Prognosis of refractory neurosarcoidosis altered by thalidomide: a case report

Introduction: Sarcoidosis is a multisystem disease characterized by noncaseating granulomas in the lungs, skin, lymph nodes, and, rarely, the nervous system. Granuloma formation in sarcoidosis is mediated by increased secretion of interferon-gamma, interleukin-2, and tumor necrosis factor-alpha. 25% of patients with neurosarcoidosis are steroid resistant and another 20–40% are resistant to any conventional immunosuppression, but the typical agents suppress the immune system in a non-specific fashion. Thalidomide has been shown to have activity specific to the inflammatory mediators of sarcoidosis, has been shown to be beneficial in cutaneous sarcoidosis, and provides an interesting observation in our patient with refractory neurosarcoidosis. Case presentation: A 40 year old African-american female presented with refractory neurosarcoidosis. Over the course of several years, the patient was treated with high dose steroids, imuran, cytoxan, and cyclosporine without benefit. Then, the patient received thalidomide, slowly escalating to 650 mg. After 2 months radiologic improvement was noted and after 6 months clinical stabilization and improvement became apparent. Conclusion: Our case report presents a difficult, refractory case of neurosarcoidosis that demonstrates an altered prognosis based on the addition of thalidomide

Racial/Ethnic Disparities in Knowledge about Risks and Benefits of Breast Cancer Treatment: Does It Matter Where You Go?

To evaluate the association between provider characteristics and treatment location and racial/ethnic minority patients' knowledge of breast cancer treatment risks and benefits. Data Sources/Data Collection . Survey responses and clinical data from breast cancer patients of Detroit and Los Angeles SEER registries were merged with surgeon survey responses ( N =1,132 patients, 277 surgeons). Study Design . Cross-sectional survey. Multivariable regression was used to identify associations between patient, surgeon, and treatment setting factors and accurate knowledge of the survival benefit and recurrence risk related to mastectomy and breast conserving surgery with radiation. Principal Findings . Half (51 percent) of respondents had survival knowledge, while close to half (47.6 percent) were uncertain regarding recurrence knowledge. Minority patients and those with lower education were less likely to have adequate survival knowledge and more likely to be uncertain regarding recurrence risk than their counterparts ( p <.001). Neither surgeon characteristics nor treatment location attenuated racial/ethnic knowledge disparities. Patient–physician communication was significantly ( p <.001) associated with both types of knowledge, but did not influence racial/ethnic differences in knowledge. Conclusions . Interventions to improve patient understanding of the benefits and risks of breast cancer treatments are needed across surgeons and treatment setting, particularly for racial/ethnic minority women with breast cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71991/1/j.1475-6773.2008.00843.x.pd

Translation Initiation Rate Determines the Impact of Ribosome Stalling on Bacterial Protein Synthesis

Ribosome stalling during translation can be caused by a number of characterized mechanisms. However, the impact of elongation stalls on protein levels is variable, and the reasons for this are often unclear. To investigate this relationship, we examined the bacterial translation elongation factor P (EF-P), which plays a critical role in rescuing ribosomes stalled at specific amino acid sequences including polyproline motifs. In previous proteomic analyses of both Salmonella and Escherichia coli efp mutants, it was evident that not all proteins containing a polyproline motif were dependent on EF-P for efficient expression in vivo . The α- and β-subunits of ATP synthase, AtpA and AtpD, are translated from the same mRNA transcript, and both contain a PPG motif; however, proteomic analysis revealed that AtpD levels are strongly dependent on EF-P, whereas AtpA levels are independent of EF-P. Using these model proteins, we systematically determined that EF-P dependence is strongly influenced by elements in the 5′-untranslated region of the mRNA. By mutating either the Shine-Dalgarno sequence or the start codon, we find that EF-P dependence correlates directly with the rate of translation initiation where strongly expressed proteins show the greatest dependence on EF-P. Our findings demonstrate that polyproline-induced stalls exert a net effect on protein levels only if they limit translation significantly more than initiation. This model can be generalized to explain why sequences that induce pauses in translation elongation to, for example, facilitate folding do not necessarily exact a penalty on the overall production of the protein

Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End Results registry data

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) registry data have been used to suggest underuse and disparities in receipt of radiotherapy. Prior studies have cautioned that SEER may underascertain radiotherapy but lacked adequate representation to assess whether underascertainment varies by geography or patient sociodemographic characteristics. The authors sought to determine rates and correlates of underascertainment of radiotherapy in recent SEER data. METHODS: The authors evaluated data from 2290 survey respondents with nonmetastatic breast cancer, aged 20 to 79 years, diagnosed from June of 2005 to February 2007 in Detroit and Los Angeles and reported to SEER registries (73% response rate). Survey responses regarding treatment and sociodemographic factors were merged with SEER data. The authors compared radiotherapy receipt as reported by patients versus SEER records. The authors then assessed correlates of radiotherapy underascertainment in SEER. RESULTS: Of 1292 patients who reported receiving radiotherapy, 273 were coded as not receiving radiotherapy in SEER (underascertained). Underascertainment was more common in Los Angeles than in Detroit (32.0% vs 11.25%, P < .001). On multivariate analysis, radiotherapy underascertainment was significantly associated in each registry (Los Angeles, Detroit) with stage ( P = .008, P = .026), income ( P < .001, P = .050), mastectomy receipt ( P < .001, P < .001), chemotherapy receipt ( P < .001, P = .045), and diagnosis at a hospital that was not accredited by the American College of Surgeons ( P < .001, P < .001). In Los Angeles, additional significant variables included younger age ( P < .001), nonprivate insurance ( P < .001), and delayed receipt of radiotherapy ( P < .001). CONCLUSIONS: SEER registry data as currently collected may not be an appropriate source for documentation of rates of radiotherapy receipt or investigation of geographic variation in the radiation treatment of breast cancer. Cancer 2011;. © 2011 American Cancer Society. This study found that the Los Angeles Cancer Surveillance Program, among the largest Surveillance, Epidemiology, and End Results (SEER) registries, coded that radiation was not received in nearly a third of cases in which breast cancer patients themselves reported radiation receipt, whereas ascertainment of radiation receipt was much more complete in another large SEER registry, that of the Metropolitan Detroit Cancer Surveillance System. SEER registry data as currently collected may not be an appropriate source for documentation of rates of radiotherapy receipt or geographic disparities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90319/1/26295_ftp.pd

Informal Caregiving for Diabetes and Diabetic Complications Among Elderly Americans

Objectives: Little is known regarding the amount of time spent by unpaid caregivers providing help to elderly individuals for disabilities associated with diabetes mellitus (DM). We sought to obtain nationally representative estimates of the time, and associated cost, of informal caregiving provided to the elderly with diabetes, and to determine the complications of DM that contribute most significantly to the subsequent need for informal care. Methods: We estimated multivariable regression models using data from the 1993 Asset and Health Dynamics (AHEAD) Study, a nationally representative survey of people aged 70 or older (N=7,443), to determine the weekly hours of informal caregiving and imputed cost of caregiver time for community-dwelling elderly with and without a diagnosis of DM. Results: Those without DM received an average of 6.1 hours per week of informal care, those with DM taking no medications received 10.5 hours, those with DM taking oral medications received 10.1 hours, and those with DM taking insulin received 14.4 hours of care (P

The effect of single-dose tramadol on oxycodone clearance.

We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance