required medical treatment. The mean duration was 1 day.

Conclusions

Even at relatively low speeds, there is no lower threshold below which it can be reasonably assumed that healthy and prepared volunteer rear seat passengers will not sustain some level of minor injury in a frontal collision. Although the reported mean delta V for injured persons in real-world frontal crashes has been reported to be as high as 8.1 mph, this does not offer any insight into the minimum threshold for such injuries among all at-risk vehicle occupants.     

An immunodominant SSX-2-derived epitope recognized by CD4+ T cells in association with HLA-DR

Ectopic gene expression in tumors versus normal somatic tissues provides opportunities for the specific immunotargeting of cancer cells. SSX gene products are expressed in tumors of different histological types and can be recognized by tumor-reactive CTLs from cancer patients. Here, we report the identification of an SSX-2-derived immunodominant T cell epitope recognized by CD4(+) T cells from melanoma patients in association with HLA-DR. The epitope maps to the 37-58 region of the protein, encompassing the sequence of the previously defined HLA-A2-restricted immunodominant epitope SSX-2(41-49). SSX-2(37-58)-specific CD4(+) T cells were detected among circulating lymphocytes from the majority of melanoma patients analyzed and among tumor-infiltrating lymphocytes, but not in healthy donors. Together, our data suggest a dominant role of the 37-58 sequence in the induction of cellular CD4(+) T cell responses against SSX antigens and will be instrumental for both the onset and the monitoring of upcoming cancer-vaccine trials using SSX-derived immunogens.     

Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone

BACKGROUND: The collection of adequate numbers of neutrophils (polymorphonuclear leukocytes, PMNs) from normal donors has long hampered the development of neutrophil transfusion therapy. The stimulation of donors with granulocyte-colony-stimulating factor (G- CSF) plus dexamethasone is a promising way of improving PMN collections. STUDY DESIGN AND METHODS: Sixteen normal subjects received G-CSF (600 micrograms subcutaneously) and dexamethasone (8 mg by mouth) 12 hours before leukapheresis. Measurements included PMN morphology, immunophenotype analysis, chemiluminescence, bactericidal activity, in vivo kinetics, and adverse effects. RESULTS: A mean of 77.4 +/− 6.4 × 10(9) PMNs was collected with each leukapheresis; 14 percent were bands. PMNs had increased surface expression of CD11b, CD18, CD14, CD32, and CD64. Bactericidal capacity against Staphylococcus aureus was normal. Inducible respiratory burst was maintained, although the responses to some agonists were diminished. Returned leukapheresis cells labeled with 3H-diisopropylfluorophosphate had a modestly decreased percentage of recovery and circulated with a prolonged half- life. Migration of these cells to skin chambers was approximately equal to that of the subjects' own blood PMNs. Adverse effects included transient bone pain, headache, hunger, and insomnia. CONCLUSIONS: Precollection treatment of leukapheresis donors with G-CSF plus dexamethasone is an effective way to enhance the collection of PMNs with normal or near-normal functional properties for PMN transfusion therapy.     

Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma

In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15-68 years) with poor-risk non-Hodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m2) and escalating dose mitoxantrone (30-50 mg/m2) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m2), carboplatin (800 mg/m2), and escalating dose etoposide phosphate (400-850 mg/m2), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26-120). The maximum tolerated dose was determined as 40 mg/m2 for mitoxantrone and 550 mg/m2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52-81%) and 45%, (95% CI, 29-61%) for the 41 patients enrolled; and 69% (95% CI, 525-586%) and 48% (95% CI, 30-67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined.     

Human platelet glycoprotein V: its role in enhancing expression of the glycoprotein Ib receptor

Platelet adhesion to an injured blood vessel wall is a critical initiating step in hemostasis mediated by a four member receptor complex (glycoprotein Ib/V/IX) interacting with plasma von Willebrand factor (vWF). The function of the GPV subunit within this complex is presently undefined. To study the role of glycoprotein (GP) V within the GPIb receptor complex, we transfected the GPV subunit gene into a hematopoietic cell line that constitutively expresses the other three subunits (human erythroleukemia [HEL] cells). Using flow cytometry, we found transfected GPV was surface expressed in HEL cells; this, in turn, led to increased surface expression of the ligand-binding GPIb alpha and GPIX subunits. Radioligand binding assays showed that GPV- transfected HEL cells bound more vWF than their non- or mock- transfected counterparts. We employed confocal microscopy of GPV- transfected HEL cells to show that GPV colocalizes with GPIb alpha on the cell surface. These findings suggest that the GPV subunit plays a role within the GPIb receptor complex by enhancing Ib alpha surface expression.     

骨髓干细胞动员治疗脑缺血损伤

学术背景：近来的研究表明，来源于骨髓的干细胞具有横向分化潜能和成神经分化特性，对脑缺血损伤后神经功能恢复和神经细胞的修复具有保护作用。 目的：通过回顾近年来骨髓干细胞动员对脑缺血损伤保护作用的文献，对骨髓干细胞的特性及动员过程、途经,可能的作用机制、影响因素进行阐述，以期完善骨髓干细胞动员防治脑缺血损伤的基础与临床研究。 检索策略：应用计算机检索Medline1997—01／2007—01与骨髓干细胞动员和脑缺血相关的文章。检索词“bone marrow stem cells，cerebral ischemia”并限定语言种类为English，同时计算机检索CNKI数据库1997—01／2007—01相关文章，并限定文章语言种类为中文，检索词为“骨髓干细胞，脑缺血”。就检索到的300余篇文献进行筛选，选择以骨髓干细胞动员和脑缺血损伤的基础研究为主要内容的文献63篇，其中研究内容相似的，以近5年且发表在较权威杂志者优先。 文献评价：将入选的30篇文献进行分类，11篇研究骨髓干细胞的生物学特性，19篇与骨髓干细胞动员治疗脑缺血损伤的过程．途经,可能的作用机制、影响因素相关。 资料综合：来源于骨髓的干细胞具有很强的“可塑性”，自我更新和高度增殖能力，其可能通过修复和替代脑缺血损伤后的神经细胞，促进或直接参与缺血区新生血管生成，分泌神经营养因子等，对脑缺血损伤后神经功能恢复发挥保护作用，其作用机制和作用方式目前尚不确切，有待于建立完整的动物模型技术平台，通过基础研究进行解决。 结论：骨髓干细胞对脑缺血损伤具有修复作用，采用骨髓干细胞动员的干预策略，方法简便、安全有效,无创伤且可避免干细胞移植的免疫排斥反应，具有较好的发展潜力，有望成为治疗脑缺血性疾病的研究重点。     

Randomized trial of low-dose interleukin-2 vs cyclosporine A and interferon-gamma after high-dose chemotherapy with peripheral blood progenitor support in women with high-risk primary breast cancer

High-risk primary breast cancer patients treated with high-dose chemotherapy (HDC) and stem cell support (SCS) have shown prolonged disease-free survival (DFS) in many studies; however, only one trial has demonstrated an overall survival benefit (OS). We hypothesize that the period following myeloablative therapy is ideal for immunologic manipulation and studied the effects of two different methods of immunotherapy following HDC with SCS aimed at the window of immune reconstitution. Seventy-two women with high-risk stage II or III breast cancer were randomized following HDC to receive either interleukin 2 (IL-2) at 1 million units/m(2) SQ daily for 28 days or combined cyclosporine A (CsA) at 1.25 mg/kg intravenously daily from day 0 to +28 and interferon gamma (IFN-gamma) 0.025 mg/m(2) SQ every 2 days from day +7 to +28. At a median follow-up of 67 months, no significant difference was observed in DFS or OS between the two treatment groups. The IL-2 arm had a 59% DFS (95% CI (0.45, 0.78)) and a 72% OS (95% CI (0.58, 0.88)) at 5 years. The CsA/INF-gamma arm had a similar outcome with a 55% DFS (95% CI (0.40, 0.76)) and a 78% OS (95% CI (0.65, 0.94)) at 5 years. Treatment was well tolerated, without increased toxicity.