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.     

Lateral closed wedge osteotomy for cubitus varus deformity

Background:

Lateral closed wedge (LCW) osteotomy is a commonly accepted method for the correction of the cubitus varus deformity. The fixation of osteotomy is required to prevent loss of correction achieved. The fixation of the osteotomy by the two screw and figure of eight wire is not stable enough to maintain the correction achieved during surgery. In this prospective study we supplemented the fixation by Kirschner''s (K-) wires for stable fixation and evaluated the results.

Materials and Methods:

Twenty-one cases of the cubitus varus deformity following supracondylar fractures of the humerus were operated by LCW osteotomy during February 2001 to June 2006. The mean age of the patients at the time of corrective surgery was 8.5 years (range 6.6-14 years). The osteotomy was fixed by two screws with figure of eight tension band wire between them and the fixation was supplemented by passing two to three K-wires from the lateral condyle engaging the proximal medial cortex through the osteotomy site.

Result:

The mean follow-up period was 2.5 years (range seven months to 3.4 years). The results were assessed as per Morrey criteria. Eighteen cases showed excellent results and three cases showed good results. Two cases had superficial pin tract infection.

Conclusion:

The additional fixation by K wires controls rotational forces effectively besides angulation and translation forces and maintains the correction achieved peroperatively.     

Familial clustering of epilepsy and behavioral disorders: evidence for a shared genetic basis

Purpose: To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders. Methods: We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first‐degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9‐year follow‐up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)–Oriented scales were examined. The association between first‐degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first‐degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations. Key Findings: In probands with uncomplicated epilepsy, first‐degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM‐Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM‐Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first‐degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First‐degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy. Significance: Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.     

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.     

Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors

Malignant mesothelioma is an aggressive neoplastic proliferation derived from cells lining serosal membranes. The biological and clinical characteristics of epithelial type malignant mesothelioma are distinct from those of biphasic and sarcomatous type tumors. The goal of our study was to examine the molecular basis for this distinction. Microarray analysis confirmed that the molecular signatures of epithelial and biphasic histologic subtypes were distinct. Among the differentially expressed functional gene categories was the ubiquitin-proteasome pathway, which was upregulated in biphasic tumors. Cytotoxicity experiments indicated that 211H cells derived from biphasic tumors were synergistically sensitive to sequential combination regimens containing the proteasome inhibitor bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of epithelial tumor origin, was apoptosis. Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients.     

Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors

Successful immunotherapy of established tumors depends on overcoming the suppressive influence of the local tumor microenvironment. The direct injection of vaccinia virus expressing the B7.1 (CD80) costimulatory molecule into melanoma lesions resulted in local and systemic immunity with associated clinical responses. Therefore, we sought to evaluate the effects of a vaccinia virus expressing three costimulatory molecules, B7.1, ICAM-1, and LFA-3 (rV-TRICOM), in patients with metastatic melanoma. A standard dose escalation phase I clinical trial was performed. Thirteen patients were enrolled and 12 were available for follow-up. Local vaccination was feasible, with only low-grade injection site reactions associated with mild fatigue and myalgia reported. There was one occurrence of grade 1 vitiligo. Overall there was a 30.7% objective clinical response, with one patient achieving a complete response for more than 22 months. An inverse association was detected between anti-vaccinia antibody and anti-vaccinia T cell responses. Patients who failed to respond to vaccination but received high-dose interleukin-2 had a trend toward improved survival. Collectively, these results confirm the safety profile and feasibility of direct injection of vaccinia virus expressing multiple costimulatory molecules in patients with established tumors. Further clinical investigation is needed to better define the role of antigen, adjuvant cytokines, costimulation, and cross-presentation in the host immune response to local vaccination with vaccinia viruses expressing immunomodulatory molecules.